PHYSICS NEWS UPDATE
The American Institute of Physics Bulletin of Physics News
Number 627 March 7, 2003   by Phillip F. Schewe, Ben Stein, and James
Riordon

MICROFLUIDICS is a traffic control system for sampling, sorting, and mixing
mesocopic objects.  The objects are often biological---cells, proteins,
chromosomes in a solvent---and the platform is often a lithographically
patterned chip on which fluids are urged through microchannels using volts,
heat, or even peristaltic pressure.  Microfluidics was a large topic at this
week's March Meeting of the American Physical Society (APS) in Austin, Texas
(http://www.aps.org/meet/MAR03/baps/index.html ).  Here are some
highlights.
Carl Hansen (Caltech) described a device with the largest degree of
integration yet achieved: a chip with 1000 250-picoliter chambers with
attendant valves for controlling flow and mixing (see also Science, 18
October 2002).  Another device in the Caltech lab of Stephen Quake allows
the careful metering of reagents in order to facilitate protein
crystallization under a variety of conditions (pH, viscosity, surface
tension, 48 different solvents, etc.) on a huge scale (144 parallel
reactions can take place) and with a minimum of means---only 10 nl of
precious protein samples are needed, 100 times less than with usual methods
(see also Proc. Natl. Acad. Sci., 24 Dec 2002).  In this way, many proteins
have been turned into crystals, often in the space of hours rather than
days.  Indeed some protein species were crystallized for the first time.
The crystals can then be bombarded with x rays in order to determine
molecular structure.
David Grier (Univ. Chicago) reported on a method called holographic optical
tweezers, in which a beam of laser light, sent into a hologram, is divided
into a myriad of sub-beams which can  independently suspend and manipulate
numerous tiny objects for possible transportation, mixing, or reacting.
Grier showed movies of ensembles of micro-spheres moved into patterns and
even set to spinning by the holographically sculpted light fields.  Applied
to fluid samples of biomolecules, the holographic multiplexing produces what
Grier calls "optical fractionation," an optical equivalent of gel
electrophoresis, in which electric fields are used differentially to drive
and separate macromolecules.  In the flexible Chicago approach, there is no
viscous gel, and a deft change in the computer-generated hologram or the
laser wavelength can quickly bring about sorting of objects ranging from the
100-nm size (viruses) up to the 100-micron size scale.
Meanwhile, Jochen Guck (Univ. Leipzig) subjects fluid-borne cells to a pair
of laser beams which stretch the cells and probe their elasticity.  In
general sick cells are softer (by a factor of 2 to 10) than healthy cells.
In this way, Guck's "optical stretcher" can "feel" the
difference between
normal and abnormal at a rate of hundreds of cells per hour, compared to
typical rates of 10 cells per day using other elasticity-measuring methods,
thus reducing the need for biopsies requiring larger tissue samples.  The
Leipzig device might even be able to tell the difference between ordinary
cancerous cells from the even softer metastasizing-capable cells.

THE SEARCH FOR AN RNA "EVE," a hypothetical ancestor of some or all of the
types of RNA now known, might be possible using a technique pioneered by
scientists at MIT's Whitehead Institute.  Just as DNA samples are used by
paleo-anthropologists to study the spread of humans to different part of the
world, and by evolutionary biologists to study connections among various
lineages on the tree of living organisms, so too there might be ways of
studying the origins of RNA, or at least the relation between RNA foldedness
and biochemical function.  Unlike DNA, its double-stranded cousin, RNA
starts out single-stranded, but can at many places along its length double
over on itself to arrive at complicated, twisted shapes.
Speaking at the APS March Meeting, Erik Schultes (MIT-Whitehead) reported
on an experiment in which a particular sequence of RNA bases could, by
altering one base at a time, take on rather quickly the identity of either
of two very different ribozymes (RNA molecules that can catalyze reactions)
with two very different functions, one for cleavage and one for ligation.
Continuing to substitute different bases in a clever way, the researchers
noticed that they could retain the functionality of the two RNA species
(that is, the ribozymes went on performing their cleavage or ligation jobs)
even though the two were getting progressively further apart in "sequence
space."  At the end one could look at the two contrasting ribozymes, with
different function and very different sequences, and hardly suspect that
they had a common origin.   Schultes (schultes{at}wi.mit.edu) compared this to
transforming the word cat into the word dog through a sequence of
single-letter "mutations," each one of which resulted in a legitimate word:
cat-cot-cog-dog (for background see Science, 21 July 2000).
At the same RNA session Ranjan Mukhopadhyay (ranjan{at}research.nj.nec.com)
reported that he and his colleagues at NEC Laboratories in New Jersey have
found that a typical RNA sequence with its 4-base chemical code folds more
predictably and stably than would hypothetical RNA sequences based on a
two-base or six-base "alphabet.  Both 4-base and 6-base RNA proved to be
more stable than 2-base RNA.  Furthermore, 4-base RNA possessed more stable,
foldable structures than 6-base RNA (just as it is easier to form 4-letter
Scrabble words than it is to form 6-letter words).
In other theoretical work, Ralf Bundschuh of Ohio State
(bundschuh{at}mps.ohio-state.edu) and Terence Hwa of UC-San Diego have
showed that RNA could exhibit several different "phases," just as water can
exist on a pressure-versus-temperature phase diagram in the solid, gaseous,
or liquid forms.  In the case of RNA, Bundschuh showed mathematically, RNA
could exist in a normal, glassy, molten, or denatured phase.  At low
temperatures, for instance, in the "glassy" phase, a given RNA sequence can
get stuck in a random structure. At higher temperatures, RNA can assume a
more flexible molten state, in which it is free to fold into a variety of
different shapes.

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