"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.

1. 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.

2. 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.

3. 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!

Conventional benchtop size exclusion chromatograph, manufactured by Hewlett Packard.

Nanofabricated SEC will be an integrated handheld device, similar to the Sandia lab-on-a-chip shown above.

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.

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 Advanced System Modeling and Control of Bioregenerative Life Support, the micro-IC can help to monitor nutrient solutions and keep them within the optimal range for plant growth.