On-CMOs microelectrode systems for enhanced isfet-based detection of DNA
File(s)
Author(s)
Keeble, Lewis
Type
Thesis
Abstract
Ion-sensitive field-effect transistors (ISFETs) can detect DNA via pH changes during amplification reactions, creating a complementary metal-oxide-semiconductor (CMOS)-based diagnostic platform that is portable, accessible, and accurate. Incorporating on-chip microelectrode systems has the potential to improve the speed and functionality of the device.
Firstly, by moving DNA towards the ISFET sensing array prior to amplification using electrokinetics, a reduced time-to-positive (ttp) is expected due to localised pH production. To estimate this effect, proton diffusion was modelled as part of novel monte-carlo first-passage and finite-element simulations. The monte-carlo simulation predicted a 96s reduction in ttp with all DNA trapped at the sensing surface rather than randomly distributed throughout the reaction solution.
To realise these anticipated improvements, on-CMOS interdigitated electrodes were fabricated through photolithography. These electrodes demonstrated the first electrokinetic DNA trapping on active CMOS. However, DNA trapping in amplification reaction solutions was not observed due to its high conductivity. Further CMOS integration was attempted by designing electrodes in the top-metal of a microchip, an approach that, whilst unsuccessful, guided further work.
Another role that on-CMOS electrodes can perform is providing the reference potential required for ISFET operation. For the first time, bond-pads of a commercial CMOS process were used as a base on which a fully electroplated Ag/AgCl quasi-reference electrode (QRE) was produced. This QRE demonstrated a drift rate of 0.3mV/hr, which is comparable to literature values, and promises better integration and scalability of the manufacturing process.
Finally, the ability of electrode systems to carry out sample preparation inspired a conceptual electrokinetic lab-on-CMOS diagnostic device. A microchip-based system comprising an array of 3D carbon electrodes on bond-pads, combined ISFET and impedance sensing, and CMOS-based $Ag/AgCl$ QREs was devised. This was supported by the first demonstration of electrokinetic DNA trapping using gold-plated bond-pads, thus achieving full CMOS-integration of a DNA trapping system.
Firstly, by moving DNA towards the ISFET sensing array prior to amplification using electrokinetics, a reduced time-to-positive (ttp) is expected due to localised pH production. To estimate this effect, proton diffusion was modelled as part of novel monte-carlo first-passage and finite-element simulations. The monte-carlo simulation predicted a 96s reduction in ttp with all DNA trapped at the sensing surface rather than randomly distributed throughout the reaction solution.
To realise these anticipated improvements, on-CMOS interdigitated electrodes were fabricated through photolithography. These electrodes demonstrated the first electrokinetic DNA trapping on active CMOS. However, DNA trapping in amplification reaction solutions was not observed due to its high conductivity. Further CMOS integration was attempted by designing electrodes in the top-metal of a microchip, an approach that, whilst unsuccessful, guided further work.
Another role that on-CMOS electrodes can perform is providing the reference potential required for ISFET operation. For the first time, bond-pads of a commercial CMOS process were used as a base on which a fully electroplated Ag/AgCl quasi-reference electrode (QRE) was produced. This QRE demonstrated a drift rate of 0.3mV/hr, which is comparable to literature values, and promises better integration and scalability of the manufacturing process.
Finally, the ability of electrode systems to carry out sample preparation inspired a conceptual electrokinetic lab-on-CMOS diagnostic device. A microchip-based system comprising an array of 3D carbon electrodes on bond-pads, combined ISFET and impedance sensing, and CMOS-based $Ag/AgCl$ QREs was devised. This was supported by the first demonstration of electrokinetic DNA trapping using gold-plated bond-pads, thus achieving full CMOS-integration of a DNA trapping system.
Version
Open Access
Date Issued
2023-03-15
Date Awarded
01/07/2023
License URL
Advisor
Georgiou, Pantelis
Rodriguez Manzano, Jesus
Sponsor
Engineering and Physical Sciences Research Council
Grant Number
EP/L016796/1
Publisher Department
Electrical and Electronic Engineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)