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The Nobel Foundation

The Nobel Foundation is a private institution established in 1900 based on the will of Alfred Nobel. The Foundation manages the assets made available through the will for the awarding of the Nobel Prize in Physics, Chemistry, Physiology or Medicine, Literature and Peace. It represents the Nobel Institutions externally and administers informational activities and arrangements surrounding the presentation of the Nobel Prize. The Foundation also administers the Nobel Symposium Program.

Background and Establishment of the Nobel Foundation Alfred Nobel died on December 10, 1896. The provisions of his will and their unusual purpose, as well as their partly incomplete form, attracted great attention and soon led to skepticism and criticism, also aimed at the testator due to his international spirit. Only after several years of negotiations and often rather bitter conflicts, and after various obstacles had been circumvented or overcome, could the fundamental concepts presented in the will assume solid form with the establishment of the Nobel Foundation. On April 26, 1897, the Storting (Norwegian Parliament) approved the will and soon afterwards elected members to the prize-awarding Norwegian Nobel Committee of the Storting. In 1898 the other prize-awarding bodies followed suit, approving the will after mediation: Karolinska Institutet on June 7, the Swedish Academy on June 9 and the Royal Swedish Academy of Sciences on June 11.

The testator and his will. The superimposed photo of Alfred Nobel was taken in 1896, the year he died.

The will was now settled. The task of achieving unity among all the affected parties on how to put its provisions into practice remained. The final version of the Statutes of the Nobel Foundation contained clarifications of the wording of the will and a provision that prizes not considered possible to award could be allocated to funds that would otherwise promote the intentions of the testator. The Statutes provided for the establishment of Nobel Committees to perform prize adjudication work and Nobel Institutes to support this work, as well as the appointment of a Board of Directors in charge of the Foundation's financial and administrative management.

On June 29, 1900, the Statutes of the newly created legatee, the Nobel Foundation, and special regulations for the Swedish Prize-Awarding Institutions were promulgated by the King in Council (Oscar II). The same year as the political union between Sweden and Norway was dissolved in 1905, special regulations were adopted on April 10, 1905, by the Nobel Committee of the Storting (known since January 1, 1977 as the Norwegian Nobel Committee), the awarder of the Nobel Peace Prize.

A century old. The cover of the Statutes of the Nobel Foundation when it was promulgated on June 29, 1900.

Premises To create a worthy framework around the prizes, the Board decided at an early stage that it would erect its own building in Stockholm, which would include a hall for the Prize Award Ceremony and Banquet as well as its own administrative offices. Ferdinand Boberg was selected as the architect. He presented an ambitious proposal for a Nobel Palace, which generated extensive publicity but also led to doubts and questions. World War I broke out before any decision could be made. The proposal was "put on ice" and by the time the matter was revived after the war, Ivar Tengbom was busily designing what later became the Stockholm Concert Hall. Meanwhile the Stockholm City Hall was being built under the supervision of Ragnar Östberg. Boberg, Tengbom, and Östberg were probably the most respected architects in Sweden at that time. Because it would have access to both these buildings for its events, the Nobel Foundation now only needed space for its administrative offices. On December 19, 1918, a building at Sturegatan 14 was bought for this purpose. After years of renovation there, the Foundation finally left its cramped premises at Norrlandsgatan 6 in 1926 and moved to Sturegatan 14, where the Foundation has been housed ever since.

Objectives of the Foundation The Nobel Foundation is a private institution. It is entrusted with protecting the common interests of the Prize Awarding Institutions named in the will, as well as representing the Nobel institutions externally. This includes informational activities as well as arrangements related to the presentation of the Nobel Prizes. The Foundation is not, however, involved in the selection process and the final choice of the Laureates (as Nobel Prize winners are also called). In this work, the Prize-Awarding Institutions are not only entirely independent of all government agencies and organizations, but also of the Nobel Foundation. Their autonomy is of crucial importance to the objectivity and quality of their prize decisions. One vital task of the Foundation is to manage its assets in such a way as to safeguard the financial base of the prizes themselves and of the prize selection process.

Statutes and Significant Amendments during 100 Years The Statutes, as most recently revised in 2000, assign roles to the following bodies or individuals in the Nobel Foundation's activities:

The Board and the Executive Director (especially paragraphs 13 and 14)

The Prize-Awarding Institutions (especially paragraphs 1 and 2)

The Trustees of the Prize-Awarding Institutions (especially paragraph 18)

The Nobel Committees and experts (especially paragraph 6)

Bodies and individuals entitled to submit prize nominations (especially paragraph 7)

Auditors (especially paragraph 19)

Over the past 100 years, there have been a number of changes in the relationship between the Foundation's Board of Directors and the Swedish State. Their links have gradually been severed.

According to paragraph 14 of the first Statutes from 1901, the Foundation was to be represented by a Board with its seat in Stockholm, consisting of five Swedish men. One of these, the Chairman of the Board, was to be designated by the King in Council. The Trustees of the Prize Awarding Institutions would appoint the others. The Board would choose an Executive Director from among its own members. An alternate (deputy) to the Chairman would be appointed by the King in Council (effective in 1974, by the Government), and two deputies for the other members would be elected by the Trustees. Since 1995 the Trustees have appointed all members and deputies of the Board. The Board chooses a Chairman, Deputy Chairman and Executive Director from among its own members.

The first Board of Directors of the Nobel Foundation was elected by the Trustees on September 27, 1900 (Hans Forsell, Ragnar Törnebladh, Henrik Santesson, and Ragnar Sohlman, with Mauritz Salin and Oscar Montelius as Deputies). On the following day, former Prime Minister Erik Gustaf Boström was appointed Chairman of the Board by the King in Council with the Justice of the Supreme Court C. G. Hernmarck as Deputy. On October 3, 1900 the Board elected Assistant Circuit Judge Henrik Santesson as the first Executive Director of the Foundation. Effective on January 1, 1901 the Board assumed management of the Foundation's assets.

Until 1960 the Chairman was chosen from the small group of "Gentlemen of the Realm" - prime ministers, ministers for foreign affairs and other high officials. In 1960 for the first time, a renowned scientist was chosen: Arne Tiselius, Professor of Biochemistry at Uppsala University and 1948 Nobel Laureate in Chemistry. Since then the Chairman has been chosen from among members of the Prize-Awarding Institutions. It has also become a rule that the Deputy Chairman as well as one of the members of the Board elected by the Trustees should be persons with financial expertise. This custom began in 1951, when senior banker and industrialist Jacob Wallenberg was elected to the Board by the Trustees. He was also a member of the Royal Swedish Academy of Sciences. When his brother Marcus Wallenberg succeeded him in 1968, it was the first time that a member of the Board did not belong to a Prize-Awarding Institution. As to the Deputy Chairman of the Board, appointed by the King in Council, this practice started in 1960, when the prominent banker Gustaf Söderlund was elected to the Board. In most cases, the Executive Director has had a legal and administrative background. As the Foundation's investment policy became more active from the early 1950s onward, financial experience coupled with a knowledge of international relations have been valuable assets for those holding this position.

Arne Tiselius was Chairman of the Board of the Nobel Foundation 1960-1964.

An important landmark in the history of the Foundation occurred when it added Norwegian representation to the Board. In 1901, the Norwegians refrained from representation on the Board - being appointed by King Oscar at a time when Norway was moving toward a breakup of its union with Sweden was not considered an attractive idea - and they limited their involvement to work as Trustees and auditors. In light of this, it is interesting to note that Henrik Santesson, the first Executive Director of the Foundation, also happened to be the legal counsel of the Storting in Sweden. But in 1986, paragraph 14 of the Statutes was changed and the Board no longer had to consist of five Swedish citizens (the original Statutes had said Swedish men), but of six Swedish or Norwegian citizens. The Statutes were also changed in such a way that remuneration to the Board members and auditors of the Foundation, as well as the salary of the Executive Director, would be determined by the Foundation's Board instead of the Swedish Government.

King Oscar II of Sweden

According to paragraph 17 of the original Statutes, the administration of the Board and the accounts of the Foundation for each calendar year were to be examined by five auditors. Each prize-awarding body would elect one of these before the end of the year and the King would designate one, who would be the chairman of the auditors. In 1955 the number of auditors was enlarged from five to six; the new auditor would be appointed by the Trustees and had to be an authorized public accountant. This was a very important change, in line with the Foundation's more active financial investment policy.

Today the Government's only role in the Nobel Foundation is to appoint one auditor, who is also to be the chairman of the Foundation's auditors.

Among other changes that have occurred in the Statutes are the following:

Until 1968, in principle more than three persons could share a Nobel Prize, but this never occurred in practice. The previous wording of paragraph 4 was: "A prize may be equally divided between two works, each of which may be considered to merit a prize. If a work which is to be rewarded has been produced by two or more persons together, the prize shall be awarded to them jointly." In 1968 this section was changed to read that "In no case may a prize be divided between more than three persons."

In 1974, the Statutes were changed in two respects. The confidential archive material that formed the basis for the evaluation and selection of candidates for the prizes, which was previously closed to all outsiders, could now be made available for purposes of historical research if at least 50 years had elapsed since the decision in question. The other change concerned deceased persons. Previously, a person could be awarded a prize posthumously if he/she had already been nominated (before February 1 of the same year), which was true of Erik Axel Karlfeldt (Literature Prize, 1931) and Dag Hammarskjöld (Peace Prize, 1961). Effective from 1974, the prize may only go to a deceased person to whom it was already awarded (usually in October) but who had died before he/she could receive the prize on December 10 (William Vickrey, 1996 Sveriges Riksbank Prize in Economic Sciences in Memory of Alfred Nobel).

Financial Management The main task of the Nobel Foundation is to safeguard the financial base of the Nobel Prizes and of the work connected to the selection of the Nobel Laureates.

In its role as a financial manager, the Nobel Foundation resembles an investment company. The investment policy of the Foundation is naturally of the greatest importance in preserving and increasing its funds, thereby ensuring the size of the Nobel Prizes. The provisions of Alfred Nobel's will instructed his executors to invest his remaining realizable estate, which would constitute the capital of what eventually became the Nobel Foundation, in "safe securities." In the original by-laws of the Board, approved by the King in Council on February 15, 1901, the expression "safe securities" was interpreted in the spirit of that time as referring mainly to bonds or loans - Swedish as well as foreign - paying fixed interest and backed by solid underlying security (central or local government, property mortgages or the like). In those days, many bonds were sold with a so-called gold clause, stipulating that the holder was entitled to demand payment in gold. The stock market and real estate holdings were beyond the pale. Stocks in particular were regarded as an excessively risky and speculative form of financial investment.

The first 50 years of management came to be characterized by rigidity in terms of financial investments and by an increasingly onerous tax burden. Remarkably, the tax issue had not been addressed when the Nobel Foundation was established. The tax-exempt status that the executors of the will and others had assumed as self-evident was not granted. Until 1914, the tax was not excessively heavy, only 10 percent, but when a "temporary defense tax" supplement was introduced in 1915, the Foundation's tax burden doubled. In 1922, a maximum tax assessment was imposed which exceeded the sum available for the prizes in 1923, the year when the Nobel Prize amount reached its absolute low point. For a long time, the Nobel Foundation was the largest single taxpayer in Stockholm. The question of granting tax-exempt status to the Foundation was debated back and forth in the Riksdag (Swedish Parliament) for years.

In 1946, when the Foundation was finally exempted from national income and wealth tax and local income tax, this allowed a gradual long-term increase in the size of the Foundation's main fund, the Nobel Prizes and the sums paid to the Prize-Awarding Institutions for their adjudication work. Without Swedish tax-exempt status, it would have been impossible for the Foundation to receive equivalent tax relief for its financial investments in the United States. In the event, a U.S. Treasury ruling granted the Foundation tax-exempt status in that country effective from 1953. Tax-exempt status created greater freedom of action, enabling the Foundation to pursue an investment policy not dominated by tax considerations that characterize the actions of many investors.

However, the restrictions on the Foundation's freedom of investments continued with minor changes until 1953, although the gold clause and resulting protection against declining value had disappeared as early as World War I. Because of two world wars and the depression of the early 1930s, the prizes shrank in real terms from SEK 150,000 in 1901 (equivalent to 20 times the annual salary of a university professor) to a mere one third of this value.

Then, in 1953, the Government approved a radical liberalization of the investment rules. The Foundation was granted a more extensive freedom to manage its capital independently, as well as the opportunity to invest in stocks and real estate. Freedom of investment, coupled with tax-exemption and the financial expertise of the Board, led to a transformation from passive to active management. This can be regarded as a landmark change in the role of the Foundation's Board. During the 1960s and 1970s, the value of the Nobel Prizes multiplied in Swedish krona terms but rapid inflation meanwhile undermined their real value, leaving each prize largely unchanged. The same was true of the Foundation's capital.

Photo of the check received by Prof. J. C. Kendrew, 1962 Nobel Chemistry Laureate. Nowadays, no checks are given. The prize money is transferred by bank according to the Laureate's wishes.

During the 1980s, the Foundation experienced a change for the better. The stock market performed outstandingly and the Foundation's real estate also climbed in value. A sour note came in 1985, when Swedish real estate taxes rose sharply and profits consequently vanished. In 1987, the Board decided to transfer most of the Foundation's real estate to a separate company called Beväringen, which was then floated on the stock exchange. In the same year that Beväringen was established, the Nobel Foundation surpassed its original value in real terms (SEK 31 million in 1901 money) for the first time. The Foundation was fortunate enough to sell its entire holding in Beväringen before the real estate crash of the early 1990s.

The first Nobel Prize in 1901 amounted to SEK 150,000, equivalent to SEK 7.4 million in 2006 money.

By 1991, the Foundation had restored the Nobel Prizes to their 1901 real value. Today the nominal fund capital of the Nobel Foundation is about SEK 3.6 billion. In 2006 each of the five Nobel Prizes as well as the Economics Prize was worth SEK 10 million (about USD 1.45 million). This is well above the nominal value of the entire original fund, and higher than the real value of the original prizes. Since January 1, 2000, the Nobel Foundation has also been permitted to apply the capital gains from the sale of assets toward the prize amounts. According to Alfred Nobel's will, only direct return - interest and dividends - could be used for the prize amounts. Capital gains from share management could not previously be used. According to the new rules, return that arises from the sale of Foundation assets may also be used for prize award events and overhead, to the extent that they are not needed to maintain a good long-term prize-awarding capacity. This change is necessary to avoid undermining the value of the Nobel Prizes. The Nobel Foundation may also decide how much of its assets may be invested in shares. In the long term, this may mean that the Foundation can now have a higher percentage of its assets invested in shares, leading to higher overall return and thus larger Nobel Prizes.

The Sveriges Riksbank Prize in Economic Sciences in Memory of Alfred Nobel On the occasion of its 300th anniversary in 1968, the Sveriges Riksbank (Sweden's central bank) made a large donation to the Nobel Foundation. A Prize in Economic Sciences in Memory of Alfred Nobel has been awarded since 1969. The Royal Swedish Academy of Sciences is entrusted with the role of Prize Awarding-Institution, in accordance with Nobel Prize rules. The Board of the Nobel Foundation has subsequently decided that it will allow no further new prizes.

The Economics Prize medal's front ... and back.

Nobel Symposia An important addition to the activities of the Nobel Foundation is its Symposium program, which was initiated in 1965 and has achieved a high international standing. Approximately 135 Nobel Symposia, dealing with topics at the frontiers of science and culture and related to the Prize categories, have taken place. In addition to these Nobel Symposia, six Nobel Jubilee Symposia were held in 1991 and six Nobel Centennial Symposia in 2001. Since 1982 the Nobel Symposia have been financed by the Foundation's Symposium Fund, created in 1982 through an initial donation from the Bank of Sweden Tercentenary Foundation and the Knut and Alice Wallenberg Foundation, as well as through grants and royalties received by the Nobel Foundation as part of its informational activities.

Donations and Prizes Around the world, new international scientific and cultural prizes have been established, directly inspired by the Nobel Prize. For example, the Japan Prize and Kyoto Prize - both financially in a class with the Nobel Prize - were established in 1985 and their statutes directly refer to the Nobel Prizes as a model and source of inspiration. Donations from these and many other sources have reached the Foundation over the years. Some of these donations are presented below.

In 1962 the Balzan Foundation, based in Switzerland and Italy, gave its first prize of one million Swiss francs to the Nobel Foundation for having awarded its Nobel Prizes for 60 years in an exemplary way, thereby celebrating "l'oeuvre admirable accomplie dans 60 années de travail."

In 1972, Georg von Békésy, 1961 Nobel Laureate in physiology or medicine, donated his exquisite collection of art objects to the Nobel Foundation - some 150 objects from four continents (not Australia). The collection is now deposited with various museums in Stockholm, mainly the Museum of Far Eastern Antiquities but also the Museum of Medieval Stockholm, the Ethnographic Museum and the National Museum.

Cover of The Georg von Békésy Collection published by the Nobel Foundation in 1974.

Also in 1972 the Foundation received a donation from the Italian marquis Luigi de Beaumont Bonelli, who bequeathed his two wine-growing estates outside Taranto, southern Italy, to the Nobel Foundation. The properties were worth SEK 4.5 million. Their sale made possible the establishment of an annual Beaumont-Bonelli fellowship to a promising young Italian medical researcher.

The two Japanese prizes were mentioned above. On April 20, 1985, the Science and Technology Foundation of Japan established the Japan Prize. At the first award ceremony, a special prize of JPY 50 million was awarded to the Nobel Foundation "in recognition of the role the Nobel Foundation has played since 1901 in promoting science and international understanding." On November 10, 1985, the Inamori Foundation in Kyoto awarded its first Kyoto Prize of JPY 45 million to the Nobel Foundation "with the aim of promoting science, technology and the arts in the spirit of the Nobel Prize."

Nobel Festivities The Nobel Foundation is an "investment company" with rather unusual facets. Every year this investment company moves into show business by organizing the Nobel Festivities and numerous related arrangements that take place in December. The Nobel Foundation is responsible for organizing the Nobel Festivities in Stockholm, while in Norway the Norwegian Nobel Committee is in charge of the corresponding arrangements. On December 10, 1901, the Nobel Prizes were awarded for the first time in Stockholm and in Christiania (now Oslo) respectively.

Stockholm The Prize Award Ceremony in Stockholm took place at the Old Royal Academy of Music during the years 1901-1925. Parenthetically, it is worth mentioning that during the first years the names of the Nobel Laureates were not made public until the Award Ceremony itself.

The first Nobel Prize Award Ceremony at the Old Royal Academy of Music in Stockholm (1901).

Since 1926, the Prize Award Ceremony has taken place at the Stockholm Concert Hall with few exceptions. In 1971 the venue was the Philadelphia Church and in 1972 the St. Erik International Fair (known today as Stockholm International Fairs) in Älvsjö, both times due to repairs at the Concert Hall. In 1975 the Ceremony again took place at the St. Erik International Fair and in 1991 at the Stockholm Globe Arena, now due to special commemorations of Nobel history that required large seating capacity. In 1975, it was the 75th anniversary of the Nobel Foundation that was being commemorated, while in 1991 the 90th anniversary of the first Nobel Prizes was the focus of the celebrations. In 1975 about 70 pre-1975 Nobel Laureates attended, and in 1991 approximately 130 pre-1991 Laureates. When the Foundation celebrated the 100th anniversary of the Nobel Prizes in 2001, the number of pre-2001 Laureates in attendance was approximately 160.

Crown Prince Carl Gustaf of Sweden (now King), hands over the 1972 Nobel Prize for Literature to Heinrich Böll during the Prize Award Ceremony at the St. Erik International Fair (known today as Stockholm International Fairs) in Älvsjö.

When the Prize Award Ceremony returned to the Concert Hall in 1973 after an absence of two years, the whole stage setting had changed. The most significant change was that the King and Queen of Sweden and other members of the Royal Family, who had previously always sat in the front row of the auditorium, were moved up and seated on one side of the stage. The Laureates sat on the other side and members of the Prize-Awarding Institutions behind them. In 1973, Carl XVI Gustaf presented the Nobel Prizes for the first time as His Majesty the King of Sweden. Once before, in 1972, owing to the illness of his grandfather King Gustaf VI Adolf, he had presented the Prizes, but in the capacity of Crown Prince. The next change in the stage at the Concert Hall was in 1992. The stage design was now changed to resemble that of the first Prize Award Ceremony held at the Stockholm Concert Hall in 1926. As in 1926, the chairs on the stage were placed in an amphitheatrical grouping. An effort was made by various means to highlight the simplicity of the room and to emphasize the academic nature of the festivities.

Prize Award Ceremony at the Concert Hall in 1926.

Nobel Prize Award Ceremony at the Stockholm Concert Hall in 1973.

The Nobel Prize Award Ceremony at the Stockholm Globe Arena in 1991.

The new stage at the Stockholm Concert Hall in 1992.

Until the early 1930s, the Nobel Banquet took place at the Hall of Mirrors in the Grand Hôtel, Stockholm. In its very first years, 1901 and 1902, the banquet was an exclusive party for men only. Once the Stockholm City Hall had been built, in 1930 a decision was made to hold the Banquet in its fantastic Golden Hall this year and in the future. For some reason the Nobel Banquets of 1931 and 1932 took place at the Grand Hôtel again, but between 1933 and 1973 it was held in the Golden Hall. Over time, the character of the Banquets changed and interest in participating became greater and greater. Starting in 1974, due to the need for more space the Nobel Banquet was moved from the Golden Hall to the larger Blue Hall of the City Hall, which today accommodates some 1,300 guests. The Blue Hall had only been used for the Banquet once before, in 1950, when the Nobel Foundation celebrated its 50th anniversary with approximately 32 pre-1950 Laureates participating.

The Nobel Banquet at the Golden Hall of the Stockholm City Hall in 1973.

The Nobel Banquet at the Blue Hall of the Stockholm City Hall in 1998. Photo: Hans Pettersson

There are always exceptions to the rules. In 1907, there were no festivities in Stockholm because the Royal Court was in mourning. King Oscar II had just died. The Laureates were awarded their prizes at a ceremony at the auditorium of the Royal Swedish Academy of Sciences. During 1914-1918 the Nobel Festivities were called off in Sweden and in Norway, except for a ceremony in 1917 at the Norwegian Nobel Institute in the presence of King Haakon to announce that the International Red Cross had been awarded the Peace Prize.

The first Nobel Prizes after the World War I - the 1919 prizes - were awarded in June the next year in order to give the Festivities an atmosphere of early Swedish summer with sunshine, light and greenery instead of dark December with cold and wet snow. The Ceremony took place on June 2, 1920 at the Royal Academy of Music, with the subsequent Banquet at the Hasselbacken restaurant near the Skansen outdoor museum. This was not a success. No members of the Royal Family were present because of the death of Crown Princess Margaretha. The weather was gray, rainy and cold. As a result of disappointment at the absence of the King, the bad weather and the questionable suitability of Hasselbacken for banquets of this kind, the Nobel Festivities of 1920 reverted to earlier tradition and were held on December 10; the Prize Award Ceremony - again attended by His Majesty the King - at the Royal Academy of Music and the Nobel Banquet at the Hall of Mirrors in the Grand Hôtel.

In 1924 the Nobel Festivities were cancelled in Stockholm. Neither of the two Laureates could be present: the Laureate in Physiology or Medicine was traveling and the Literature Laureate was unwell. The Prizes in Physics and Chemistry were reserved that year.

During the period 1939-1943, the Nobel Festivities were called off. In 1939 only the Laureate in Literature, Frans Eemil Sillanpää from Finland, received his Prize in Stockholm at a small ceremony, with a subsequent dinner at the restaurant "Den Gyldene Freden" together with the Permanent Secretary of the Swedish Academy, Anders Österling. During 1940-1942 no Physics, Chemistry or Medicine Prizes were awarded, during 1940-1943 no Literature Prizes, and during 1939-1943 no Peace Prizes.

In 1944 there were no Festivities in Stockholm, but a luncheon was held at the Waldorf-Astoria Hotel in New York organized by the American Scandinavian Foundation. Some 1943 and 1944 Laureates received their Prizes from the Swedish Minister (chief diplomat) in Washington, W. F. Boström; two Physics Laureates - Otto Stern (1943) and Isidor Isaac Rabi (1944) - and four Laureates in Physiology or Medicine - Henrik Dam and Edward Doisy (1943), and Joseph Erlanger and Herbert S. Gasser (1944). Speeches by Sweden's Crown Prince Gustaf Adolf and by Professor The Svedberg were broadcast on American radio the same day. The 1943 Laureate in Chemistry, George de Hevesy, received his Prize in Sweden without any ceremonies and the 1944 Literature Laureate, Johannes V. Jensen from Denmark, received his Prize in Stockholm in 1945.

Just before and during the war, Adolf Hitler forbade Laureates from Germany - Richard Kuhn (Chemistry, 1938), Adolf Friedrich Johan Butenandt (Chemistry, 1939) and Gerhard Domagk (Physiology or Medicine, 1939) - from accepting their Prizes at that time. However, they received their insignia on later occasions.

Guests at the Nobel Dinner at the Swedish Academy in 1956.

In 1956, due to the crisis in Hungary, a smaller, more private dinner at the Swedish Academy replaced the glittering banquet in the City Hall, although the Prize Award Ceremony took place as usual at the Concert Hall.

Christiania/Oslo In Norway, during the years 1901-1904 the decision on the Peace Prize was announced at a meeting of the Storting on December 10, after which the recipients were informed in writing. On December 10, 1905, the Nobel Institute's new building at Drammensveien 19 was inaugurated in the presence of the Norwegian Royal Couple, and it was announced that Bertha von Suttner had received the 1905 Peace Prize. The Laureate herself was not present. During 1905-1946 the Prize Award Ceremonies were held at the Nobel Institute building, during 1947-1989 in the auditorium of the University of Oslo and since 1990 at the Oslo City Hall. The King of Norway is present, but it is the Chairman of the Nobel Committee who hands over the Prize to the Laureate or Laureates. The Nobel Banquet in Norway is a dignified formal occasion, but much less pretentious than the Banquet in Stockholm. It takes place at the Grand Hôtel in Oslo, with approximately 250 guests.

The Peace Prize Award Ceremony at the Oslo City Hall.

The Norwegian Nobel Committee and the Nobel Foundation during World War II In 1940, three members of the Storting's Nobel Committee were in exile due to the occupation of Norway by Nazi Germany, which lasted until 1945. The remaining members and deputies kept the work of the Committee going. Because the Storting could not elect new Committee members, the Nobel Foundation asked existing members to continue in their posts.

In January 1944, pro-Nazi Prime Minister Vidkun Quisling and his administration wanted to take over the functions of the Nobel Committee in Norway and seize control of the Nobel Institute's building on Drammensveien. After consultations with the Swedish Foreign Ministry and the Director of the Nobel Institute, the Nobel Foundation declared that the Nobel Institute was Swedish property. Those Committee members who had remained in Norway stated in writing that under the prevailing circumstances, they could not continue their work. Sweden's consul general in Oslo, who had already moved into an office on the Nobel Institute's premises, took over the management of the building and the functions of the Nobel Institute. In 1944-1945 the Nobel Foundation (Hammarskjöld and Ekeberg) together with the members of the Nobel Committee in exile ensured that nominations were submitted for the 1945 Peace Prize.

A New Century After more than a hundred years of existence, the Nobel Prizes - as well as the centenarian Nobel Foundation - have become solid institutions, based on a great tradition since their beginning. The original criticisms aimed at the whole idea of the Nobel Prizes have faded into oblivion. Both in Sweden and in Norway, the awarding of the prizes is regarded as an event of national importance. The Nobel Foundation has now entered a new century, with museum and exhibition projects, while being able to look back at its past successes in many fields.

Biographical Accounts Alfred Nobel (1833-1896) was born in Stockholm, Sweden, on October 21, 1833. His family was descended from Olof Rudbeck, the best-known technical genius in Sweden in the 17th century, an era in which Sweden was a great power in northern Europe. Nobel was fluent in several languages, and wrote poetry and drama. Nobel was also very interested in social and peace-related issues, and held views that were considered radical during his time.

The Nobel Prize Every year since 1901 the Nobel Prize has been awarded for achievements in physics, chemistry, physiology or medicine, literature and for peace. The Nobel Prize is an international award administered by the Nobel Foundation in Stockholm, Sweden. In 1968, Sveriges Riksbank established The Sveriges Riksbank Prize in Economic Sciences in Memory of Alfred Nobel, founder of the Nobel Prize. Each prize consists of a medal, personal diploma, and a cash award.

All Nobel Peace Prize LaureatesItalic text

The Nobel Peace Prize has been awarded to 95 individuals and 20 organizations since 1901. (Comité International de la Croix Rouge was awarded the prize in 1917, 1944 and 1963; Office of the United Nations High Commissioner for Refugees was awarded the prize in 1954 and 1981.) Click on a name to go to the Laureate's page.

Jump down to: | 1980 | 1960 | 1940 | 1920 | 1901 | 2007 - Intergovernmental Panel on Climate Change, Al Gore 2006 - Muhammad Yunus, Grameen Bank 2005 - International Atomic Energy Agency, Mohamed ElBaradei 2004 - Wangari Maathai 2003 - Shirin Ebadi 2002 - Jimmy Carter 2001 - United Nations, Kofi Annan 2000 - Kim Dae-jung 1999 - Médecins Sans Frontières 1998 - John Hume, David Trimble 1997 - International Campaign to Ban Landmines, Jody Williams 1996 - Carlos Filipe Ximenes Belo, José Ramos-Horta 1995 - Joseph Rotblat, Pugwash Conferences on Science and World Affairs 1994 - Yasser Arafat, Shimon Peres, Yitzhak Rabin 1993 - Nelson Mandela, F.W. de Klerk 1992 - Rigoberta Menchú Tum 1991 - Aung San Suu Kyi 1990 - Mikhail Gorbachev 1989 - The 14th Dalai Lama 1988 - United Nations Peacekeeping Forces 1987 - Oscar Arias Sánchez 1986 - Elie Wiesel 1985 - International Physicians for the Prevention of Nuclear War 1984 - Desmond Tutu 1983 - Lech Walesa 1982 - Alva Myrdal, Alfonso García Robles 1981 - Office of the United Nations High Commissioner for Refugees 1980 - Adolfo Pérez Esquivel 1979 - Mother Teresa 1978 - Anwar al-Sadat, Menachem Begin 1977 - Amnesty International 1976 - Betty Williams, Mairead Corrigan 1975 - Andrei Sakharov 1974 - Seán MacBride, Eisaku Sato 1973 - Henry Kissinger, Le Duc Tho 1972 - The prize money for 1972 was allocated to the Main Fund 1971 - Willy Brandt 1970 - Norman Borlaug 1969 - International Labour Organization 1968 - René Cassin 1967 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1966 - The prize money was allocated to the Special Fund of this prize section 1965 - United Nations Children's Fund 1964 - Martin Luther King Jr. 1963 - International Committee of the Red Cross, League of Red Cross Societies 1962 - Linus Pauling 1961 - Dag Hammarskjöld 1960 - Albert Lutuli 1959 - Philip Noel-Baker 1958 - Georges Pire 1957 - Lester Bowles Pearson 1956 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1955 - The prize money was allocated to the Special Fund of this prize section 1954 - Office of the United Nations High Commissioner for Refugees 1953 - George C. Marshall 1952 - Albert Schweitzer 1951 - Léon Jouhaux 1950 - Ralph Bunche 1949 - Lord Boyd Orr 1948 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1947 - Friends Service Council, American Friends Service Committee 1946 - Emily Greene Balch, John R. Mott 1945 - Cordell Hull 1944 - International Committee of the Red Cross 1943 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1942 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1941 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1940 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1939 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1938 - Nansen International Office for Refugees 1937 - Robert Cecil 1936 - Carlos Saavedra Lamas 1935 - Carl von Ossietzky 1934 - Arthur Henderson 1933 - Sir Norman Angell 1932 - The prize money was allocated to the Special Fund of this prize section 1931 - Jane Addams, Nicholas Murray Butler 1930 - Nathan Söderblom 1929 - Frank B. Kellogg 1928 - The prize money was allocated to the Special Fund of this prize section 1927 - Ferdinand Buisson, Ludwig Quidde 1926 - Aristide Briand, Gustav Stresemann 1925 - Sir Austen Chamberlain, Charles G. Dawes 1924 - The prize money was allocated to the Special Fund of this prize section 1923 - The prize money was allocated to the Special Fund of this prize section 1922 - Fridtjof Nansen 1921 - Hjalmar Branting, Christian Lange 1920 - Léon Bourgeois 1919 - Woodrow Wilson 1918 - The prize money was allocated to the Special Fund of this prize section 1917 - International Committee of the Red Cross 1916 - The prize money was allocated to the Special Fund of this prize section 1915 - The prize money was allocated to the Special Fund of this prize section 1914 - The prize money was allocated to the Special Fund of this prize section 1913 - Henri La Fontaine 1912 - Elihu Root 1911 - Tobias Asser, Alfred Fried 1910 - Permanent International Peace Bureau 1909 - Auguste Beernaert, Paul Henri d'Estournelles de Constant 1908 - Klas Pontus Arnoldson, Fredrik Bajer 1907 - Ernesto Teodoro Moneta, Louis Renault 1906 - Theodore Roosevelt 1905 - Bertha von Suttner 1904 - Institute of International Law 1903 - Randal Cremer 1902 - Élie Ducommun, Albert Gobat 1901 - Henry Dunant, Frédéric Passy

All Nobel Laureates in Medicine

The Nobel Prize in Physiology or Medicine has been awarded to 192 persons since 1901. Choose a name and click on it to go to the Laureate's page.

Jump down to: | 1980 | 1960 | 1940 | 1920 | 1901 | 2008 - Harald zur Hausen, Françoise Barré-Sinoussi, Luc Montagnier 2007 - Mario R. Capecchi, Sir Martin J. Evans, Oliver Smithies 2006 - Andrew Z. Fire, Craig C. Mello 2005 - Barry J. Marshall, J. Robin Warren 2004 - Richard Axel, Linda B. Buck 2003 - Paul C. Lauterbur, Sir Peter Mansfield 2002 - Sydney Brenner, H. Robert Horvitz, John E. Sulston 2001 - Leland H. Hartwell, Tim Hunt, Sir Paul Nurse 2000 - Arvid Carlsson, Paul Greengard, Eric R. Kandel 1999 - Günter Blobel 1998 - Robert F. Furchgott, Louis J. Ignarro, Ferid Murad 1997 - Stanley B. Prusiner 1996 - Peter C. Doherty, Rolf M. Zinkernagel 1995 - Edward B. Lewis, Christiane Nüsslein-Volhard, Eric F. Wieschaus 1994 - Alfred G. Gilman, Martin Rodbell 1993 - Richard J. Roberts, Phillip A. Sharp 1992 - Edmond H. Fischer, Edwin G. Krebs 1991 - Erwin Neher, Bert Sakmann 1990 - Joseph E. Murray, E. Donnall Thomas 1989 - J. Michael Bishop, Harold E. Varmus 1988 - Sir James W. Black, Gertrude B. Elion, George H. Hitchings 1987 - Susumu Tonegawa 1986 - Stanley Cohen, Rita Levi-Montalcini 1985 - Michael S. Brown, Joseph L. Goldstein 1984 - Niels K. Jerne, Georges J.F. Köhler, César Milstein 1983 - Barbara McClintock 1982 - Sune K. Bergström, Bengt I. Samuelsson, John R. Vane 1981 - Roger W. Sperry, David H. Hubel, Torsten N. Wiesel 1980 - Baruj Benacerraf, Jean Dausset, George D. Snell 1979 - Allan M. Cormack, Godfrey N. Hounsfield 1978 - Werner Arber, Daniel Nathans, Hamilton O. Smith 1977 - Roger Guillemin, Andrew V. Schally, Rosalyn Yalow 1976 - Baruch S. Blumberg, D. Carleton Gajdusek 1975 - David Baltimore, Renato Dulbecco, Howard M. Temin 1974 - Albert Claude, Christian de Duve, George E. Palade 1973 - Karl von Frisch, Konrad Lorenz, Nikolaas Tinbergen 1972 - Gerald M. Edelman, Rodney R. Porter 1971 - Earl W. Sutherland, Jr. 1970 - Sir Bernard Katz, Ulf von Euler, Julius Axelrod 1969 - Max Delbrück, Alfred D. Hershey, Salvador E. Luria 1968 - Robert W. Holley, H. Gobind Khorana, Marshall W. Nirenberg 1967 - Ragnar Granit, Haldan K. Hartline, George Wald 1966 - Peyton Rous, Charles B. Huggins 1965 - François Jacob, André Lwoff, Jacques Monod 1964 - Konrad Bloch, Feodor Lynen 1963 - Sir John Eccles, Alan L. Hodgkin, Andrew F. Huxley 1962 - Francis Crick, James Watson, Maurice Wilkins 1961 - Georg von Békésy 1960 - Sir Frank Macfarlane Burnet, Peter Medawar 1959 - Severo Ochoa, Arthur Kornberg 1958 - George Beadle, Edward Tatum, Joshua Lederberg 1957 - Daniel Bovet 1956 - André F. Cournand, Werner Forssmann, Dickinson W. Richards 1955 - Hugo Theorell 1954 - John F. Enders, Thomas H. Weller, Frederick C. Robbins 1953 - Hans Krebs, Fritz Lipmann 1952 - Selman A. Waksman 1951 - Max Theiler 1950 - Edward C. Kendall, Tadeus Reichstein, Philip S. Hench 1949 - Walter Hess, Egas Moniz 1948 - Paul Müller 1947 - Carl Cori, Gerty Cori, Bernardo Houssay 1946 - Hermann J. Muller 1945 - Sir Alexander Fleming, Ernst B. Chain, Sir Howard Florey 1944 - Joseph Erlanger, Herbert S. Gasser 1943 - Henrik Dam, Edward A. Doisy 1942 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1941 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1940 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1939 - Gerhard Domagk 1938 - Corneille Heymans 1937 - Albert Szent-Györgyi 1936 - Sir Henry Dale, Otto Loewi 1935 - Hans Spemann 1934 - George H. Whipple, George R. Minot, William P. Murphy 1933 - Thomas H. Morgan 1932 - Sir Charles Sherrington, Edgar Adrian 1931 - Otto Warburg 1930 - Karl Landsteiner 1929 - Christiaan Eijkman, Sir Frederick Hopkins 1928 - Charles Nicolle 1927 - Julius Wagner-Jauregg 1926 - Johannes Fibiger 1925 - The prize money was allocated to the Special Fund of this prize section 1924 - Willem Einthoven 1923 - Frederick G. Banting, John Macleod 1922 - Archibald V. Hill, Otto Meyerhof 1921 - The prize money was allocated to the Special Fund of this prize section 1920 - August Krogh 1919 - Jules Bordet 1918 - The prize money was allocated to the Special Fund of this prize section 1917 - The prize money was allocated to the Special Fund of this prize section 1916 - The prize money was allocated to the Special Fund of this prize section 1915 - The prize money was allocated to the Special Fund of this prize section 1914 - Robert Bárány 1913 - Charles Richet 1912 - Alexis Carrel 1911 - Allvar Gullstrand 1910 - Albrecht Kossel 1909 - Theodor Kocher 1908 - Ilya Mechnikov, Paul Ehrlich 1907 - Alphonse Laveran 1906 - Camillo Golgi, Santiago Ramón y Cajal 1905 - Robert Koch 1904 - Ivan Pavlov 1903 - Niels Ryberg Finsen 1902 - Ronald Ross 1901 - Emil von Behring

All Nobel Laureates in Physics The Nobel Prize in Physics has been awarded to 183 individuals since 1901. (John Bardeen was awarded the prize in both 1956 and 1972.) Click on a name to go to the Laureate's page.

Jump down to: | 1980 | 1960 | 1940 | 1920 | 1901 | 2008 - Yoichiro Nambu, Makoto Kobayashi, Toshihide Maskawa 2007 - Albert Fert, Peter Grünberg 2006 - John C. Mather, George F. Smoot 2005 - Roy J. Glauber, John L. Hall, Theodor W. Hänsch 2004 - David J. Gross, H. David Politzer, Frank Wilczek 2003 - Alexei A. Abrikosov, Vitaly L. Ginzburg, Anthony J. Leggett 2002 - Raymond Davis Jr., Masatoshi Koshiba, Riccardo Giacconi 2001 - Eric A. Cornell, Wolfgang Ketterle, Carl E. Wieman 2000 - Zhores I. Alferov, Herbert Kroemer, Jack S. Kilby 1999 - Gerardus 't Hooft, Martinus J.G. Veltman 1998 - Robert B. Laughlin, Horst L. Störmer, Daniel C. Tsui 1997 - Steven Chu, Claude Cohen-Tannoudji, William D. Phillips 1996 - David M. Lee, Douglas D. Osheroff, Robert C. Richardson 1995 - Martin L. Perl, Frederick Reines 1994 - Bertram N. Brockhouse, Clifford G. Shull 1993 - Russell A. Hulse, Joseph H. Taylor Jr. 1992 - Georges Charpak 1991 - Pierre-Gilles de Gennes 1990 - Jerome I. Friedman, Henry W. Kendall, Richard E. Taylor 1989 - Norman F. Ramsey, Hans G. Dehmelt, Wolfgang Paul 1988 - Leon M. Lederman, Melvin Schwartz, Jack Steinberger 1987 - J. Georg Bednorz, K. Alex Müller 1986 - Ernst Ruska, Gerd Binnig, Heinrich Rohrer 1985 - Klaus von Klitzing 1984 - Carlo Rubbia, Simon van der Meer 1983 - Subramanyan Chandrasekhar, William A. Fowler 1982 - Kenneth G. Wilson 1981 - Nicolaas Bloembergen, Arthur L. Schawlow, Kai M. Siegbahn 1980 - James Cronin, Val Fitch 1979 - Sheldon Glashow, Abdus Salam, Steven Weinberg 1978 - Pyotr Kapitsa, Arno Penzias, Robert Woodrow Wilson 1977 - Philip W. Anderson, Sir Nevill F. Mott, John H. van Vleck 1976 - Burton Richter, Samuel C.C. Ting 1975 - Aage N. Bohr, Ben R. Mottelson, James Rainwater 1974 - Martin Ryle, Antony Hewish 1973 - Leo Esaki, Ivar Giaever, Brian D. Josephson 1972 - John Bardeen, Leon N. Cooper, Robert Schrieffer 1971 - Dennis Gabor 1970 - Hannes Alfvén, Louis Néel 1969 - Murray Gell-Mann 1968 - Luis Alvarez 1967 - Hans Bethe 1966 - Alfred Kastler 1965 - Sin-Itiro Tomonaga, Julian Schwinger, Richard P. Feynman 1964 - Charles H. Townes, Nicolay G. Basov, Aleksandr M. Prokhorov 1963 - Eugene Wigner, Maria Goeppert-Mayer, J. Hans D. Jensen 1962 - Lev Landau 1961 - Robert Hofstadter, Rudolf Mössbauer 1960 - Donald A. Glaser 1959 - Emilio Segrè, Owen Chamberlain 1958 - Pavel A. Cherenkov, Il´ja M. Frank, Igor Y. Tamm 1957 - Chen Ning Yang, Tsung-Dao Lee 1956 - William B. Shockley, John Bardeen, Walter H. Brattain 1955 - Willis E. Lamb, Polykarp Kusch 1954 - Max Born, Walther Bothe 1953 - Frits Zernike 1952 - Felix Bloch, E. M. Purcell 1951 - John Cockcroft, Ernest T.S. Walton 1950 - Cecil Powell 1949 - Hideki Yukawa 1948 - Patrick M.S. Blackett 1947 - Edward V. Appleton 1946 - Percy W. Bridgman 1945 - Wolfgang Pauli 1944 - Isidor Isaac Rabi 1943 - Otto Stern 1942 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1941 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1940 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1939 - Ernest Lawrence 1938 - Enrico Fermi 1937 - Clinton Davisson, George Paget Thomson 1936 - Victor F. Hess, Carl D. Anderson 1935 - James Chadwick 1934 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1933 - Erwin Schrödinger, Paul A.M. Dirac 1932 - Werner Heisenberg 1931 - The prize money was allocated to the Special Fund of this prize section 1930 - Sir Venkata Raman 1929 - Louis de Broglie 1928 - Owen Willans Richardson 1927 - Arthur H. Compton, C.T.R. Wilson 1926 - Jean Baptiste Perrin 1925 - James Franck, Gustav Hertz 1924 - Manne Siegbahn 1923 - Robert A. Millikan 1922 - Niels Bohr 1921 - Albert Einstein 1920 - Charles Edouard Guillaume 1919 - Johannes Stark 1918 - Max Planck 1917 - Charles Glover Barkla 1916 - The prize money was allocated to the Special Fund of this prize section 1915 - William Bragg, Lawrence Bragg 1914 - Max von Laue 1913 - Heike Kamerlingh Onnes 1912 - Gustaf Dalén 1911 - Wilhelm Wien 1910 - Johannes Diderik van der Waals 1909 - Guglielmo Marconi, Ferdinand Braun 1908 - Gabriel Lippmann 1907 - Albert A. Michelson 1906 - J.J. Thomson 1905 - Philipp Lenard 1904 - Lord Rayleigh 1903 - Henri Becquerel, Pierre Curie, Marie Curie 1902 - Hendrik A. Lorentz, Pieter Zeeman 1901 - Wilhelm Conrad Röntgen

All Nobel Laureates in Chemistry

The Nobel Prize in Chemistry has been awarded to 153 individuals since 1901. (Frederick Sanger was awarded the prize in both 1958 and 1980.) Click on a name to go to the Laureate's page.

Jump down to: | 1980 | 1960 | 1940 | 1920 | 1901 | 2008 - Osamu Shimomura, Martin Chalfie, Roger Y. Tsien 2007 - Gerhard Ertl 2006 - Roger D. Kornberg 2005 - Yves Chauvin, Robert H. Grubbs, Richard R. Schrock 2004 - Aaron Ciechanover, Avram Hershko, Irwin Rose 2003 - Peter Agre, Roderick MacKinnon 2002 - John B. Fenn, Koichi Tanaka, Kurt Wüthrich 2001 - William S. Knowles, Ryoji Noyori, K. Barry Sharpless 2000 - Alan Heeger, Alan G. MacDiarmid, Hideki Shirakawa 1999 - Ahmed Zewail 1998 - Walter Kohn, John Pople 1997 - Paul D. Boyer, John E. Walker, Jens C. Skou 1996 - Robert F. Curl Jr., Sir Harold Kroto, Richard E. Smalley 1995 - Paul J. Crutzen, Mario J. Molina, F. Sherwood Rowland 1994 - George A. Olah 1993 - Kary B. Mullis, Michael Smith 1992 - Rudolph A. Marcus 1991 - Richard R. Ernst 1990 - Elias James Corey 1989 - Sidney Altman, Thomas R. Cech 1988 - Johann Deisenhofer, Robert Huber, Hartmut Michel 1987 - Donald J. Cram, Jean-Marie Lehn, Charles J. Pedersen 1986 - Dudley R. Herschbach, Yuan T. Lee, John C. Polanyi 1985 - Herbert A. Hauptman, Jerome Karle 1984 - Bruce Merrifield 1983 - Henry Taube 1982 - Aaron Klug 1981 - Kenichi Fukui, Roald Hoffmann 1980 - Paul Berg, Walter Gilbert, Frederick Sanger 1979 - Herbert C. Brown, Georg Wittig 1978 - Peter Mitchell 1977 - Ilya Prigogine 1976 - William Lipscomb 1975 - John Cornforth, Vladimir Prelog 1974 - Paul J. Flory 1973 - Ernst Otto Fischer, Geoffrey Wilkinson 1972 - Christian Anfinsen, Stanford Moore, William H. Stein 1971 - Gerhard Herzberg 1970 - Luis Leloir 1969 - Derek Barton, Odd Hassel 1968 - Lars Onsager 1967 - Manfred Eigen, Ronald G.W. Norrish, George Porter 1966 - Robert S. Mulliken 1965 - Robert B. Woodward 1964 - Dorothy Crowfoot Hodgkin 1963 - Karl Ziegler, Giulio Natta 1962 - Max F. Perutz, John C. Kendrew 1961 - Melvin Calvin 1960 - Willard F. Libby 1959 - Jaroslav Heyrovsky 1958 - Frederick Sanger 1957 - Lord Todd 1956 - Sir Cyril Hinshelwood, Nikolay Semenov 1955 - Vincent du Vigneaud 1954 - Linus Pauling 1953 - Hermann Staudinger 1952 - Archer J.P. Martin, Richard L.M. Synge 1951 - Edwin M. McMillan, Glenn T. Seaborg 1950 - Otto Diels, Kurt Alder 1949 - William F. Giauque 1948 - Arne Tiselius 1947 - Sir Robert Robinson 1946 - James B. Sumner, John H. Northrop, Wendell M. Stanley 1945 - Artturi Virtanen 1944 - Otto Hahn 1943 - George de Hevesy 1942 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1941 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1940 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1939 - Adolf Butenandt, Leopold Ruzicka 1938 - Richard Kuhn 1937 - Norman Haworth, Paul Karrer 1936 - Peter Debye 1935 - Frédéric Joliot, Irène Joliot-Curie 1934 - Harold C. Urey 1933 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1932 - Irving Langmuir 1931 - Carl Bosch, Friedrich Bergius 1930 - Hans Fischer 1929 - Arthur Harden, Hans von Euler-Chelpin 1928 - Adolf Windaus 1927 - Heinrich Wieland 1926 - The Svedberg 1925 - Richard Zsigmondy 1924 - The prize money was allocated to the Special Fund of this prize section 1923 - Fritz Pregl 1922 - Francis W. Aston 1921 - Frederick Soddy 1920 - Walther Nernst 1919 - The prize money was allocated to the Special Fund of this prize section 1918 - Fritz Haber 1917 - The prize money was allocated to the Special Fund of this prize section 1916 - The prize money was allocated to the Special Fund of this prize section 1915 - Richard Willstätter 1914 - Theodore W. Richards 1913 - Alfred Werner 1912 - Victor Grignard, Paul Sabatier 1911 - Marie Curie 1910 - Otto Wallach 1909 - Wilhelm Ostwald 1908 - Ernest Rutherford 1907 - Eduard Buchner 1906 - Henri Moissan 1905 - Adolf von Baeyer 1904 - Sir William Ramsay 1903 - Svante Arrhenius 1902 - Emil Fischer 1901 - Jacobus H. van 't Hoff

All Nobel Laureates in Literature

The Nobel Prize in Literature has been awarded to 105 persons since 1901. Choose a name and click on it to go to the Laureate's page.

Jump down to: | 1980 | 1960 | 1940 | 1920 | 1901 | 2008 - Jean-Marie Gustave Le Clézio 2007 - Doris Lessing 2006 - Orhan Pamuk 2005 - Harold Pinter 2004 - Elfriede Jelinek 2003 - J. M. Coetzee 2002 - Imre Kertész 2001 - V. S. Naipaul 2000 - Gao Xingjian 1999 - Günter Grass 1998 - José Saramago 1997 - Dario Fo 1996 - Wislawa Szymborska 1995 - Seamus Heaney 1994 - Kenzaburo Oe 1993 - Toni Morrison 1992 - Derek Walcott 1991 - Nadine Gordimer 1990 - Octavio Paz 1989 - Camilo José Cela 1988 - Naguib Mahfouz 1987 - Joseph Brodsky 1986 - Wole Soyinka 1985 - Claude Simon 1984 - Jaroslav Seifert 1983 - William Golding 1982 - Gabriel García Márquez 1981 - Elias Canetti 1980 - Czeslaw Milosz 1979 - Odysseus Elytis 1978 - Isaac Bashevis Singer 1977 - Vicente Aleixandre 1976 - Saul Bellow 1975 - Eugenio Montale 1974 - Eyvind Johnson, Harry Martinson 1973 - Patrick White 1972 - Heinrich Böll 1971 - Pablo Neruda 1970 - Alexandr Solzhenitsyn 1969 - Samuel Beckett 1968 - Yasunari Kawabata 1967 - Miguel Angel Asturias 1966 - Shmuel Agnon, Nelly Sachs 1965 - Mikhail Sholokhov 1964 - Jean-Paul Sartre 1963 - Giorgos Seferis 1962 - John Steinbeck 1961 - Ivo Andric 1960 - Saint-John Perse 1959 - Salvatore Quasimodo 1958 - Boris Pasternak 1957 - Albert Camus 1956 - Juan Ramón Jiménez 1955 - Halldór Laxness 1954 - Ernest Hemingway 1953 - Winston Churchill 1952 - François Mauriac 1951 - Pär Lagerkvist 1950 - Bertrand Russell 1949 - William Faulkner 1948 - T.S. Eliot 1947 - André Gide 1946 - Hermann Hesse 1945 - Gabriela Mistral 1944 - Johannes V. Jensen 1943 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1942 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1941 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1940 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1939 - Frans Eemil Sillanpää 1938 - Pearl Buck 1937 - Roger Martin du Gard 1936 - Eugene O'Neill 1935 - The prize money was with 1/3 allocated to the Main Fund and with 2/3 to the Special Fund of this prize section 1934 - Luigi Pirandello 1933 - Ivan Bunin 1932 - John Galsworthy 1931 - Erik Axel Karlfeldt 1930 - Sinclair Lewis 1929 - Thomas Mann 1928 - Sigrid Undset 1927 - Henri Bergson 1926 - Grazia Deledda 1925 - George Bernard Shaw 1924 - Wladyslaw Reymont 1923 - William Butler Yeats 1922 - Jacinto Benavente 1921 - Anatole France 1920 - Knut Hamsun 1919 - Carl Spitteler 1918 - The prize money was allocated to the Special Fund of this prize section 1917 - Karl Gjellerup, Henrik Pontoppidan 1916 - Verner von Heidenstam 1915 - Romain Rolland 1914 - The prize money was allocated to the Special Fund of this prize section 1913 - Rabindranath Tagore 1912 - Gerhart Hauptmann 1911 - Maurice Maeterlinck 1910 - Paul Heyse 1909 - Selma Lagerlöf 1908 - Rudolf Eucken 1907 - Rudyard Kipling 1906 - Giosuè Carducci 1905 - Henryk Sienkiewicz 1904 - Frédéric Mistral, José Echegaray 1903 - Bjørnstjerne Bjørnson 1902 - Theodor Mommsen 1901 - Sully Prudhomme

All Laureates in Economics

The Sveriges Riksbank Prize in Economic Sciences in Memory of Alfred Nobel has been awarded to 61 individuals since 1969. Choose a name and click on it to go to the Laureate's page.

Jump down to: | 1980 | 1969 | 2007 - Leonid Hurwicz, Eric S. Maskin, Roger B. Myerson 2006 - Edmund S. Phelps 2005 - Robert J. Aumann, Thomas C. Schelling 2004 - Finn E. Kydland, Edward C. Prescott 2003 - Robert F. Engle III, Clive W.J. Granger 2002 - Daniel Kahneman, Vernon L. Smith 2001 - George A. Akerlof, A. Michael Spence, Joseph E. Stiglitz 2000 - James J. Heckman, Daniel L. McFadden 1999 - Robert A. Mundell 1998 - Amartya Sen 1997 - Robert C. Merton, Myron S. Scholes 1996 - James A. Mirrlees, William Vickrey 1995 - Robert E. Lucas Jr. 1994 - John C. Harsanyi, John F. Nash Jr., Reinhard Selten 1993 - Robert W. Fogel, Douglass C. North 1992 - Gary S. Becker 1991 - Ronald H. Coase 1990 - Harry M. Markowitz, Merton H. Miller, William F. Sharpe 1989 - Trygve Haavelmo 1988 - Maurice Allais 1987 - Robert M. Solow 1986 - James M. Buchanan Jr. 1985 - Franco Modigliani 1984 - Richard Stone 1983 - Gerard Debreu 1982 - George J. Stigler 1981 - James Tobin 1980 - Lawrence R. Klein 1979 - Theodore W. Schultz, Sir Arthur Lewis 1978 - Herbert A. Simon 1977 - Bertil Ohlin, James E. Meade 1976 - Milton Friedman 1975 - Leonid Vitaliyevich Kantorovich, Tjalling C. Koopmans 1974 - Gunnar Myrdal, Friedrich August von Hayek 1973 - Wassily Leontief 1972 - John R. Hicks, Kenneth J. Arrow 1971 - Simon Kuznets 1970 - Paul A. Samuelson 1969 - Ragnar Frisch, Jan Tinbergen

HIGH PERFORMANCE LIQUID CHROMATOGRAPHY - HPLCHigh performance liquid chromatography is a powerful tool in analysis. This page looks at how it is carried out and shows how it uses the same principles as in thin layer chromatography and column chromatography. Carrying out HPLCIntroductionHigh performance liquid chromatography is basically a highly improved form of column chromatography. Instead of a solvent being allowed to drip through a column under gravity, it is forced through under high pressures of up to 400 atmospheres. That makes it much faster.It also allows you to use a very much smaller particle size for the column packing material which gives a much greater surface area for interactions between the stationary phase and the molecules flowing past it. This allows a much better separation of the components of the mixture.The other major improvement over column chromatography concerns the detection methods which can be used. These methods are highly automated and extremely sensitive.The column and the solventConfusingly, there are two variants in use in HPLC depending on the relative polarity of the solvent and the stationary phase.Normal phase HPLCThis is essentially just the same as you will already have read about in thin layer chromatography or column chromatography. Although it is described as "normal", it isn't the most commonly used form of HPLC.The column is filled with tiny silica particles, and the solvent is non-polar - hexane, for example. A typical column has an internal diameter of 4.6 mm (and may be less than that), and a length of 150 to 250 mm.Polar compounds in the mixture being passed through the column will stick longer to the polar silica than non-polar compounds will. The non-polar ones will therefore pass more quickly through the column.Reversed phase HPLCIn this case, the column size is the same, but the silica is modified to make it non-polar by attaching long hydrocarbon chains to its surface - typically with either 8 or 18 carbon atoms in them. A polar solvent is used - for example, a mixture of water and an alcohol such as methanol.In this case, there will be a strong attraction between the polar solvent and polar molecules in the mixture being passed through the column. There won't be as much attraction between the hydrocarbon chains attached to the silica (the stationary phase) and the polar molecules in the solution. Polar molecules in the mixture will therefore spend most of their time moving with the solvent.Non-polar compounds in the mixture will tend to form attractions with the hydrocarbon groups because of van der Waals dispersion forces. They will also be less soluble in the solvent because of the need to break hydrogen bonds as they squeeze in between the water or methanol molecules, for example. They therefore spend less time in solution in the solvent and this will slow them down on their way through the column.That means that now it is the polar molecules that will travel through the column more quickly.Reversed phase HPLC is the most commonly used form of HPLC. Note: I have been a bit careful about how I have described the attractions of the non-polar molecules to the surface of the stationary phase. In particular, I have avoided the use of the word "adsorpion". Adsorption is when a molecule sticks to the surface of a solid. Especially if you had small molecules in your mixture, some could get in between the long C18 chains to give what is essentially a solution. You could therefore say that non-polar molecules were more soluble in the hydrocarbon on the surface of the silica than they are in the polar solvent - and so spend more time in this alternative "solvent". Where a solute divides itself between two different solvents because it is more soluble in one than the other, we call it partition.So is this adsorption or partition? You could argue it both ways! Be prepared to find it described as either. Looking at the whole processA flow scheme for HPLC Injection of the sampleInjection of the sample is entirely automated, and you wouldn't be expected to know how this is done at this introductory level. Because of the pressures involved, it is not the same as in gas chromatography (if you have already studied that).Retention timeThe time taken for a particular compound to travel through the column to the detector is known as its retention time. This time is measured from the time at which the sample is injected to the point at which the display shows a maximum peak height for that compound.Different compounds have different retention times. For a particular compound, the retention time will vary depending on:·	the pressure used (because that affects the flow rate of the solvent)·	the nature of the stationary phase (not only what material it is made of, but also particle size)·	the exact composition of the solvent·	the temperature of the columnThat means that conditions have to be carefully controlled if you are using retention times as a way of identifying compounds.The detectorThere are several ways of detecting when a substance has passed through the column. A common method which is easy to explain uses ultra-violet absorption.Many organic compounds absorb UV light of various wavelengths. If you have a beam of UV light shining through the stream of liquid coming out of the column, and a UV detector on the opposite side of the stream, you can get a direct reading of how much of the light is absorbed.The amount of light absorbed will depend on the amount of a particular compound that is passing through the beam at the time. You might wonder why the solvents used don't absorb UV light. They do! But different compounds absorb most strongly in different parts of the UV spectrum.Methanol, for example, absorbs at wavelengths below 205 nm, and water below 190 nm. If you were using a methanol-water mixture as the solvent, you would therefore have to use a wavelength greater than 205 nm to avoid false readings from the solvent. Interpreting the output from the detectorThe output will be recorded as a series of peaks - each one representing a compound in the mixture passing through the detector and absorbing UV light. As long as you were careful to control the conditions on the column, you could use the retention times to help to identify the compounds present - provided, of course, that you (or somebody else) had already measured them for pure samples of the various compounds under those identical conditions.But you can also use the peaks as a way of measuring the quantities of the compounds present. Let's suppose that you are interested in a particular compound, X.If you injected a solution containing a known amount of pure X into the machine, not only could you record its retention time, but you could also relate the amount of X to the peak that was formed.The area under the peak is proportional to the amount of X which has passed the detector, and this area can be calculated automatically by the computer linked to the display. The area it would measure is shown in green in the (very simplified) diagram. If the solution of X was less concentrated, the area under the peak would be less - although the retention time will still be the same. For example: This means that it is possible to calibrate the machine so that it can be used to find how much of a substance is present - even in very small quantities.Be careful, though! If you had two different substances in the mixture (X and Y) could you say anything about their relative amounts? Not if you were using UV absorption as your detection method. In the diagram, the area under the peak for Y is less than that for X. That may be because there is less Y than X, but it could equally well be because Y absorbs UV light at the wavelength you are using less than X does. There might be large quantities of Y present, but if it only absorbed weakly, it would only give a small peak. Note: If you want lots more detail about HPLC you could explore the site operated by Waters Corporation - a supplier of HPLC equipment. Linking to other sites is always a little bit hazardous because sites change. If you find that this link doesn't work, please contact me via the address on the About this site page. Coupling HPLC to a mass spectrometerThis is where it gets really clever! When the detector is showing a peak, some of what is passing through the detector at that time can be diverted to a mass spectrometer. There it will give a fragmentation pattern which can be compared against a computer database of known patterns. That means that the identity of a huge range of compounds can be found without having to know their retention times. Gas-liquid chromatography Gas-liquid chromatography (GLC), or simply gas chromatography (GC), is a type of chromatography in which the mobile phase is a carrier gas, usually an inert gas such as helium or an unreactive gas such as nitrogen, and the stationary phase is a microscopic layer of liquid or polymer on an inert solid support, inside glass or metal tubing, called a column. The instrument used to perform gas chromatographic separations is called a gas chromatograph (also: aerograph, gas separator). Gas Chromatography is different from other forms of chromatography (HPLC, TLC, etc.) because the solutions travel through the column in a gas state. The interactions of these gaseous analytes with the walls of the column (coated by different stationary phases) causes different compounds to elute at different times called retention time. The comparison of these retention times is the analytical power of GC. This makes it very similar to HPLC. History Chromatography dates to 1903 in the work of the Russian scientist, Mikhail Semenovich Tswett. German graduate student Fritz Prior developed solid state gas chromatography in 1947. Archer John Porter Martin, who was awarded the Nobel Prize for his work in developing liquid-liquid (1941) and paper (1944) chromatography, laid the foundation for the development of gas chromatography and later produced liquid-gas chromatography (1950). GC analysis A gas chromatograph is a chemical analysis instrument for separating chemicals in a complex sample. A gas chromatograph uses a flow-through narrow tube known as the column, through which different chemical constituents of a sample pass in a gas stream (carrier gas, mobile phase) at different rates depending on their various chemical and physical properties and their interaction with a specific column filling, called the stationary phase. As the chemicals exit the end of the column, they are detected and identified electronically. The function of the stationary phase in the column is to separate different components, causing each one to exit the column at a different time (retention time). Other parameters that can be used to alter the order or time of retention are the carrier gas flow rate, and the temperature. In a GC analysis, a known volume of gaseous or liquid analyte is injected into the "entrance" (head) of the column, usually using a microsyringe (or, solid phase microextraction fibers, or a gas source switching system). As the carrier gas sweeps the analyte molecules through the column, this motion is inhibited by the adsorption of the analyte molecules either onto the column walls or onto packing materials in the column. The rate at which the molecules progress along the column depends on the strength of adsorption, which in turn depends on the type of molecule and on the stationary phase materials. Since each type of molecule has a different rate of progression, the various components of the analyte mixture are separated as they progress along the column and reach the end of the column at different times (retention time). A detector is used to monitor the outlet stream from the column; thus, the time at which each component reaches the outlet and the amount of that component can be determined. Generally, substances are identified (qualitatively) by the order in which they emerge (elute) from the column and by the retention time of the analyte in the column. Physical components [edit] Autosamplers The autosampler provides the means to introduce automatically a sample into the inlets. Manual insertion of the sample is possible but is no longer common. Automatic insertion provides better reproducibility and time-optimization. Different kinds of autosamplers exist. Autosamplers can be classified in relation to sample capacity (auto-injectors VS autosamplers, where auto-injectors can work a small number of samples), to robotic technologies (XYZ robot VS rotating/SCARA-robot – the most common), or to analysis: ·	Liquid ·	Static head-space by syringe technology ·	Dynamic head-space by transfer-line technology ·	SPME Traditionally autosampler manufactures are different from GC manufactures and currently no GC manufacture offers a complete range of autosamplers. Historically, the countries most active in autosampler technology development are the United States, Italy, and Switzerland.

Inlets The column inlet (or injector) provides the means to introduce a sample into a continuous flow of carrier gas. The inlet is a piece of hardware attached to the column head. Common inlet types are: ·	S/SL (Split/Splitless) injector; a sample is introduced into a heated small chamber via a syringe through a septum - the heat facilitates volatilization of the sample and sample matrix. The carrier gas then either sweeps the entirety (splitless mode) or a portion (split mode) of the sample into the column. In split mode, a part of the sample/carrier gas mixture in the injection chamber is exhausted through the split vent. ·	On-column inlet; the sample is here introduced in its entirety without heat. ·	PTV injector; Temperature-programmed sample introduction was first described by Vogt in 1979. Originally Vogt developed the technique as a method for the introduction of large sample volumes (up to 250 µL) in capillary GC. Vogt introduced the sample into the liner at a controlled injection rate. The temperature of the liner was chosen slightly below the boiling point of the solvent. The low-boiling solvent was continuously evaporated and vented through the split line. Based on this technique, Poy developed the Programmed Temperature Vaporising injector; PTV. By introducing the sample at a low initial liner temperature many of the disadvantages of the classic hot injection techniques could be circumvented. ·	Gas source inlet or gas switching valve; gaseous samples in collection bottles are connected to what is most commonly a six-port switching valve. The carrier gas flow is not interrupted while a sample can be expanded into a previously evacuated sample loop. Upon switching, the contents of the sample loop are inserted into the carrier gas stream. ·	P/T (Purge-and-Trap) system; An inert gas is bubbled through an aqueous sample causing insoluble volatile chemicals to be purged from the matrix. The volatiles are 'trapped' on an absorbent column (known as a trap or concentrator) at ambient temperature. The trap is then heated and the volatiles are directed into the carrier gas stream. Samples requiring preconcentration or purification can be introduced via such a system, usually hooked up to the S/SL port. ·	SPME (solid phase microextraction) offers a convenient, low-cost alternative to P/T systems with the versatility of a syringe and simple use of the S/SL port. Columns Two types of columns are used in GC: ·	Packed columns are 1.5 - 10 m in length and have an internal diameter of 2 - 4 mm. The tubing is usually made of stainless steel or glass and contains a packing of finely divided, inert, solid support material (eg. diatomaceous earth) that is coated with a liquid or solid stationary phase. The nature of the coating material determines what type of materials will be most strongly adsorbed. Thus numerous columns are available that are designed to separate specific types of compounds. ·	Capillary columns have a very small internal diameter, on the order of a few tenths of millimeters, and lengths between 25-60 meters are common. The inner column walls are coated with the active materials (WCOT columns), some columns are quasi solid filled with many parallel micropores (PLOT columns). Most capillary columns are made of fused-silica with a polyimide outer coating. These columns are flexible, so a very long column can be wound into a small coil. ·	New developments are sought where stationary phase incompatibilities lead to geometric solutions of parallel columns within one column. Among these new developments are: o	Internally heated microFAST columns, where two columns, an internal heating wire and a temperature sensor are combined within a common column sheath (microFAST); o	Micropacked columns (1/16" OD) are column-in-column packed columns where the outer column space has a packing different from the inner column space, thus providing the separation behaviour of two columns in one. They can be easily fit to inlets and detectors of a capillary column instrument. The temperature-dependence of molecular adsorption and of the rate of progression along the column necessitates a careful control of the column temperature to within a few tenths of a degree for precise work. Reducing the temperature produces the greatest level of separation, but can result in very long elution times. For some cases temperature is ramped either continuously or in steps to provide the desired separation. This is referred to as a temperature program. Electronic pressure control can also be used to modify flow rate during the analysis, aiding in faster run times while keeping acceptable levels of separation. The choice of carrier gas (mobile phase) is important, with hydrogen being the most efficient and providing the best separation. However, helium has a larger range of flowrates that are comparable to hydrogen in efficiency, with the added advantage that helium is non-flammable, and works with a greater number of detectors. Therefore, helium is the most common carrier gas used. Detectors A number of detectors are used in gas chromatography. The most common are the flame ionization detector (FID) and the thermal conductivity detector (TCD). Both are sensitive to a wide range of components, and both work over a wide range of concentrations. While TCDs are essentially universal and can be used to detect any component other than the carrier gas (as long as their thermal conductivities are different than that of the carrier gas, at detector temperature), FIDs are sensitive primarily to hydrocarbons, and are more sensitive to them than TCD. However, an FID cannot detect water. Both detectors are also quite robust. Since TCD is non-destructive, it can be operated in-series before an FID (destructive), thus providing complementary detection of the same analytes. Other detectors are sensitive only to specific types of substances, or work well only in narrower ranges of concentrations. They include: ·	discharge ionization detector (DID), which uses a high-voltage A DID is an ion detector which uses a high-voltage electric discharge to produce ions. The spark ionizes helium atoms that are mixed with components as they elute from the GC's column, causing the components to become ionized. The ions produce an electric current, which is the signal output of the detector. The greater the concentration of the component, the more ions are produced, and the greater the current. ·	electron capture detector (ECD), ·	                                 is a device used in gas chromatography that can detect tiny amounts of chemical compounds in a sample. The electron capture detector is used for detecting electron-absorbing components in the output stream of a gas chromatograph. The ECD uses a radioactive Beta particle (electron) emitter, typically, a metal foil holding 10 millicuries of Nickel-63. The electrons formed are attracted to a positively charged anode, generating a steady current. As the sample is carried into the detector by a stream of nitrogen or a 5% methane, 95% argon mixture, analyte molecules capture the electrons and reduce the current between the collector anode and a cathode. The analyte concentration is thus proportional to the degree of electron capture, and this detector is particularly sensitive to halogens, organometallic compounds, nitriles, or nitro compounds ·	flame photometric detector (FPD) ·	Hall electrolytic conductivity detector (ElCD) ·	helium ionization detector (HID) ·	nitrogen phosphorus detector (NPD) ·	mass selective detector (MSD) ·	photo-ionization detector (PID) ·	pulsed discharge ionization detector (PDD) ·	thermal energy analyzer (TEA) Some gas chromatographs are connected to a mass spectrometer which acts as the detector. The combination is known as GC-MS. Some GC-MS are connected to an NMR spectrometer which acts as a back up detector. This combination is known as GC-MS-NMR. Some GC-MS-NMR are connected to an infrared spectrophotometer which acts as a back up detector. This combination is known as GC-MS-NMR-IR. It must, however, be stressed this is very rare as most analyses needed can be concluded via purely GC-MS. Methods The method is the collection of conditions in which the GC operates for a given analysis. Method development is the process of determining what conditions are adequate and/or ideal for the analysis required. Conditions which can be varied to accommodate a required analysis include inlet temperature, detector temperature, column temperature and temperature program, carrier gas and carrier gas flow rates, the column's stationary phase, diameter and length, inlet type and flow rates, sample size and injection technique. Depending on the detector(s) (see below) installed on the GC, there may be a number of detector conditions that can also be varied. Some GCs also include valves which can change the route of sample and carrier flow, and the timing of the turning of these valves can be important to method development. Carrier gas selection and flow rates Typical carrier gases include helium, nitrogen, argon, hydrogen and air. Which gas to use is usually determined by the detector being used, for example, a DID requires helium as the carrier gas. When analyzing gas samples, however, the carrier is sometimes selected based on the sample's matrix, for example, when analyzing a mixture in argon, an argon carrier is preferred, because the argon in the sample does not show up on the chromatogram. Safety and availability can also influence carrier selection, for example, hydrogen is flammable, and high-purity helium can be difficult to obtain in some areas of the world. (See: Helium--occurrence and production.) The purity of the carrier gas is also frequently determined by the detector, though the level of sensitivity needed can also play a significant role. Typically, purities of 99.995% or higher are used. Trade names for typical purities include "Zero Grade," "Ultra-High Purity (UHP) Grade," "4.5 Grade" and "5.0 Grade." The carrier gas flow rate affects the analysis in the same way that temperature does (see above). The higher the flow rate the faster the analysis, but the lower the separation between analytes. Selecting the flow rate is therefore the same compromise between the level of separation and length of analysis as selecting the column temperature. With GCs made before the 1990s, carrier flow rate was controlled indirectly by controlling the carrier inlet pressure, or "column head pressure." The actual flow rate was measured at the outlet of the column or the detector with an electronic flow meter, or a bubble flow meter, and could be an involved, time consuming, and frustrating process. The pressure setting was not able to be varied during the run, and thus the flow was essentially constant during the analysis. The relation between flow rate and inlet pressure is calculated with Poiseuille's equation for compressible fluids. Many modern GCs, however, electronically measure the flow rate, and electronically control the carrier gas pressure to set the flow rate. Consequently, carrier pressures and flow rates can be adjusted during the run, creating pressure/flow programs similar to temperature programs. [edit] Inlet types and flow rates The choice of inlet type and injection technique depends on if the sample is in liquid, gas, adsorbed, or solid form, and on whether a solvent matrix is present that has to be vaporized. Dissolved samples can be introduced directly onto the column via a COC injector, if the conditions are well known; if a solvent matrix has to be vaporized and partially removed, a S/SL injector is used (most common injection technique); gaseous samples (e.g., air cylinders) are usually injected using a gas switching valve system; adsorbed samples (e.g., on adsorbent tubes) are introduced using either an external (on-line or off-line) desorption apparatus such as a purge-and-trap system, or are desorbed in the S/SL injector (SPME applications). Sample size and injection technique Sample injection The rule of ten in gas chromatography The real chromatographic analysis starts with the introduction of the sample onto the column. The development of capillary gas chromatography resulted in many practical problems with the injection technique. The technique of on-column injection, often used with packed columns, is usually not possible with capillary columns. The injection system, in the capillary gas chromatograph, should fulfil the following two requirements: 1.	The amount injected should not overload the column. 2.	The width of the injected plug should be small compared to the spreading due to the chromatographic process. Failure to comply with this requirement will reduce the separation capability of the column. As a general rule, the volume injected, Vinj, and the volume of the detector cell, Vdet, should be about 1/10 of the volume occupied by the portion of sample containing the molecules of interest (analytes) when they exit the column. Some general requirements, which a good injection technique should fulfill, are: ·	It should be possible to obtain the column’s optimum separation efficiency. ·	It should allow accurate and reproducible injections of small amounts of representative samples. ·	It should induce no change in sample composition. It should not exhibit discrimination based on differences in boiling point, polarity, concentration or thermal/catalytic stability. ·	It should be applicable for trace analysis as well as for undiluted samples. [edit] Column selection [edit] Column temperature and temperature program

A gas chromatography oven, open to show a capillary column The column(s) in a GC are contained in an oven, the temperature of which is precisely controlled electronically. (When discussing the "temperature of the column," an analyst is technically referring to the temperature of the column oven. The distinction, however, is not important and will not subsequently be made in this article.) The rate at which a sample passes through the column is directly proportional to the temperature of the column. The higher the column temperature, the faster the sample moves through the column. However, the faster a sample moves through the column, the less it interacts with the stationary phase, and the less the analytes are separated. In general, the column temperature is selected to compromise between the length of the analysis and the level of separation. A method which holds the column at the same temperature for the entire analysis is called "isothermal." Most methods, however, increase the column temperature during the analysis, the initial temperature, rate of temperature increase (the temperature "ramp") and final temperature is called the "temperature program." A temperature program allows analytes that elute early in the analysis to separate adequately, while shortening the time it takes for late-eluting analytes to pass through the column. [edit] Data reduction and analysis Qualitative analysis: Generally chromatographic data is presented as a graph of detector response (y-axis) against retention time (x-axis). This provides a spectrum of peaks for a sample representing the analytes present in a sample eluting from the column at different times. Retention time can be used to identify analytes if the method conditions are constant. Also, the pattern of peaks will be constant for a sample under constant conditions and can identify complex mixtures of analytes. In most modern applications however the GC is connected to a mass spectrometer or similar detector that is capable of identifying the analytes represented by the peaks. Quantitive analysis: The area under a peak is proportional to the amount of analyte present. By calculating the area of the peak using the mathematical function of integration, the concentration of an analyte in the original sample can be determined. Concentration can be calculated using a calibration curve created by finding the response for a series of concentrations of analyte, or by determining the relative response factor of an analyte. The relative response factor is the expected ratio of an analyte to an internal standard (or external standard) and is calculated by finding the response of a known amount of analyte and a constant amount of internal standard (a chemical added to the sample at a constant concentration, with a distinct retention time to the analyte). In most modern GC-MS systems, computer software is used to draw and integrate peaks, and match MS spectra to library spectra. [edit] Application In general, substances that vaporize below ca. 300 °C (and therefore are stable up to that temperature) can be measured quantitatively. The samples are also required to be salt-free; they should not contain ions. Very minute amounts of a substance can be measured, but it is often required that the sample must be measured in comparison to a sample containing the pure, suspected substance. Various temperature programs can be used to make the readings more meaningful; for example to differentiate between substances that behave similarly during the GC process. Professionals working with GC analyze the content of a chemical product, for example in assuring the quality of products in the chemical industry; or measuring toxic substances in soil, air or water. GC is very accurate if used properly and can measure picomoles of a substance in a 1 ml liquid sample, or parts-per-billion concentrations in gaseous samples. In practical courses at colleges, students sometimes get acquainted to the GC by studying the contents of Lavender oil or measuring the ethylene that is secreted by Nicotiana benthamiana plants after artificially injuring their leaves. These GC analyses hydrocarbons (C2-C40+). In a typical experiment, a packed column is used to separate the light gases, which are then detected with a TCD. The hydrocarbons are separated using a capillary column and detected with an FID. A complication with light gas analyses that include H2 is that He, which is the most common and most sensitive inert carrier (sensitivity is proportional to molecular mass) has an almost identical thermal conductivity to hydrogen (it is the difference in thermal conductivity between two separate filaments in a Wheatstone Bridge type arrangement that shows when a component has been eluted). For this reason, dual TCD instruments are used with a separate channel for hydrogen that uses nitrogen as a carrier are common. Argon is often used when analysing gas phase chemistry reactions such as F-T synthesis so that a single carrier gas can be used rather than 2 separate ones. The sensitivity is less but this is a tradeoff for simplicity in the gas supply.

Capillary electrophoresis Capillary electrophoresis (CE), also known as capillary zone electrophoresis (CZE), can be used to separate ionic species by their charge and frictional forces. In traditional electrophoresis, electrically charged analytes move in a conductive liquid medium under the influence of an electric field. Introduced in the 1960s, the technique of capillary electrophoresis (CE) was designed to separate species based on their size to charge ratio in the interior of a small capillary filled with an electrolyte. While its use has been sporadic, CE offers unparalleled resolution and selectivity allowing for separation of analytes with very little physical difference. Efficiencies of millions of plates are routinely reported. Once thought impossible, separation of large proteins differing in only one amino acid (ie. D-Lysine substituted for L-Lysine) and even an isotopic separation of 14N and 15N ammonium hydroxide have been reported.[1] No other technique has shown such powerful selectivity with the ability for extremely high sensitivity. As few as 6 molecules of a substance have been separated and detected with the help of laser-induced fluorescence (LIF). Instrumentation The instrumentation needed to perform capillary electrophoresis is relatively simple. A basic schematic of a capillary electrophoresis system is shown in figure 1. The system's main components are a sample vial, source and destination vials, a capillary, electrodes, a high-voltage power supply, a detector, and a data output and handling device. The source vial, destination vial and capillary are filled with an electrolyte such as an aqueous buffer solution. To introduce the sample, the capillary inlet is placed into a vial containing the sample and then returned to the source vial (sample is introduced into the capillary via capillary action, pressure, or siphoning). The migration of the analytes is then initiated by an electric field that is applied between the source and destination vials and is supplied to the electrodes by the high-voltage power supply. It is important to note that all ions, positive or negative, are pulled through the capillary in the same direction by electroosmotic flow, as will be explained. The analytes separate as they migrate due to their electrophoretic mobility, as will be explained, and are detected near the outlet end of the capillary. The output of the detector is sent to a data output and handling device such as an integrator or computer. The data is then displayed as an electropherogram, which reports detector response as a function of time. Separated chemical compounds appear as peaks with different retention times in an electropherogram.[2] Detection Separation by capillary electrophoresis can be detected by several detection devices. The majority of commercial systems use UV or UV-Vis absorbance as their primary mode of detection. In these systems, a section of the capillary itself is used as the detection cell. The use of on-tube detection enables detection of separated analytes with no loss of resolution. In general, capillaries used in capillary electrophoresis are coated with a polymer for increased stability. The portion of the capillary used for UV detection, however, must be optically transparent. Bare capillaries can break relatively easily and, as a result, capillaries with transparent coatings are available to increase the stability of the cell window. The path length of the detection cell in capillary electrophoresis (~ 50 micrometers) is far less than that of a traditional UV cell (~ 1 cm). According to the Beer-Lambert law, the sensitivity of the detector is proportional to the path length of the cell. To improve the sensitivity, the path length can be increased, though this results in a loss of resolution. The capillary tube itself can be expanded at the detection point, creating a "bubble cell" with a longer path length or additional tubing can be added at the detection point as shown in figure 2. Both of these methods, however, will decrease the resolution of the separation.[3]

Figure 2: Techniques for increasing the pathlength of the capillary: a.) a bubble cell and b.) a z-cell (additional tubing).[2] Fluorescence detection can also be used in capillary electrophoresis for samples that naturally fluoresce or are chemically modified to contain fluorescent tags. This mode of detection offers high sensitivity and improved selectivity for these samples, but cannot be utilized for samples that do not fluoresce. The set-up for fluorescence detection in a capillary electrophoresis system can be complicated. The method requires that the light beam be focused on the capillary, which can be difficult for many light sources.[3] Laser-induced fluorescence has been used in CE systems with detection limits as low as 10-18 to 10-21 mol. The sensitivity of the technique is attributed to the high intensity of the incident light and the ability to accurately focus the light on the capillary.[2] In order to obtain the identity of sample components, capillary electrophoresis can be directly coupled with mass spectrometers or Surface Enhanced Raman Spectroscopy (SERS). In most systems, the capillary outlet is introduced into an ion source that utilizes electrospray ionization (ESI). The resulting ions are then analyzed by the mass spectrometer. This set-up requires volatile buffer solutions, which will affect the range of separation modes that can be employed and the degree of resolution that can be achieved.[3] The measurement and analysis are mostly done with a specialized gel analysis software. For CE-SERS, capillary electrophoresis eluants can be deposited onto a SERS-active substrate. Analyte retention times can be translated into spatial distance by moving the SERS-active substrate at a constant rate during capillary electrophoresis. This allows the subsequent spectroscopic technique to be applied to specific eluants for identification with high sensitivity. SERS-active substrates can be chosen that do not interfere with the spectrum of the analytes.[4] [edit] Modes of separation The separation of compounds by capillary electrophoresis is dependent on the differential migration of analytes in an applied electric field. The electrophoretic migration velocity (up) of an analyte toward the electrode of opposite charge is: where μp is the electrophoretic mobility and E is the electric field strength. The electrophoretic mobility is proportional to the ionic charge of a sample and inversely proportional to any frictional forces present in the buffer. When two species in a sample have different charges or experience different frictional forces, they will separate from one another as they migrate through a buffer solution. The frictional forces experienced by an analyte ion depend on the viscosity (η) of the medium and the size and shape of the ion.[3] Accordingly, the electrophoretic mobility of an analyte at a given pH is given by: where z is the net charge of the analyte and r is the Stokes radius of the analyte. The Stokes radius is given by: where kB is the Boltzmann constant, and T is the temperature, D is the diffusion coefficient. These equations indicate that the electrophoretic mobility of the analyte is proportional to the charge of the analyte and inversely proportional to its radius. The electrophoretic mobility can be determined experimentally from the migration time and the field strength: where L is the distance from the inlet to the detection point, tr is the time required for the analyte to reach the detection point (migration time), V is the applied voltage (field strength), and Lt is the total length of the capillary.[3] Since only charged ions are affected by the electric field, neutral analytes are poorly separated by capillary electrophoresis. The velocity of migration of an analyte in capillary electrophoresis will also depend upon the rate of electroosmotic flow (EOF) of the buffer solution. In a typical system, the electroosmotic flow is directed toward the negatively charged cathode so that the buffer flows through the capillary from the source vial to the destination vial. Separated by differing electrophoretic mobilities, analytes migrate toward the electrode of opposite charge.[2] As a result, negatively charged analytes are attracted to the positively charged anode, counter to the EOF, while positively charged analytes are attracted to the cathode, in agreement with the EOF as depicted in figure 3. Figure 3: Diagram of the separation of charged and neutral analytes (A) according to their respective electrophoretic and electroosmotic flow mobilities The velocity of the electroosmotic flow, uo can be written as: uo = μoE where μo is the electroosmotic mobility, which is defined as: where ζ is the zeta potential of the capillary wall, and ε is the relative permittivity of the buffer solution. Experimentally, the electroosmotic mobility can be determined by measuring the retention time of a neutral analyte.[3] The velocity (u) of an analyte in an electric field can then be defined as: up + uo = (μp + μo)E Since the electroosmotic flow of the buffer solution is generally greater than that of the electrophoretic flow of the analytes, all analytes are carried along with the buffer solution toward the cathode. Even small, triply charged anions can be redirected to the cathode by the relatively powerful EOF of the buffer solution. Negatively charged analytes are retained longer in the capilliary due to their conflicting electrophoretic mobilities.[2] The order of migration seen by the detector is shown in figure 3: small multiply charged cations migrate quickly and small multiply charged anions are retained strongly.[3] Electroosmotic flow is observed when an electric field is applied to a solution in a capillary that has fixed charges on its interior wall. Charge is accumulated on the inner surface of a capillary when a buffer solution is placed inside the capillary. In a fused-silica capillary, silanol (Si-OH) groups attached to the interior wall of the capillary are ionized to negatively charged silanoate (Si-O-) groups at pH values greater than three. The ionization of the capillary wall can be enhanced by first running a basic solution, such as NaOH or KOH through the capillary prior to introducing the buffer solution. Attracted to the negatively charged silanoate groups, the positively charged cations of the buffer solution will form two inner layers of cations (called the diffuse double layer or the electrical double layer) on the capillary wall as shown in figure 4. The first layer is referred to as the fixed layer because it is held tightly to the silanoate groups. The outer layer, called the mobile layer, is farther from the silanoate groups. The mobile cation layer is pulled in the direction of the negatively charged cathode when an electric field is applied. Since these cations are solvated, the bulk buffer solution migrates with the mobile layer, causing the electroosmotic flow of the buffer solution. Other capillaries including Teflon capillaries also exhibit electroosmotic flow. The EOF of these capillaries is probably the result of adsorption of the electrically charged ions of the buffer onto the capillary walls.[2] The rate of EOF is dependent on the field strength and the charge density of the capillary wall. The wall's charge density is proportional to the pH of the buffer solution. The electroosmotic flow will increase with pH until all of the available silanols lining the wall of the capillary are fully ionized.[3] Figure 4: Depiction of the interior of a fused-silica gel capillary in the presence of a buffer solution. [edit] Efficiency and resolution The number of theoretical plates, or separation efficiency, in capillary electrophoresis is given by: where N is the number of theoretical plates, μ is the apparent mobility in the separation medium and Dm is the diffusion coefficient of the analyte. According to this equation, the efficiency of separation is only limited by diffusion and is proportional to the strength of the electric field. The efficiency of capillary electrophoresis separations is typically much higher than the efficiency of other separation techniques like HPLC. Unlike HPLC, in capillary electrophoresis there is no mass transfer between phases.[3] In addition, the flow profile in EOF-driven systems is flat, rather than the rounded laminar flow profile characteristic of the pressure-driven flow in chromatography columns as shown in figure 5. As a result, EOF does not significantly contribute to band broadening as in pressure-driven chromatography. Capillary electrophoresis separations can have several hundred thousand theoretical plates.[5] Figure 5: Flow profiles of laminar and electroosmotic flow. The resolution (Rs) of capillary electrophoresis separations can be written as: According to this equation, maximum resolution is reached when the electrophoretic and electroosmotic mobilities are similar in magnitude and opposite in sign. In addition, it can be seen that high resolution requires lower velocity and, correspondingly, increased analysis time.[3] Nephelometry This technique is widely used in clinical laboratories because it is relatively easily automated. It is based on the principle that a dilute suspension of small particles will scatter light (usually a laser) passed through it rather than simply absorbing it. The amount of scatter is determined by collecting the light at an angle (usually about 70 or 75 degrees). Antibody and the antigen are mixed in concentrations such that only small aggregates are formed that do not quickly settle to the bottom. The amount of light scatter is measured and compared to the amount of scatter from known mixtures. The amount of the unknown is determined from a standard curve. the PCR Advances in molecular biology during the past decade have yielded a number of practical applications for diagnosing infectious and genetic disease. Polymerase chain reaction (PCR) refers to an in vitro enzymatic amplification of defined DNA sequences, which serves as specific markers for microorganisms or genetic alterations of interest. The major advantages of PCR are the ability to utilize minute samples to produce a high yield of amplified target DNA, the specificity of the reaction, the flexibility of the method, and the simplicity and speed of the automated procedure. Nowadays PCR is one of the most sensitive, specific and versatile laboratory methods. Reliability, possibility to obtain results within 24 hours of receipt of a specimen and cost-effectiveness render PCR a method of choice for laboratory diagnosis of diseases in 21st century.

Principle of the PCR The purpose of a PCR (Polymerase Chain Reaction) is to make a huge number of copies of a gene. This is necessary to have enough starting template for sequencing. 1.	The cycling reactions : There are three major steps in a PCR, which are repeated for 30 or 40 cycles. This is done on an automated cycler, which can heat and cool the tubes with the reaction mixture in a very short time. 1.	Denaturation at 94°C : During the denaturation, the double strand melts open to single stranded DNA, all enzymatic reactions stop (for example : the extension from a previous cycle). 2.	Annealing at 54°C : The primers are jiggling around, caused by the Brownian motion. Ionic bonds are constantly formed and broken between the single stranded primer and the single stranded template. The more stable bonds last a little bit longer (primers that fit exactly) and on that little piece of double stranded DNA (template and primer), the polymerase can attach and starts copying the template. Once there are a few bases built in, the ionic bond is so strong between the template and the primer, that it does not break anymore. 3.	extension at 72°C : This is the ideal working temperature for the polymerase. The primers, where there are a few bases built in, already have a stronger ionic attraction to the template than the forces breaking these attractions. Primers that are on positions with no exact match, get loose again (because of the higher temperature) and don't give an extension of the fragment. The bases (complementary to the template) are coupled to the primer on the 3' side (the polymerase adds dNTP's from 5' to 3', reading the template from 3' to 5' side, bases are added complementary to the template) Because both strands are copied during PCR, there is an exponential increase of the number of copies of the gene. Suppose there is only one copy of the wanted gene before the cycling starts, after one cycle, there will be 2 copies, after two cycles, there will be 4 copies, three cycles will result in 8 copies and so on.

Figure 3 : The different steps in PCR. (pdf file of this picture) 2.	Is there a gene copied during PCR and is it the right size ? Before the PCR product is used in further applications, it has to be checked if : 1.	There is a product formed. Though biochemistry is an exact science, not every PCR is successful. There is for example a possibility that the quality of the DNA is poor, that one of the primers doesn't fit, or that there is too much starting template 2.	The product is of the right size It is possible that there is a product, for example a band of 500 bases, but the expected gene should be 1800 bases long. In that case, one of the primers probably fits on a part of the gene closer to the other primer. It is also possible that both primers fit on a totally different gene. 3.	Only one band is formed. As in the description above, it is possible that the primers fit on the desired locations, and also on other locations. In that case, you can have different bands in one lane on a gel.

Figure 5 : Verification of the PCR product on gel. The ladder is a mixture of fragments with known size to compare with the PCR fragments. Notice that the distance between the different fragments of the ladder is logarithmic. Lane 1 : PCR fragment is approximately 1850 bases long. Lane 2 and 4 : the fragments are approximately 800 bases long. Lane 3 : no product is formed, so the PCR failed. Lane 5 : multiple bands are formed because one of the primers fits on different places. Analytical sensitivity of the PCR is high enough to detect 10-100 copies of the DNA sequence of interest and make out reliable diagnosis, wheras conventional microbiological and immunological methods require at least 103 - 105 microorganisms to be present in the sample. PCR represents an important breakthrough of molecular technology from the research to the clinical laboratory. PCR is an extremely useful adjunct to contemporary laboratory diagnostic techniques. PCR lifts lots of restrictions characteristic for other methods

Northern blot From Wikipedia, the free encyclopedia Jump to: navigation, search The northern blot is a technique used in molecular biology research to study gene expression. It takes its name from its similarity to the Southern blot technique, named for biologist Edwin Southern. The major difference is that RNA, rather than DNA, is analyzed in the northern blot. Both techniques use electrophoresis and detection with a hybridization probe. The northern blot technique was developed in 1977 by James Alwine, David Kemp, and George Stark at Stanford University.[1] The gels may be run on either agarose or denaturing polyacrylamide, the latter being preferable for smaller fragments of RNA. Unlike in the Southern blot, formaldehyde is added to the gel and acts as a denaturant to agarose. For polyacrylamide, urea is the denaturant. As in the Southern blot, the hybridization probe may be made from DNA or RNA. A variant of the procedure known as the reverse northern blot is occasionally used. In this procedure, the substrate nucleic acid (that is affixed to the membrane) is a collection of isolated DNA fragments, and the probe is RNA extracted from a tissue and radioactively labelled. The use of DNA microarrays that have come into widespread use in the late 1990s and early 2000s is more akin to the reverse procedure, in that they involve the use of isolated DNA fragments affixed to a substrate, and hybridization with a probe made from cellular RNA. Thus the reverse procedure, though originally uncommon, enabled northern analysis to evolve into gene expression profiling, in which many (possibly all) of the genes in an organism may have their expression monitored.

Southern blot From Wikipedia, the free encyclopedia Jump to: navigation, search A Southern blot is a method routinely used in molecular biology to check for the presence of a DNA sequence in a DNA sample. Southern blotting combines agarose gel electrophoresis for size separation of DNA with methods to transfer the size-separated DNA to a filter membrane for probe hybridization. The method is named after its inventor, the British biologist Edwin Southern.[1] Other blotting methods (i.e., western blot, northern blot, southwestern blot) that employ similar principles, but using RNA or protein, have later been named in reference to Southern's name. As the technique was eponymously named, Southern blot should be capitalized, whereas northern and western blots should not.[citation needed] Method 1.	Restriction endonucleases are used to cut high-molecular-weight DNA strands into smaller fragments. 2.	The DNA fragments are then electrophoresed on an agarose gel to separate them by size. 3.	If some of the DNA fragments are larger than 15 kb, then prior to blotting, the gel may be treated with an acid, such as dilute HCl, which depurinates the DNA fragments, breaking the DNA into smaller pieces, thus allowing more efficient transfer from the gel to membrane. 4.	If alkaline transfer methods are used, the DNA gel is placed into an alkaline solution (typically containing sodium hydroxide) to denature the double-stranded DNA. The denaturation in an alkaline environment provides for improved binding of the negatively charged DNA to a positively charged membrane, separates it into single DNA strands for later hybridization to the probe (see below), and destroys any residual RNA that may still be present in the DNA. 5.	A sheet of nitrocellulose (or, alternatively, nylon) membrane is placed on top of (or below, depending on the direction of the transfer) the gel. Pressure is applied evenly to the gel (either using suction, or by placing a stack of paper towels and a weight on top of the membrane and gel), to ensure good and even contact between gel and membrane. Buffer transfer by capillary action from a region of high water potential to a region of low water potential (usually filter paper and paper tissues) is then used to move the DNA from the gel on to the membrane; ion exchange interactions bind the DNA to the membrane due to the negative charge of the DNA and positive charge of the membrane. 6.	The membrane is then baked, i.e., exposed to high temperature (60 to 100 °C) (in the case of nitrocellulose) or exposed to ultraviolet radiation (nylon) to permanently and covalently crosslink the DNA to the membrane. 7.	The membrane is then exposed to a hybridization probe—a single DNA fragment with a specific sequence whose presence in the target DNA is to be determined. The probe DNA is labelled so that it can be detected, usually by incorporating radioactivity or tagging the molecule with a fluorescent or chromogenic dye. In some cases, the hybridization probe may be made from RNA, rather than DNA. To ensure the specificity of the binding of the probe to the sample DNA, most common hybridization methods use salmon testes (sperm) DNA for blocking of the membrane surface and target DNA, deionized formamide, and detergents such as SDS to reduce non-specific binding of the probe. 8.	After hybridization, excess probe is washed from the membrane, and the pattern of hybridization is visualized on X-ray film by autoradiography in the case of a radioactive or fluorescent probe, or by development of color on the membrane if a chromogenic detection method is used. Result Hybridization of the probe to a specific DNA fragment on the filter membrane indicates that this fragment contains DNA sequence that is complementary to the probe. The transfer step of the DNA from the electrophoresis gel to a membrane permits easy binding of the labeled hybridization probe to the size-fractionated DNA. It also allows for the fixation of the target-probe hybrids, required for analysis by autoradiography or other detection methods. Southern blots performed with restriction enzyme-digested genomic DNA may be used to determine the number of sequences (e.g., gene copies) in a genome. A probe that hybridizes only to a single DNA segment that has not been cut by the restriction enzyme will produce a single band on a Southern blot, whereas multiple bands will likely be observed when the probe hybridizes to several highly similar sequences (e.g., those that may be the result of sequence duplication). Modification of the hybridization conditions (for example, increasing the hybridization temperature or decreasing salt concentration) may be used to increase specificity and decrease hybridization of the probe to sequences that are less than 100% similar. Western blot

A Western blot. The western blot (alternatively, immunoblot) is an analytical technique used to detect specific proteins in a given sample of tissue homogenate or extract. It uses gel electrophoresis to separate native or denatured proteins by the length of the polypeptide (denaturing conditions) (Figure 1) or by the 3-D structure of the protein (native/ non-denaturing conditions). The proteins are then transferred to a membrane (typically nitrocellulose or PVDF), where they are probed (detected) using antibodies specific to the target protein. There are now many reagent companies that specialize in providing antibodies (both monoclonal and polyclonal antibodies) against many thousands of different proteins. Commercial antibodies can be expensive, although the unbound antibody can be reused between experiments. This method is used in the fields of molecular biology, biochemistry, immunogenetics and other molecular biology disciplines. Other related techniques include using antibodies to detect proteins in tissues and cells by immunostaining and enzyme-linked immunosorbent assay (ELISA). The method originated from the laboratory of George Stark at Stanford. The name western blot was given to the technique by W. Neal Burnette[1] and is a play on the name Southern blot, a technique for DNA detection developed earlier by Edwin Southern. Detection of RNA is termed northern blotting. Steps in a Western blot Tissue preparation Samples may be taken from whole tissue or from cell culture. In most cases, solid tissues are first broken down mechanically using a blender (for larger sample volumes), using a homogenizer (smaller volumes), or by sonication. Cells may also be broken open by one of the above mechanical methods. However, it should be noted that bacteria, virus or environmental samples can be the source of protein and thus Western blotting is not restricted to cellular studies only. Assorted detergents, salts, and buffers may be employed to encourage lysis of cells and to solubilize proteins. Protease and phosphatase inhibitors are often added to prevent the digestion of the sample by its own enzymes. A combination of biochemical and mechanical techniques – including various types of filtration and centrifugation – can be used to separate different cell compartments and organelles. Gel electrophoresis Main article: Gel electrophoresis

Immunoblot (Western blot) analysis of proteins separated by SDS-PAGE gradientgel electrophoresis.[2] The proteins of the sample are separated using gel electrophoresis. Separation of proteins may be by isoelectric point (pI), molecular weight, electric charge, or a combination of these factors. The nature of the separation depends on the treatment of the sample and the nature of the gel. By far the most common type of gel electrophoresis employs polyacrylamide gels and buffers loaded with sodium dodecyl sulfate (SDS). SDS-PAGE (SDS polyacrylamide gel electrophoresis) maintains polypeptides in a denatured state once they have been treated with strong reducing agents to remove secondary and tertiary structure (e.g. disulfide bonds [S-S] to sulfhydryl groups [SH and SH]) and thus allows separation of proteins by their molecular weight. Sampled proteins become covered in the negatively charged SDS and move to the positively charged electrode through the acrylamide mesh of the gel. Smaller proteins migrate faster through this mesh and the proteins are thus separated according to size (usually measured in kilo Daltons, kDa). The concentration of acrylamide determines the resolution of the gel - the greater the acrylamide concentration the better the resolution of lower molecular weight proteins. The lower the acrylamide concentration the better the resolution of higher molecular weight proteins. Proteins travel only in one dimension along the gel for most blots. Samples are loaded into wells in the gel. One lane is usually reserved for a marker or ladder, a commercially available mixture of proteins having defined molecular weights, typically stained so as to form visible, coloured bands. When voltage is applied along the gel, proteins migrate into it at different speeds. These different rates of advancement (different electrophoretic mobilities) separate into bands within each lane. It is also possible to use a two-dimensional (2-D) gel which spreads the proteins from a single sample out in two dimensions. Proteins are separated according to isoelectric point (pH at which they have neutral net charge) in the first dimension, and according to their molecular weight in the second dimension. Transfer In order to make the proteins accessible to antibody detection, they are moved from within the gel onto a membrane made of nitrocellulose or polyvinylidene difluoride (PVDF). The membrane is placed on top of the gel, and a stack of tissue papers placed on top of that. The entire stack is placed in a buffer solution which moves up the paper by capillary action, bringing the proteins with it. Another method for transferring the proteins is called electroblotting and uses an electric current to pull proteins from the gel into the PVDF or nitrocellulose membrane. The proteins move from within the gel onto the membrane while maintaining the organization they had within the gel. As a result of this "blotting" process, the proteins are exposed on a thin surface layer for detection (see below). Both varieties of membrane are chosen for their non-specific protein binding properties (i.e. binds all proteins equally well). Protein binding is based upon hydrophobic interactions, as well as charged interactions between the membrane and protein. Nitrocellulose membranes are cheaper than PVDF, but are far more fragile and do not stand up well to repeated probings. The uniformity and overall effectiveness of transfer of protein from the gel to the membrane can be checked by staining the membrane with Coomassie or Ponceau S dyes. Coomassie is the more sensitive of the two, although Ponceau S's water solubility makes it easier to subsequently destain and probe the membrane as described below. Blocking Since the membrane has been chosen for its ability to bind protein, and both antibodies and the target are proteins, steps must be taken to prevent interactions between the membrane and the antibody used for detection of the target protein. Blocking of non-specific binding is achieved by placing the membrane in a dilute solution of protein - typically Bovine serum albumin (BSA) or non-fat dry milk (both are inexpensive), with a minute percentage of detergent such as Tween 20. The protein in the dilute solution attaches to the membrane in all places where the target proteins have not attached. Thus, when the antibody is added, there is no room on the membrane for it to attach other than on the binding sites of the specific target protein. This reduces "noise" in the final product of the Western blot, leading to clearer results, and eliminates false positives. Detection During the detection process the membrane is "probed" for the protein of interest with a modified antibody which is linked to a reporter enzyme, which when exposed to an appropriate substrate drives a colourimetric reaction and produces a colour. For a variety of reasons, this traditionally takes place in a two-step process, although there are now one-step detection methods available for certain applications. Two step ·	Primary antibody Antibodies are generated when a host species or immune cell culture is exposed to the protein of interest (or a part thereof). Normally, this is part of the immune response, whereas here they are harvested and used as sensitive and specific detection tools that bind the protein directly. After blocking, a dilute solution of primary antibody (generally between 0.5 and 5 micrograms/ml) is incubated with the membrane under gentle agitation. Typically, the solution is composed of buffered saline solution with a small percentage of detergent, and sometimes with powdered milk or BSA. The antibody solution and the membrane can be sealed and incubated together for anywhere from 30 minutes to overnight. It can also be incubated at different temperatures, with warmer temperatures being associated with more binding, both specific (to the target protein, the "signal") and non-specific ("noise"). ·	Secondary antibody After rinsing the membrane to remove unbound primary antibody, the membrane is exposed to another antibody, directed at a species-specific portion of the primary antibody. This is known as a secondary antibody, and due to its targeting properties, tends to be referred to as "anti-mouse," "anti-goat," etc. Antibodies come from animal sources (or animal sourced hybridoma cultures); an anti-mouse secondary will bind to just about any mouse-sourced primary antibody. This allows some cost savings by allowing an entire lab to share a single source of mass-produced antibody, and provides far more consistent results. The secondary antibody is usually linked to biotin or to a reporter enzyme such as alkaline phosphatase or horseradish peroxidase. This means that several secondary antibodies will bind to one primary antibody and enhances the signal. Most commonly, a horseradish peroxidase-linked secondary is used in conjunction with a chemiluminescent agent, and the reaction product produces luminescence in proportion to the amount of protein. A sensitive sheet of photographic film is placed against the membrane, and exposure to the light from the reaction creates an image of the antibodies bound to the blot. As with the ELISPOT and ELISA procedures, the enzyme can be provided with a substrate molecule that will be converted by the enzyme to a colored reaction product that will be visible on the membrane (see the figure below with blue bands). A third alternative is to use a radioactive label rather than an enzyme coupled to the secondary antibody, such as labeling an antibody-binding protein like Staphylococcus Protein A with a radioactive isotope of iodine. Since other methods are safer, quicker and cheaper this method is now rarely used. One step Historically, the probing process was performed in two steps because of the relative ease of producing primary and secondary antibodies in separate processes. This gives researchers and corporations huge advantages in terms of flexibility, and adds an amplification step to the detection process. Given the advent of high-throughput protein analysis and lower limits of detection, however, there has been interest in developing one-step probing systems that would allow the process to occur faster and with less consumables. This requires a probe antibody which both recognizes the protein of interest and contains a detectable label, probes which are often available for known protein tags. The primary probe is incubated with the membrane in a manner similar to that for the primary antibody in a two-step process, and then is ready for direct detection after a series of wash steps.

Western blot using radioactive detection system [edit] Analysis After the unbound probes are washed away, the western blot is ready for detection of the probes that are labeled and bound to the protein of interest. In practical terms, not all westerns reveal protein only at one band in a membrane. Size approximations are taken by comparing the stained bands to that of the marker or ladder loaded during electrophoresis. The process is repeated for a structural protein, such as actin or tubulin, that should not change between samples. The amount of target protein is indexed to the structural protein to control between groups. This practice ensures correction for the amount of total protein on the membrane in case of errors or incomplete transfers. [edit] Colorimetric detection The colorimetric detection method depends on incubation of the western blot with a substrate that reacts with the reporter enzyme (such as peroxidase) that is bound to the secondary antibody. This converts the soluble dye into an insoluble form of a different color that precipitates next to the enzyme and thereby stains the membrane. Development of the blot is then stopped by washing away the soluble dye. Protein levels are evaluated through densitometry (how intense the stain is) or spectrophotometry. [edit] Chemiluminescent detection Chemiluminescent detection methods depend on incubation of the western blot with a substrate that will luminesce when exposed to the reporter on the secondary antibody. The light is then detected by photographic film, and more recently by CCD cameras which captures a digital image of the western blot. The image is analysed by densitometry, which evaluates the relative amount of protein staining and quantifies the results in terms of optical density. Newer software allows further data analysis such as molecular weight analysis if appropriate standards are used. So-called "enhanced chemiluminescent" (ECL) detection is considered to be among the most sensitive detection methods for blotting analysis. Radioactive detection Radioactive labels do not require enzyme substrates, but rather allow the placement of medical X-ray film directly against the western blot which develops as it is exposed to the label and creates dark regions which correspond to the protein bands of interest (see image to the right). The importance of radioactive detections methods is declining[citation needed], because it is very expensive, health and safety risks are high and ECL provides a useful alternative. Fluorescent detection The fluorescently labeled probe is excited by light and the emission of the excitation is then detected by a photosensor such as CCD camera equipped with appropriate emission filters which captures a digital image of the western blot and allows further data analysis such as molecular weight analysis and a quantitative western blot analysis. Fluorescence is considered to be among the most sensitive detection methods for blotting analysis. Secondary probing One major difference between nitrocellulose and PVDF membranes relates to the ability of each to support "stripping" antibodies off and reusing the membrane for subsequent antibody probes. While there are well-established protocols available for stripping nitrocellulose membranes, the sturdier PVDF allows for easier stripping, and for more reuse before background noise limits experiments. Another difference is that, unlike nitrocellulose, PVDF must be soaked in 95% ethanol, isopropanol or methanol before use. PVDF membranes also tend to be thicker and more resistant to damage during use. 2-D Gel Electrophoresis Main article: Two-dimensional gel electrophoresis 2-dimensional SDS-PAGE uses the principles and techniques outlined above. 2-D SDS-PAGE, as the name suggests, involves the migration of polypeptides in 2 dimensions. For example, in the first dimension polypeptides are separated according to isoelectric point, while in the second dimension polypeptides are separated according to their molecular weight. The isoelectric point of a given protein is determined by the relative number of positively (e.g. lysine and arginine) and negatively (e.g. glutamate and aspartate) charged amino acids, with negatively charged amino acids contributing to a high isoelectric point and positively charged amino acids contributing to a low isoelectric point. Samples could also be separated first under nonreducing conditions using SDS-PAGE and under reducing conditions in the second dimension, which breaks apart disulfide bonds that hold subunits together. SDS-PAGE might also be coupled with urea-PAGE for a 2-dimensional gel. In principle, this method allows for the separation of all cellular proteins on a single large gel. A major advantage of this method is that it often distinguishes between different isoforms of a particular protein - e.g. a protein that has been phosphorylated (by addition of a negatively charged group). Proteins that have been separated can be cut out of the gel and then analysed by mass spectrometry, which identifies the protein. Please refer to reference articles for examples of the application of 2-D SDS PAGE. Medical diagnostic applications ·	The confirmatory HIV test employs a Western blot to detect anti-HIV antibody in a human serum sample. Proteins from known HIV-infected cells are separated and blotted on a membrane as above. Then, the serum to be tested is applied in the primary antibody incubation step; free antibody is washed away, and a secondary anti-human antibody linked to an enzyme signal is added. The stained bands then indicate the proteins to which the patient's serum contains antibody. ·	A Western blot is also used as the definitive test for Bovine spongiform encephalopathy (BSE, commonly referred to as 'mad cow disease'). ·	Some forms of Lyme disease testing employ Western blotting.