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F

EBRUARY

2003 T

ODAY


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HEMIST AT

W

ORK



63

©2003 A


MERICAN

C

HEMICAL



S

OCIETY


PH

O

TO COURTES



Y OF THE SVEDBERG LABORA

TORY


, UPPS

ALA UNIVERSITY

, UPPS

ALA, SWEDEN



T

he history of the development of

the ultracentrifuge is a story of

the intersection of basic physics and

practical chemistry with results that helped

create the field of molecular biology. The

ultracentrifuge can generate forces thou-

sands or millions of times stronger than

the force of gravity. The develop-

ment of this class of devices permit-

ted the fractionation of subcellu-

lar bodies previously visible only

through an electron microscope.

This in turn facilitated the analy-

sis of their enzymatic and molec-

ular constituents, providing infor-

mation about structure and

function.



On the Centrifuge

The simplest centrifuge is a rotor

mounted on a shaft and powered

by an external device. Common

examples include an electric fan

or the wheels of a car. Other exam-

ples include windmills, in which

moving air drives a shaft-mount-

ed rotor, or waterwheels, in which water

does the same thing.

But these simple centrifuges, and small-

scale models used in the laboratory, have

some serious drawbacks that stem from

the basic physics of a shaft-mounted rotor.

Spinning shaft-mounted rotors at speeds

greater than a few hundred revolutions

per second (rps) cause a problem much

like wheel imbalance in a car. But where

a car’s wheels rotate at perhaps only 10

rps even at freeway speeds, the rotor of

a centrifuge can turn at several hundred

(or more) rps. At those rates, the inabil-

ity to make the inertial axis of the rotor

match exactly the axis of its motive

shaft becomes problematic, and the rotor

shakes uncontrollably.

Carl de Laval, a Swedish engineer, over-

came some of these limitations in 1883,

when he introduced a turbine that featured

a steam-powered rotor on a flexible shaft.

This shaft was able to shift under the force

of the imbalance and could turn at sever-

al hundred rps.

In addition to the mismatch between

the axial rotation of the rotor and the shaft,

there were other drawbacks and limitations

of this technology that only became appar-

ent with the discovery of the large macro-

molecules. The slower speeds necessary to

keep the centrifuge from shaking itself

apart were too slow to separate the macro-

molecules that increasingly drew the atten-

tion of biologists, chemists, and physi-

cists after Friedrich Miescher isolated DNA.

But spinning the centrifuges at speeds

high enough to separate macromolecules

would cause the centrifuge to break apart

under the influence of the forces it gener-

ated, sometimes forcefully.

Svedberg and the Ultracentrifuge

In the 1920s, Theodor H. E. Svedberg at

Upsalla University became interested in

the problems of centrifugation through

chemistry. Svedberg was a colloid chemist.

His doctoral dissertation described a new

method of producing colloid particles and

provided convincing proof of a theory by

Albert Einstein and Marian Smoluchowski

concerning Brownian motion, which provid-

ed proof of the existence of molecules. With

several collaborators, Svedberg went on

to investigate the properties of colloids,

including diffusion, light absorption, and

sedimentation.

It was through his studies of colloid

sedimentation that Svedberg came to invent

the first of the ultracentrifuges, centrifuges

that operated at thousands of rps

and were powerful enough to sepa-

rate even macromolecules.

Svedberg developed his ultra-

centrifuges in the 1920s in the

hopes that they might yield the

answer to what was at the time

thought to be the key to colloid

solutions: the distribution of parti-

cle size. In the ultracentrifuge, large

molecules such as proteins and

carbohydrates were spun fast

enough to subject them to thou-

sands of times the force of gravity,

ultimately up to about 10

6

g. This



was in 1925–1926. 

Svedberg and Alf Lysholm at

Uppsala later constructed a

centrifuge with a maximum speed

of 42,000 rpm. Svedberg’s initial high-speed

centrifuges were small, with the rotor

mounted on a nonflexible shaft. Their speeds

topped out around 1000 rps in a normal

atmosphere. However, when the rotor was

housed in a low-pressure hydrogen atmos-

phere, he was able to subject colloid and

other samples to forces up to a million times

that of gravity.

The protein–colloid solutions Sved-

berg wished to study were enclosed in plane

parallel rock crystal cells. Each such setup

was covered with a layer of vacuum oil and

placed in a rotor mounted atop a vertical

shaft, which was equipped with a ther-

mocouple-controlled cooling system. The

rotor was enclosed in a hydrogen atmos-

phere because hydrogen provides much less

friction and equalizes temperature differ-

ences. The housing had two windows for



C h e m i s t r y   C h r o n i c l e s

C

HRISTOPHER

S. W. K

OEHLER

Developing the 

Ultracentrifuge

Throughout the 20th century, a succession 

of researchers contributed to the gravity 

of the situation.

Theodor Svedberg at the Gustav Werner Institute, 1953


a beam of UV light to be shone through

the sample during rotation. Conditions were

detected with a UV camera.

Svedberg’s results convinced him that

proteins were formed by aggregates of a

single very large unit. He thought, wrong-

ly as it turned out, that all proteins were

multiples of this basic unit, which came

to be called “the Svedberg”—which had

a molecular weight of 17,500 Da. Using

his ultracentrifuge techniques, Svedberg

calculated the molecular weights of hemo-

globin and casein. By the end of the 1920s,

his research, which had earned him a Nobel

Prize in chemistry in 1926, headed in

the direction of biomolecular surveys

and molecular measurements of phyloge-

netic relationships. 



Beams and the Ultracentrifuge

Jessie Beams, an American physicist asso-

ciated with the University of Virginia (UVA),

was interested in high-speed centrifuga-

tion as well. The centrifuge design Beams

was familiar with was startlingly different

from that developed by Svedberg. Two

Belgian scientists, E. Henriot and E. Hugue-

nard, had developed a shaftless centrifuge.

Its rotor was driven by air and suspended

in space by a jet of air. Gone was the shaft

and so gone was the problem of mismatch

between the axial rotations. Shaftless rotors

as small as an inch in diameter were free

to spin up to 4000 rps. The primary drag

on speed was atmospheric friction.

As a young researcher at UVA, Beams

contemplated the new applications for the

technology that could result if the drag on

the rotational speed could be eliminated:

eliminate or reduce the drag and rotational

speeds of a million or more rps might be

possible. As a result, he concentrated his

research and design efforts on drag factors.

Beams realized that his rotors would

have to be enclosed in a high vacuum if

his ultracentrifuge was to overcome the

limitations of previous designs, like those

pioneered by Svedberg. His first designs

featured rotors suspended in a vacuum from

a flexible shaft. The shaft passed through

an oil seal to attach to an air-driven turbine.

Like the early system of de Laval, this flex-

ible shaft allowed the rotor to spin about

its own inertial axis. This design was

obviously far from frictionless, but it avoid-

ed the problem of frictional sample heat-

ing and it permitted rotors up to a foot in

diameter to spin at thousands of rps.

Although useful—Beams in 1961

described this type of centrifuge as the

“workhorse” of molecular sedimentation

experiments—this was not the ultimate

ultracentrifuge Beams sought and knew

could be designed. Rather, he was look-

ing for a centrifuge in which the tensile

strength of the rotor alone limited the rate

of spin. To reach this, the vacuum would

have to be strong and there could be no

supporting shaft.

In the mid-1930s, Beams experiment-

ed with magnetic fields to support the

rotor. The field generated by an external

electromagnet could lift a rotor made of

ferromagnetic material. Such a rotor would

spin freely and seek to rotate unimpeded

about its own inertial axis.

Beams hung the electromagnet by a

flexible wire so that the ferromagnetic rotor

could pull the axis of the electromagnet-

ic field in line with its own axis of rota-

tion, stabilizing the spin axis at very

high speeds.

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Another problem remained. Such a rotor

could range up and down that vertical axis

if the balance between the magnetic field

and gravitational pull was not maintained.

Beams’ solution was ingenious. He flashed

a beam of light across the rotor to a photo-

electric cell. If the rotor deviated, the light

hitting the photoelectric cell would change

in such a way that it produced a corre-

sponding current in the electromagnet.

This then corrected the rotor position.

With the rotor in its evacuated cham-

ber stabilized by external fields, the

ultracentrifuge could spin rotors of less

than a thousandth of an inch to more than

a foot, and of weights ranging from a

billionth of a pound to more than a hundred

pounds. The rotor could spin to speeds of

more than a million rps, speeds at which

the rotor could easily explode under

centrifugal forces of more than a billion

times the force of gravity.



Applications and Improvements

A host of workers at many institutions used

these and newer types of ultracentrifuges

to make significant advances. Rockefeller

Foundation money helped to fund Ralph

Wyckoff’s development of an air-driven

ultracentrifuge, a simpler and cheaper

device than Svedberg’s original design,

which was important to the virus studies

of W. M. Stanley, for example. Beams ulti-

mately used the field-supported model to

separate atomic isotopes, contributing to

the development of the atomic bomb. He

also developed ways to establish the

strength of materials by driving the rotors

to explosive speeds. 

Others continued to elaborate on the

basic design. Edward Pickels, one of Beams’

students, developed an ultracentrifuge driv-

en by electricity and helped develop one

of the earliest preparative ultracentrifuges

marketed by Spinco (Specialized Instru-

ments Corp.) which was acquired by Beck-

man in 1955.

The Beckman Model E ultracentrifuge

developed after World War II became the

workhorse for analytical ultracentrifuga-

tion; later, in the 1960s, Yoichiro Ito devel-

oped a centrifuge based on a coil, the

coil planet centrifuge, that led to the devel-

opment of countercurrent chromatography

in the early 1970s. Throughout the latter

half of the 20th century, preparative and

analytical ultracentrifugation took their

places among the key technologies of

modern chemistry, especially the realm of

molecular biology.

Suggested Reading

Haw, M. D. Colloidal suspensions, Brownian motion,

molecular reality: A short history. J. Phys.:

Condens. Matter 2002, 14, 7769–7779.

Instruments of Science; Bud, R., Ed.; The Science

Museum: London, 1998.

Jesse Wakefield Beams biographical memoir;

www.nap.edu/books/0309033918/html/2.html.

Stapleton, D. H. The Past and the Future of

Research in the History of Science, Medicine,

and Technology at the Rockefeller Archive

Center; www.rockefeller.edu/archive.ctr/

brazil.pdf.

Theodor Svedberg Nobel Prize in Chemistry

1926; www.nobel.se/chemistry/laureates/1926/

index.html. 



Christopher S. W. Koehler holds a Ph.D.

in the history of science. He writes and teach-

es in northern California. Send your

comments or questions about this article to

tcaw@acs.org or to the Editorial Office

address on page 3. 

66 T

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