A MEMS-Based Isothermal Reaction Calorimeter for Biomedical Applications

DESCRIPTION provided by applicant 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 uL and high sensitivity andlt nW 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 or possibly up to 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 RELEVANCE The device to be developed in this Phase 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 PUBLIC HEALTH RELEVANCE The availability of a MEMS microelectromechanical calorimeter will provide a way to perform rigorous thermodynamic analysis in a variety of biomedical and pharmaceutical research areas The MEMS technology similar to what is used in all modern cell phones removes the greatest barriers to the expansion of the use of calorimetry in many fundamental and applied biomedical research fields This MEMS reaction calorimeter will find use in areas ranging from screening for novel pharmaceuticals to clinical laboratories as it allows accurate determination of the concentration of enzymes or substrates in different fluids