A diagnostic "nanochip" that would detect markers of disease from all ovr the body

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TR: For the past several years, researchers at your institute have talked about a diagnostic "nanochip" that would detect markers of disease from all over the body. Can you update me on that project?

LH: What we're interested in doing is developing strategies that will let us identify proteins in the blood that will permit us to interrogate the state of individual organs: the liver, the heart, the muscle--whatever you'd like to look at.

The basic idea is that the organ-specific proteins from, say, the liver will reflect the operation of the networks in the liver. So they'll be at one set of concentrations for normal liver, and a different set of concentrations for a liver that has cancer or hepatitis or cirrhosis and other diseases. These blood fingerprints, then, are not assays for a disease; they're assays for all disease. We've looked at two organ systems: the brain and the liver. We've certainly verified in general ways these principles.

We'd like to be able to identify fiftyish organ-specific blood proteins from each of the organs, and then be able to measure them so we could have an organ-wide assay. We'd like to give you a very broad-spectrum screen of all the different major organs in disease. The challenge is to be able to do the measurements in the blood, because that's the only organ that's readily accessible; that's the only organ that bathes all other organs; and it's an organ whose fluid properties make it easily manipulable for measurement and so forth.

TR: What progress have you made?

LH: This is really a challenging project. We've been collaborating with James Heath at Caltech for about four years. We have a little nanochip, if you will, that can make 20 different measurements of blood proteins. It can make the measurements in about five minutes' time and is as sensitive as any assay out there right now. And it will probably operate across six to eight orders of magnitude [in terms of] concentration difference--that's really important if you want to make blood measurements, because a big organ like the liver puts a lot of proteins in the blood, and a small organ like the beta cells of the pancreas puts out very few. You have to be able to span many orders of magnitude if you're going to make appropriate measurements.

TR: When can we expect this nanochip?

LH: There are two challenges with the chip that we're currently facing. One, getting good antibody reagents is really difficult and really expensive. So we're going to explore alternative chemistries for creating protein-capture agents. The second big challenge for the nanochips is learning how to manufacture them on a scale that will make these measurements a few pennies per protein. The cost we have now is on the order of $50 per chip. And of course manufacturing is also important, to have good quality control, reproducibility in chip features. We're optimistic that both of those problems can be scaled and that we can scale chips up to make thousands of measurements.

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