An integrated circuit for chip-based analysis of enzyme kinetics and metabolite quantification

Cheah, B. C. , MacDonald, A. I., Martin, C., Streklas, A. J., Campbell, G., Al-Rawhani, M. A., Nemeth, B., Grant, J. P. , Barrett, M. P. and Cumming, D. R.S. (2016) An integrated circuit for chip-based analysis of enzyme kinetics and metabolite quantification. IEEE Transactions on Biomedical Circuits and Systems, 10(3), pp. 721-730. (doi:10.1109/TBCAS.2015.2487603) (PMID:26742138)

Cheah, B. C. , MacDonald, A. I., Martin, C., Streklas, A. J., Campbell, G., Al-Rawhani, M. A., Nemeth, B., Grant, J. P. , Barrett, M. P. and Cumming, D. R.S. (2016) An integrated circuit for chip-based analysis of enzyme kinetics and metabolite quantification. IEEE Transactions on Biomedical Circuits and Systems, 10(3), pp. 721-730. (doi:10.1109/TBCAS.2015.2487603) (PMID:26742138)

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Abstract

We have created a novel chip-based diagnostic tools based upon quantification of metabolites using enzymes specific for their chemical conversion. Using this device we show for the first time that a solid-state circuit can be used to measure enzyme kinetics and calculate the Michaelis-Menten constant. Substrate concentration dependency of enzyme reaction rates is central to this aim. Ion-sensitive field effect transistors (ISFET) are excellent transducers for biosensing applications that are reliant upon enzyme assays, especially since they can be fabricated using mainstream microelectronics technology to ensure low unit cost, mass-manufacture, scaling to make many sensors and straightforward miniaturisation for use in point-of-care devices. Here, we describe an integrated ISFET array comprising 216 sensors. The device was fabricated with a complementary metal oxide semiconductor (CMOS) process. Unlike traditional CMOS ISFET sensors that use the Si3N4 passivation of the foundry for ion detection, the device reported here was processed with a layer of Ta2O5 that increased the detection sensitivity to 45 mV/pH unit at the sensor readout. The drift was reduced to 0.8 mV/hour with a linear pH response between pH 2 – 12. A high-speed instrumentation system capable of acquiring nearly 500 fps was developed to stream out the data. The device was then used to measure glucose concentration through the activity of hexokinase in the range of 0.05 mM – 231 mM, encompassing glucose’s physiological range in blood. Localised and temporal enzyme kinetics of hexokinase was studied in detail. These results present a roadmap towards a viable personal metabolome machine.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Al-Rawhani, Dr Mohammed and Campbell, Mr Gordon and Grant, Dr James and Nemeth, Mr Balazs and Cumming, Professor David and MacDonald, Dr Alasdair and Barrett, Professor Michael and Cheah, Dr Boon Chong and Martin, Mr Christopher
Authors: Cheah, B. C., MacDonald, A. I., Martin, C., Streklas, A. J., Campbell, G., Al-Rawhani, M. A., Nemeth, B., Grant, J. P., Barrett, M. P., and Cumming, D. R.S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Science and Engineering > School of Engineering > Electronics and Nanoscale Engineering
Journal Name:IEEE Transactions on Biomedical Circuits and Systems
Publisher:IEEE
ISSN:1932-4545
ISSN (Online):1940-9990
Published Online:06 January 2016
Copyright Holders:Copyright © 2015 IEEE
First Published:First published in IEEE Transactions on Biomedical Circuits and Systems 10(3): 721-730
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher.
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
605821The Multi-Corder: Poly-Sensor TechnologyDavid CummingEngineering & Physical Sciences Research Council (EPSRC)EP/K021966/1ENG - ENGINEERING ELECTRONICS & NANO ENG
690421Glasgow Molecular Pathology (GMP) NodeKarin OienMedical Research Council (MRC)MR/N005813/1ICS - EXPERIMENTAL THERAPEUTICS