**[Lab-on-a-Chip]{.underline}**

"Lab-on-a-Chip" refers to two different miniature liquid chromatographs
under development at JPL. Like most instruments created for NASA, they
squeeze a lot of technology into very small spaces.

The function of all chromatographs is to separate a mixture of compounds
into its constituent chemicals. But unlike the gas chromatographs used
with the Miniature Mass Spectrometer, the Lab-on-a-Chip liquid
chromatographs don't separate molecules according to how long they stick
to an adsorbent medium. Instead, one device sorts molecules by size, and
the other separates them -- like a mass spectrometer -- by
charge-to-mass ratio.

**The Nanofluidic Size Exclusion Chromatograph**

JPL's nanofluidic size exclusion chromatograph (nano-SEC) is for
analyzing relatively large organic molecules and cell fragments, ranging
from several nanometers to about 100 nm in size.

It separates them by staging a kind of race. Several methods are being
tested, but the general principle can be understood from one in which
the molecules travel through a course much like skiers in a slalom
event. Where real slalom skiers would find individual posts to maneuver
around, however, these molecules find clusters of evenly-spaced posts.
And they finish their race in size order.

Molecules that are larger that the spaces between the posts in each
cluster are not able to enter the clusters, and so cannot spend time
weaving through them. They just bounce off, bypass the clusters, and
cross the finish line in first place.

Molecules that are just about the same size as the spaces between the
posts enter the openings they happen to hit head-on, but are more likely
to bounce off the ones they approach at an angle. So they bypass some
clusters and spend time zigzagging through others. They finish second.

Bringing up the rear are molecules substantially smaller than the spaces
between the posts. Since they have a high probability of entering any
opening they encounter, they trace a circuitous path through most of the
clusters, and reach the finish line after the other molecules have
retired to the lodge to sip hot chocolate.

In a variation on this technique, the liquid sample flows through a
series of progressively smaller channels. As each molecule encounters a
channel through which it cannot fit, it bypasses the rest of the course
and exits the system. So, as in the slalom race, the largest molecules
finish first, the smallest finish last, and the intermediate ones finish
in-between, in diminishing size order.

Whatever method is used to separate them, a detector at the finish line
signals the arrival of each molecule. It turns out that each kind of
chemical takes a characteristic amount of time to move through a
chromatograph. So as each molecule exits, a computer calculates its
transit time and compares it with tables stored in its data bank to
determine the molecule's identity.

A variety of detectors can be used at the end of the labyrinth to
indicate when each molecule has completed its journey. The one currently
under development for the prototype nano-SEC is an electrochemical
detector, which signals a molecule's arrival with a burst of electric
current.

The distinguishing feature of the various nano-SECs is their tiny size.
In the slalom-like system described above, each post is only 20
nanometers wide (a typical human hair is 50 times wider) and 50 nm high,
meticulously carved out of silicon with an electron beam.

Each cluster contains dozens of posts, providing a formidable maze for
the molecules that are small enough to squeeze through them. And
molecules face a gauntlet of hundreds or even thousands of such
clusters, in a path only 10 microns wide (one-tenth the width of a
typical hair) and one cm long, folded into a serpentine path that fits
into one square millimeter on a silicon wafer -- a lab on a chip!

This system is a variation on the traditional size-exclusion
chromatograph, which consists of a column packed with a large number of
beads that have nano-scale pores. A liquid sample flows through the
beads, and the molecules sort themselves out according to how easily
they fit through the pores. A conventional benchtop SEC is about the
size of a large computer monitor.

By replacing the beads with nano-scale posts or channels, JPL is able to
make its version vastly smaller and much more controllable than its
larger predecessors. JPL hopes to fit the nano-SEC and all its
associated electronics into a package about the size of a paperback
book.

**The Microfluidic Ion Chromatograph**

The microfluidic ion chromatograph (micro-IC) is designed to analyze
small, inorganic ions in liquid samples. It sorts them by their
mobility, a measure of how rapidly an ion moves in solution under the
influence of an electric field.

The liquid flows by a series of electrodes in two interleaved comb
structures. An alternating electric field reverses the polarity of the
electrodes many thousands of times per second. When the electrodes carry
a negative charge, they attract the positively-charged ions (known as
cations).

An ion's mobility is determined by the ratio of its mass to its charge.
If two ions have the same charge, the larger one will move more
sluggishly, while the smaller one will be able to zip around more
nimbly. Some ions, however, carry a double charge. That increases their
attraction to the electrode, which can compensate for having to haul
more mass around. The higher the charge-to-mass ratio a molecule has,
the higher its mobility.

In the micro-IC, the high-mobility ions arrive at the nearest electrode
while the slower ions are still making their way. Imagine an 18-wheel
truck competing with a Ferrari for a parking spot across the street, and
you'll get the picture.

When an ion hits an electrode, its positive charge neutralizes the
negative electric field. No longer attracted, the lower-mobility ions
stop moving toward the electrodes and continue flowing downstream with
the liquid's current.

When the electrodes switch polarity, the high-mobility ions are released
and follow the low-mobility ions on their course down the stream. But
when, a fraction of a second later, the electrodes switch polarity
again, the faster-moving ions are once again drawn to them and the
process repeats.

The effect is that the higher the mobility of the ion, the more the
intermittent attraction of the electrodes interrupts its travels through
the chromatograph, and the longer it takes to complete the journey.
Conversely, the lower the mobility of the ion, the less it is diverted
by electrodes, and the faster it completes the trip. So in any given
sample, the results are similar to those of the SEC: the lowest-mobility
molecules (typically the largest) exit first, the highest-mobility
molecules (typically the smallest) exit last, and the intermediate
molecules exit in-between, in order of increasing charge-to-mass ratio.

Traditional ion chromatographs, which employ an ion-exchange procedure,
provide similar information. But while a state-of-the-art portable ion
chromatograph measures about 11 x 17 x 6 inches, JPL's micro-IC
separation column fits on a chip only 1 in. x 2 in. x 1 mm. The goal is
to miniaturize the whole system -- including valves, fluid reservoirs,
and control and measurement electronics -- to a handheld device
measuring about 1 x 2 x 3 inches.

**Applications**

Both types of liquid chromatograph systems are intended to monitor the
effectiveness of water purification systems on the International Space
Station and future manned spacecraft. They could also help to monitor
astronaut health with real-time analysis of bodily fluids such as blood,
saliva, and urine.

The nano-SEC provides a good way to separate high-molecular weight
molecules from chemically similar low-weight molecules -- for example,
proteins from amino acids and small peptides. And in addition to its
human health applications, it could serve in future missions to other
planets -- manned or robotic -- by looking for signs of life such as
small peptides and lipids.

When spacecraft carry hydroponic farms, like the systems described in
Life Support Modeling and Control, the micro-IC can help to monitor
nutrient solutions and keep them within the optimal range for plant
growth.