Calorimetry, a universal detection technology, measures directly the heat released or absorbed by chemical reactions. Despite their potential range of applications current microcalorimeters exhibit drawbacks that have precluded their use in the most current areas of biomedical research. These drawbacks derive from their relatively low sensitivity, requirement for large amounts of reactants and low throughput. Applications such as enzyme inhibition, screening for drug candidates, cell biology, proteomics, antibiotic profiling and clinical laboratory assays have been inaccessible to calorimetry. Recently, microelectromechanical MEMS-based microcalorimetric sensors and cells with extremely low volume (1uL) and high sensitivity (<1nW) have been developed and can be used to design and build a new generation of calorimeters that address unmet needs in biomedical research. The main goal of this SBIR is to develop a MEMS-based isothermal reaction calorimeter. MEMS devices (sensors and cells) will be fabricated and a prototype MEMS reaction calorimeter will be developed and characterized. The MEMS chip to be used in this research was developed at Columbia University and later licensed to Netzsch Instruments which will provide the sensor to AVIA Biosystems. AVIA Biosystems will design and develop a temperature control chamber (thermal enclosure, heaters and control electronics) specifically to accommodate the MEMS device. Fluidic, electrical control, data communication connections and data analysis software will be implemented for operation with a single MEMS chip. This approach will allow testing and optimization of each component. In Phase II an advanced multi-cell temperature controller capable of simultaneously processing 1-12 (or possibly up to 96) experiments will be developed for commercialization. The MEMS calorimeter will address critical areas that have not been amenable to calorimetric analysis with existing technologies. A MEMS instrument like the one proposed here will be capable of measuring changes in the rate of heat production after mixing two molecular or cellular components. Molecular systems can be enzyme/substrate system, ligand/receptor systems or more complex systems like cells, bacteria or other micro-organisms. This instrument will allow screening of drug candidates by measuring changes in the rate of heat production. This instrument will also find use in clinical laboratories as it allows accurate determination of enzyme or substrate concentrations without the need for optically clear samples or the use of cumbersome coupled reactions.
The device to be developed in this Phase 1 grant will advance and accelerate biomedical studies in which calorimetry can provide information previously unobtainable due to technology limitations. As such, it will have a tremendous impact in our understanding of biological processes and ultimately will contribute significantly to multiple medical fields.
