SBIR-STTR Award

Under the NIEHS SBIR, Biopraxis proposes to develop a high-throughput Doodlebug for screening large populations and large numbers of environmental samples for diverse chemical contaminants, including heavy metals, PCBs, pesticides, antibiotic residues, and naturally occurring toxins. Doodlebug is a new, reagentless biochip technology under development for the detection of (CBW) agents and explosives. Phase I will show that Doodlebug can detect low- molecular-weight contaminants; individually identify cross-reactive sample constituents; analyze inorganics and organics simultaneously; and detect these targets in complex real world samples, without any sample preparation or cleanup steps. Earlier studies have demonstrated the ability to specifically identify cross-reactive toxins and nitroaromatics, and have identified biomolecules that can be used to identify cross-reactive divalent metal cations; the methods developed on these studies will be adapted for use on the NIEHS program. By the end of Phase II, a simple, dipstick biochip will be incubated in a few microliters of sample, and then read out automatically, in seconds, using a unique "specific transducer." Because the transducer can analyze micron-sized biomolecule pixels, the biochips will be inexpensive, and because no reagents are required and samples can be very small, Doodlebug will be very economical. PROPOSED COMMERCIAL APPLICATION: NIESH is seeking new tools for screening large populations for exposure to inorganic and organic environmental agents. However, Doodlebug will have many other applications as well, including site characterization, wastewater monitoring, food and beverage analysis, and medical diagnostics. I.e., Doodlebug can be used to help prevent human exposure by helping to clean up existing pollution, preventing future pollution, and detecting contaminants in food products; and can be used to help diagnose illness due to exposure.

Biopraxis proposes to develop its platform mu/SERS TM technology as a high-throughput biochip for screening large populations and large numbers of environmental samples for diverse chemical contaminants, including heavy metals, PCBs, pesticides, antibiotic residues, and naturally occurring toxins. Unlike other biochips, ?SERS TM does not rely on the use of labels to tell when binding takes place. Instead, spectral fingerprints are collected directly from each pixel on the chip, using surface-enhanced Raman scattering (SERS) microscopy. Because these fingerprints contain a rich body of information on the chemistries of the biomolecule and any target bound to it, mu/SERS TM can not only tell whether binding took place, but can tell which targets were bound, produce information on how they were bound (i.e., the binding chemistries involved), and even tell whether the biomolecule could have bound its targets, or had become denatured. Phase l showed that mu/SERS TM can analyze inorganic and organic contaminants, simultaneously, and individually identify cross-reactive sample constituents in complex 'real world' samples, without sample preparation or clean-up steps. In addition, Phase l showed that the program can also lead to a biochip to screen for synergistic interactions between toxic compounds, in vitro, at the molecular level; and to the identification of biomarkers that reflect exposure to mixtures of inorganic and organic contaminants. On Phase l, fingerprints were collected from sub-attomole to low-zeptomole amounts of bound targets. Phase II is designed to optimize key parameters, in order to (a)predict the sensitivity that can be achieved in terms of the amount of sample and target concentration that will be needed; and (b)confirm that mu/SERS TM products will be economical and practical for high-throughput analyses. The studies will also lay the foundation for developing methods to fabricate compact, high-density biochips; explore a new method for producing high affinity biomolecules that can be used with any biomolecule-based assay or sensor; and develop a body of information on a potential mechanism for synergistic toxic interactions, and the factors that can affect it.

Thesaurus Terms:
Environmental Contamination, Environmental Toxicology, High Throughput Technology, Microarray Technology, Monitoring Device, Organic Chemical, Technology /Technique Development, Toxicant Screening Biomarker, Halobiphenyl /Halotriphenyl Compound, Heavy Metal, Pesticide, Toxin Raman Spectrometry, Biotechnology