Vladimir Kesler

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BEng, McGill University, 2016

MSEE, Stanford University, 2018

Email: vkesler@stanford.edu

CMOS-Integrated, Aptamer-based Bioelectronic Point-of-Care Diagnostics

Modern medical assays, used to determine biomolecular concentrations in patient samples, represent a powerful advance in patient care and diagnosis. However, these diagnostics remain limited by cost and accessibility. Most of these assays require multiple sample preparation steps conducted by trained personnel in a lab setting. Additionally, these assays use expensive reagents and instrumentation for the readout. In collaboration with the H. Tom Soh Laboratory, this project explores how CMOS technology can be leveraged to develop robust, inexpensive point-of-care molecular diagnostics.


Aptamer-based Sensors:

Conventional diagnostic assays rely on antibody-based affinity reagents to bind biomolecular targets. However, these reagents are costly to develop and manufacture and limited in scope of potential targets. Aptamers are an alternative type of affinity reagent, built of oligonucleotides that bind specifically to a target. These reagents are more versatile and can be developed for a wide variety of targets through many different selection schemes, such as SELEX or Particle Display[1]. Additionally, they can be manufactured cheaply without the use of cell culture.


Particle Display aptamer screening and evolution process [1]


BioFET

FET-based biomolecular sensors have been studied extensively, so as to find ways to leverage existing semiconductor manufacturing infrastructure to produce inexpensive molecular diagnostics. By detecting surface charge density changes, molecular binding events can be transduced into electrical signals[2].


BioFET [3,4]


However, these sensors are often limited by Debye screening in the analyte – an effect that limits the signal. Furthermore, the target molecule is often the source of the charge detected by the sensor. This project seeks to develop a universal, target-agnostic approach by combining novel aptamer-based sensing schemes with integrated electronics[3,4].

[1] Wang, J., Gong, Q., Maheshwari, N., Eisenstein, M., Arcila, M. L., Kosik, K. S., & Soh, H. T. (2014). Particle Display: A Quantitative Screening Method for Generating High-Affinity Aptamers. Angewandte Chemie International Edition, 53(19), 4796–4801. http://doi.org/10.1002/anie.201309334

[2] Kaisti, M. (2017). Detection principles of biological and chemical FET sensors. Biosensors and Bioelectronics, 98, 437–448. http://doi.org/10.1016/j.bios.2017.07.010

[3] Chen, T. T., Wen, C.-H., Huang, J.-C., Peng, Y.-C., Liu, S., Su, S.-H., … Chen, M. (2015). A semiconductor bio-electrical platform with addressable thermal control circuits for accelerated bioassay development. In Technical Digest - International Electron Devices Meeting, IEDM (Vol. 2015–Febru, p. 15.4.1--15.4.4). IEEE. http://doi.org/10.1109/IEDM.2014.7047058

[4] Huang, Y.J., Lin, C.C., Huang, J.C., Hsieh, C.H., Wen, C.H., Chen, T.T., Jeng, L.S., Yang, C.K., Yang, J.H., Tsui, F., Liu, Y.S., Liu, S., Chen, M., 2015. High performance dual- gate isfet with non-ideal effect reduction schemes in a soi-cmos bioelectrical soc. In: 2015
IEEE International Electron Devices Meeting (IEDM), pp. 29.2.1–29.2.4. http://dx.doi.org/10.1109/IEDM.2015.7409792.

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