In Vitro Diagnostics

Advances in human genomics, bioinformatics, miniaturization and microelectronics and computer technology have lead to rapid growth in the market for in vitro diagnostic (IVD) equipment and tests. Currently, diagnostic testing accounts for only 1-2% of government healthcare expenditures worldwide, yet influences 60-70% of healthcare decisions.

ISurTec® currently is developing three technologies for the IVD market: 1) an improved surface chemistry for microparticles and nanoparticles used in specific binding assays such as genomic and proteomic arrays and flowing particle analyzer systems; 2) microparticle and “virtual well” microarray coatings for slides, plates and chips; and 3) a highly portable, lateral flow magnetic biosensor system based on Giant Magnetoresistive sensor chips.

Microparticles and Nanoparticles

Specific binding (e.g., antibody-antigen and hybridization) assays comprise a significant portion of current IVD testing. Many of these assays employ microparticles or nanoparticles modified with attached biomolecules. Despite widespread use, most microparticles or nanoparticles are not optimized for surface properties. Generally they have been developed for a particular size, shape, or property such as magnetism or fluorescence. Particle types include beads and fibers and can be comprised of biomaterials, synthetic polymers, inorganics and metals. Traditional microtiter plate assays are being replaced by particle-based assays using flow cytometry or derivatized optical fibers. The particles currently available have two inherent problems: one is that lot-to-lot consistency is low, requiring manufacturers to discard perhaps half the lots and forcing customers to spend time and money characterizing different lots; and the other problem is that the association between hydrophobic regions of the biomolecule and the particle surface can result in conformational changes and loss of biological activity.

ISurTec® is developing an improved surface chemistry for particles used in specific binding assays based on genomic and proteomic arrays as well as assays that employ flowing particle analyzers. Copolymers are being designed to bond photochemically to particle surfaces as well as bond to and stabilize desired biomolecules. These copolymers self assemble as single or stacked monolayers which passivate surfaces from non-specific protein absorbance and denaturation, and covalently bind biomolecules on tethers in a functionally “friendly” environment. These thin coatings maintain the size and shape of the particles being coated, as well as minimize the amount of coating required. Where thicker coatings may be advantageous, ISurTec is developing a multilayer technology.

Microarrays

Modern biology is following a path reminiscent of the early electronics industry; namely a miniaturization and large-scale integration process. This has revolutionized life science research, drug discovery and development, medical diagnostics, and biotechnology. Microarrays have become indispensable tools for life science research, showing scientists which genes are turned on or off in gene expression studies and shedding light on how large numbers of genes interact with one another. A microarray is an arrangement of miniaturized test sites or “spots” on a surface. Each spot is usually no more than 250 micrometers in diameter and contains biological molecules, typically DNA or protein, which act as probes for a test sample applied to the array. The surface may be a glass slide, a plastic plate with wells or a polymer bead. Microarrays are also components of biochips and lab-on-a-chip devices. This format allows many tests or experiments to be performed simultaneously leading to the generation of huge amounts of biological information from the application of only a tiny amount of sample.

Current microarray substrates do, however, include these deficiencies: 1) limitations in the printing of smaller and uniform spots of biomolecules, 2) background noise due to non-specific adsorption of signal-modulating components from the assay mixture, and 3) functional instability of biomolecules bound to the substrate. With optimization of the polymeric coatings placed on substrate surfaces, ISurTec® is working to correct each of these deficiencies.

Biosensors

Most remote water supplies are currently tested by commercial analytical laboratories which must grow cultures from the collected water samples, often taking days for identification and quantitative analysis. Other analytical options include immunofluorescence testing, followed by microscopic examination, which is labor intensive and time consuming. New sensitive methods such as RT-PCR, flow cytometry, and laser scanning are currently being developed. These are not yet commercially viable, however, and they require expensive laboratory equipment. In the field, there are few options for rapid analysis of water. Strip tests for some biocontaminants are commercially available, but they are typically limited to testing only 1-5 contaminants at a time and provide poor quantitation. An additional need would be an “at home test”, to look for disease markers, environmental contaminants, etc.

To address the issues described above, ISurTec® and its partners are developing a highly portable lateral flow magnetic biosensor system based on Giant Magnetoresistive sensor chips. We are focusing on surface modification chemistry to immobilize antibodies on device electrodes and magnetic particles while our partners are providing magnetic sensor chip and reader design, sensor and flow interface design, electrical design, and USB interface design. This biosensor will combine the sensitivity and accuracy of a biochip array with the ease of use and portability of a strip test. This “plug and play” system will allow literally anyone to collect a sample, place it on the assay strip, run the assay, and read the results via a USB port on a computer.

To learn more about any or all of three of these technologies and how they can be incorporated into your products, please CONTACT US.