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Detecting and Monitoring Disease
Jamais Cascio, 19 Jul 05

cd4monitor.jpgIt's often tempting to think about the microchip revolution in terms of computers and communication devices, bits of machinery with functions obviously derived from their digital components. But microprocessors have had some of their most worldchanging effects in the realm of biomedicine, and not just in terms of faster computer sequencing of DNA. Two more examples of this have come up this week: one to monitor the progress of HIV infections, and the other to keep watch for pathogens of all types. Both will see the greatest use -- and greatest impact -- in the developing world.

The July 2005 issue of PLoS Medicine includes an article describing the development of a new tool for counting CD4 lymphocytes in the blood of people infected with HIV. CD4 count is a key measure for monitoring the progress (or stability) of HIV/AIDS, but the lack of inexpensive, easy-to-use equipment has hindered the ability of doctors in the developing world to keep an eye on the health of infected patients. Existing "flow cytometry" equipment is expensive and fragile, and even cheaper, more rugged versions still have reagent and training costs. The authors (from Massachusetts General Hospital, Harvard Medical School, Brigham and Women's Hospital, University of Texas, and Botswana-Harvard AIDS Institute Partnership) have developed and tested a prototype of a low-cost system based on "low-cost microfabrication, efficient light sources, and affordable microelectronics and digital imaging hardware" along with inexpensive "microfluidic" chips.

In tests, their cheap system performed as well as far more expensive flow cytometers. What's more, the design, with further refinement, could be made as a hand-held monitor:

With additional engineering of optics, electronics, and mechanical components along with advancements in integrated microfluidic systems, it should be possible to develop a point-of-care instrument that is battery-powered, uses simple light emitting diodes (LEDs), and secures analyzable digital images with affordable video imaging chips. When combined with an embedded microprocessor and disposable assay cartridges for both adult and pediatric monitoring manufactured from injection-molded plastic, it should be possible to create a functional CD4 counting device that can be used at the point of care.

Once refined, the system should provide a ten-fold reduction in cost of CD4 monitoring and dramatically reduce process complexity; it will make HIV health monitoring possible nearly anywhere. But even more exciting about this project is that the technology prototyped by the authors could have applications beyond the (very much needed) CD4 monitoring system:

We believe that the future of low-cost diagnostics for use in the developing world lies in the development of new lab-on-a-chip technologies that integrate sample preparation and sample measurement systems into miniaturized devices with minimal power requirements. [...] Although CD4 counting represents the most urgent need in HIV diagnostics for resource-poor settings, the microchip platform is adaptable to other important assays. Through the interface of the lymphocyte capture membrane described here with the previously reported microchip arrays, cellular assays like CD4 counts can be multiplexed with other molecular biomarker measurements (i.e., proteins and nucleic acids) on a single miniaturized chip. The rapid extension of the chip-based CD4 counting method described here to HIV RNA measurements, diagnostics for opportunistic infections, liver enzymes, and other biochemical markers of interest in infectious disease is feasible.

With AIDS still spreading rapidly in the developing world, inexpensive, easy-to-use health monitoring devices will be a necessary part -- along with inexpensive, widely-available medicines -- of an effective global response to the disease.

New Scientist reports on another low-cost, hand-held, microchip-based biomedical tool proposal. This one, from a team at Cornell University and Evergreen State College, is a biosensor device able to identify different strains of pathogens in 30 minutes (as opposed to the current average of 24 hours) and for just a few dollars in reagents. The biosensor functions in manner akin to a home pregnancy test. When a suspicious sample is heated up, cells break down, and genetic material is released; the sensor, impregnated with artificial cells matching the RNA from the target pathogens, is placed into the sample for a short period. If a red line appears, the pathogen is present.

Although manufacturers would have to create a wide assortment of pathogen-specific sensors, the process should still be far less expensive than most current biosensors, which rely on a time-consuming method called gene amplification.

“Instead of taking many hours and costing several hundred dollars to be carried out in a specialist lab, the new test should be fully portable – the size of a cellphone – and cost just a couple of dollars for a fast result,” says team member Antje Baeumner, associate professor of biological and environmental engineering at Cornell University.

“The idea is that it could be used directly in the field to sample meats and food products, or to test for diseases quickly and cheaply in cost-limited countries.”

The current test model is set up to check for four different strains of dengue fever virus. With further refinement, future biosensors should be able to check for a greater variety of pathogens in a single sample, and should work at even lower concentrations.

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