Handheld Nucleic Acid Analyzers For Clinical

Simultaneously with DoD-sponsored research, a number of private companies have pursued the development and fabrication of handheld nucleic acid analyzers with an eye toward capturing what is expected to be a very lucrative and burgeoning market in ''point-of-care'' (POC) diagnostics.

Convincing physicians and clinical laboratory directors that POC nucleic acid analyzers, much less molecular methods per se, are worth embracing has traditionally been difficult.[12] Sample processing, particularly of matrices with a high concentration of PCR inhibitors (such as blood), continues to be a major hurdle. Also, firms hoping to market POC diagnostics must convince physicians and laboratory directors that the sometimes higher costs of their assays can be justified by improved sensitivity and specificity over existing methods. Nonetheless, according to Small Times magazine author Marlene Bourne, currently 21 companies are working on molecular diagnostic devices involving analysis of nucleic acids; at least 12 appear to be interested in the POC market (''Bantamweights vs. giants: Is a lab-on-a-chip brawl a mismatch?,'' Small Times, October 31, 2003).

While an exhaustive recounting of these projects is beyond the scope of this entry, some of the more interesting platforms are worthy of mention.

Clinical Microsensors (CMS), a division of Motorola, was founded in 1995 to exploit technology, developed by researchers at the California Institute of Technology, for ''bioelectronic'' detection of nucleic acid hybridization events. In late 1998 CMS had produced a prototype handheld instrument, powered by a 9-V battery, that could accommodate a ''DNA chip'' fabricated to contain 14 gold electrodes with DNA probes attached to their surface. The device promised a degree of sensitivity sufficient to detect DNA in wastewater, sludge, and blood, all very challenging sample matrices.[13] In 2000 CMS unveiled a desktop instrument, the 4800 eSensorā„¢, which is now in commercial release; this can assay from 1 to 48 eSensor chips at one time. According to a December 2003 conversation with Motorola scientist Tim Tiemann, development of a handheld analyzer that would provide onboard sample processing and nucleic acid purification,

Fig. 4 Image of a prototype of Nanosphere's Verigene Mobile device, which will allow the user to perform sample processing and nucleic acid detection via hybridization assay in one handheld instrument suitable for the clinical diagnostic market. Inset: the company currently markets the portable Verigene ID system, which provides detection of nucleic acids via a proprietary, nanoparticle-mediated hybridization chemistry. (Photo courtesy of Jamie Abrams, Nanosphere, Northbrook, IL.) (View this art in color at www.dekker.com.)

Fig. 4 Image of a prototype of Nanosphere's Verigene Mobile device, which will allow the user to perform sample processing and nucleic acid detection via hybridization assay in one handheld instrument suitable for the clinical diagnostic market. Inset: the company currently markets the portable Verigene ID system, which provides detection of nucleic acids via a proprietary, nanoparticle-mediated hybridization chemistry. (Photo courtesy of Jamie Abrams, Nanosphere, Northbrook, IL.) (View this art in color at www.dekker.com.)

as well as incorporating eSensor-based detection technology, is actively ongoing.

One company has begun production (in June 2003) of a handheld nucleic acid analyzer suitable for use in a clinical diagnostic setting; this is the Verigeneā„¢ ID instrument (Fig. 4) which exploits the nanoparticle detection method developed in the laboratory of Chad Mirkin at Northwestern University, Illinois.[14] The initial Verigene ID assay is for detection of SNPs associated with coagulation disorders; future assays are planned for infectious agents and other clinical parameters.

Other firms developing POC diagnostic platforms based on array-mediated detection of nucleic acids include Nanogen, Affymetrix, and Caliper Technologies; all of which have experience in the fabrication of large, benchtop instruments. In addition to clinical tests, it is anticipated that handheld devices will also be useful for other situations in which molecular detection is particularly helpful, such as in monitoring crops and agricultural products for the presence of genetically modified organisms (GMOs); testing of environmental samples for the presence of viral, bacterial, fungal, and protozoal pathogens; and analysis of food for the presence of both pathogenic and spoilage-associated microorganisms.

For the devices mentioned above, the chemistry mediating detection of the nucleic acids of interest may or may not involve PCR and nucleic acid hybridization; for example, NuGen Technologies, Inc., (San Carlos, CA) is relying on a proprietary method called exponential single primer isothermal amplification which may allow for detection of very low quantities of target nucleic acids and can be adapted for use in microarray or microfluidic formats. Another interesting amplification chemistry is the loop-mediated isothermal amplification (LAMP), in which Bst DNA polymerase is used to mediate autocy-cling strand displacement DNA synthesis.[15]

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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