Nano-Calorimetry based point of care biosensor for metabolic disease management

作者：Kazura Evan; Lubbers Brad R; Dawson Elliott; Phillips John A III; Baudenbacher Franz^*

来源：Biomedical Microdevices, 2017, 19(3): 50.

DOI：10.1007/s10544-017-0181-4

• Calorimetry
• Point of care
• Biosensor
• Thermopile
• Phenylketonuria
• Metabolic disease

Point of care (POC) diagnostics represents one of the fastest growing health care technology segments. Developments in microfabrication have led to the development of highly-sensitive nanocalorimeters ideal for directly measuring heat generated in POC biosensors. Here we present a novel nano-calorimeter-based biosensor design with differential sensing to eliminate commonmode noise and capillary microfluidic channels for sample delivery to the thermoelectric sensor. The calorimeter has a resolution of 1.4 +/- 0.2 nJ/(Hz) 1/2 utilizing a 27 junction bismuth/titanium thermopile, with a total Seebeck coefficient of 2160 mu V/K. Sample is wicked to the calorimeter through a capillary channel making it suitable for monitoring blood obtained through a finger prick (< 1 mu L sample required). We demonstrate device performance in a model assay using catalase, achieving a threshold for hydrogen peroxide quantification of 50 mu M. The potential for our device as a POC blood test for metabolic diseases is shown through the quantification of phenylalanine (Phe) in serum, an unmet necessary service in the management of Phenylketonuria (PKU). Pegylated phenylalanine ammonia-lyase (PEG-PAL) was utilized to react with Phe, but reliable detection was limited to < 5 mM due to low enzymatic activity. The POC biosensor concept can be multiplexed and adapted to a large number of metabolic diseases utilizing different immobilized enzymes.

• 出版日期2017-9