Nature has put one big obstacle between MIT’s Scott Manalis and his dream: the fact that living organisms — as opposed to, say, rocks — are, in terms of make-up, pretty moist.

Manalis wants to use an adapted version of a research tool called a resonant mass sensor to measure tiny amounts of various things, including proteins that may be signs of cancer.

If the proteins could be tested in a dry environment, this would be quite doable: you’d simply position your sample on your sensor’s vibrating platform and measure how it changed the frequency of the vibrations. In fact, such sensors are already used to measure astonishingly tiny entities. Even if a sample’s mass changes the platform’s vibrations by less than one part in ten million, Manalis notes, the sensor picks up that variation. “It’s incredible, when you think about it,” he says.

The system works because the sample is the only thing measured. But if your sample is in solution, you’ve got a problem.

Think of a springboard with someone perched on it. If you measured the frequency of the board’s movements before and after it’s occupied, you could get a reading on the person’s mass. But if the board happened to be mounted under water, the system would be of much less use. “You’d have the added effect of all that water, whose mass is so much greater than what you’re trying to measure,” explains Manalis, a professor of both mechanical and biological engineering.

Manalis felt that solving this problem would open the way for very fast and accurate measurements of biological targets. Longer term, he envisions chip-like devices that could, say, measure key proteins, or “biomarkers,” from a urine sample, and tell doctors whether the patient involved has cancer — and if so, exactly what type.

Is it feasible? In recent months, Manalis has surmounted key barriers to creating such devices.


Though Manalis’ Dad teaches environmental studies at the University of California, Santa Barbara — also Manalis junior’s alma mater — the future MIT faculty member had other interests. “What I was really drawn to was technology,” he notes.

So Manalis focused on physics both as an undergraduate and as a Stanford grad student, where his thesis was on tools to detect defects in integrated circuits. A summer stint at a biotech firm, though, made him recognize biology’s potential as an instigator of new technologies. “I got exposed to problems in biology, and what kind of technology might solve them,” he says.

Developing sensors to detect biological molecules emerged as one of his resulting interests. Why such a device? Most tests for entities like proteins — a class of molecules that includes hormones (estrogen) and enzymes (stomach acid) — involve “tagging” the protein with a fluorescing substance, which functions like the badges worn by some firms’ employees.

But the approach has its limits. For example, notes Manalis, “There are some proteins that are difficult to tag.” To create an alternative, though, he needed a way to overcome the sample-in-solution dilemma. His response was to create a sensor where, instead of trying to flow a fluid over the device’s vibrating part — the cantilever — you’d let it flow through that structure.

Here’s how it works: a machine pumps tiny quantities of, say, blood into a specially designed, finger-nail-sized silicon chip that has a series of vibrating cantilevers etched into it. Within the cantilevers, agents specifically chosen to grab hold of pre-selected proteins trap molecules of those proteins. A sophisticated monitor then reveals whether the target proteins are in that sample, and if so, in what quantities.

In recent attempts, Manalis has successfully measured test proteins in fluid environments along with larger targets like infectious bacteria. Longer term, he envisions commercialized versions that could lead to “the pregnancy test” — fast, cheap, and ultimately disposable — for many diseases, including cancer.

Aiding the struggle against ailments like cancer, Manalis admits, is a compelling prospect. But he adds that there’s a reason for the path he’s taken in pursuit of such goals. “What I get excited about,” he explains, “is making useful tools. And if a tool can be useful in an important way, that’s what I get most excited about.”