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Nanosensors for Medical Monitoring

Vista Therapeutics is developing ultra-sensitive detectors.

Physicians often test the levels of a few telltale blood proteins in seriously injured or ill patients to detect organ failure and other problems. Now Vista Therapeutics, a startup based in Santa Fe, NM, hopes to improve the care of these patients with sensitive devices for continuous bedside monitoring of such blood biomarkers. Instead of taking daily snapshots of the patient’s levels of blood proteins, the company’s nanosensors should allow for continuous monitoring of changes that occur over periods of only a few hours.

Warning signs: Vista Therapeutics is commercializing nanowire sensors for detecting early warnings of organ failure in trauma patients. Arrays of silicon nanowires like those on the chips above can detect individual proteins in unprocessed blood samples. The nanowires are labeled with antibodies, greenish-gray blobs in the chip image at right. The antibodies are also visible in the fluorescent images at left.

Spencer Farr, CEO of Vista Therapeutics, says that the first application of the technology will be for careful monitoring of patients whose status can change rapidly–such as those in the ICU after suffering a heart attack or traumatic injuries from a car accident. “We envision having a branch in the patient’s IV that tests continuously or every five to ten minutes,” says Farr. The nanowires are sensitive enough that they should be able to detect trace biomarkers that diffuse into the IV line from the blood. After a car wreck, for example, patients could be closely monitored for molecular warning signs of impending kidney and other organ failure.

To make the detectors, Vista Therapeutics has licensed nanowire sensing technologies developed by Harvard University chemist Charles Lieber. Silicon nanowires, semiconducting wires as thin as two nanometers, have what Lieber calls the “ultimate sensitivity,” even with completely unprocessed samples such as blood. When a single protein binds to an antibody along the wire, the current flowing through the wire changes. Arrays of hundreds of nanowires, each designed to detect a different molecule in the same sample, can be arranged on tiny, inexpensive chips. The changes can be monitored continuously as molecules bind and unbind, making it possible to detect subtle trends over time, without requiring multiple blood draws.

The standard protein-detection technique, ELISA, is very sensitive but, Farr says, takes 90 minutes to perform. It starts with a blood draw that must be extensively processed–first to purify the proteins, then to label them with fluorescent dyes–and then tested with expensive imaging equipment in a hospital lab. “ELISA is a powerful technology for one-time measurements,” says Farr, “but there’s no existing technology for continuous biomarker measurement.”

The sensitivity of nanowire detectors should also open up the possibility of finding new biomarkers. The blood biomarkers that doctors routinely test for–including prostate-specific antigen for cancer screening and c-reactive protein, a sign of heart failure–can be monitored with ELISA because their levels change over days or weeks. Because nanowire sensors allow for extremely sensitive, continuous monitoring, they should allow doctors to monitor the levels of blood proteins and other molecules whose concentration changes over a much shorter timescale. Changes in these biomarkers are currently undetectable. “We expect we’ll be able to include those that change rapidly, peaking within a matter of a few hours,” says Farr. Because it hasn’t been practical to make such measurements before, it’s not clear just what these biomarkers will be, but Farr hopes that Vista will uncover them.

Initially, Vista will market clinical devices for monitoring known biomarkers in IV lines. In the future, the company might develop implantable chips for patients with chronic diseases such as diabetes. A nanowire chip in an artery in the wrist might continuously monitor blood glucose and proteins indicative of early liver damage and other diabetic complications. The device could send alerts to a wristwatch. Because nanowires are so sensitive and inexpensive, they could also find their way into home tests for cancer, where early detection is key, says Farr.

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