Enhanced Biosensing Resolution with Foundry Fabricated Individually Addressable Dual-Gated ISFETs

Abstract

The adaptation of semiconductor technologies for biological applications may lead to a new era of inexpensive, sensitive, and portable diagnostics. At the core of these developing technologies is the ion-sensitive field-effect transistor (ISFET), a biochemical to electrical transducer with seamless integration to electronic systems. We present a novel structure for a true dual-gated ISFET that is fabricated with a silicon-on-insulator (SOI) complementary metal-oxide-semiconductor process by Taiwan Semiconductor Manufacturing Company (TSMC). In contrast to conventional SOI ISFETs, each transistor has an individually addressable back-gate and a gate oxide that is directly exposed to the solution. The elimination of the commonly used floating gate architecture reduces the chance of electrostatic discharge and increases the potential achievable transistor density. We show that when operated in a "dual-gate" mode, the transistor response can exhibit sensitivities to pH changes beyond the Nernst limit. This enhancement in sensitivity was shown to increase the sensor's signal-to-noise ratio, allowing the device to resolve smaller pH changes. An improved resolution can be used to enhance small signals and increase the sensor accuracy when monitoring small pH dynamics in biological reactions. As a proof of concept, we demonstrate that the amplified sensitivity and improved resolution result in a shorter detection time and a larger output signal of a loop-mediated isothermal DNA amplification reaction (LAMP) targeting a pathogenic bacteria gene, showing benefits of the new structure for biosensing applications.

Microfabricated Ion‐Selective Transistors with Fast and Super‐Nernstian Response

“…[ 16,46,47 ] However, dynamic (i.e., real‐time) responses have never been reported in the existing literature on the dual‐gated ISFETs. [ 45,48–52 ] The overall performance of the sensors reported here surpasses that of all transistor technologies, in particular, in terms of the current sensitivity and response time. Perhaps the most striking result we obtained here is that the current sensitivity depends on g m and hence can be easily increased by controlling g m through, for example, tuning of channel thickness.…”

Multi-Wire Tri-Gate Silicon Nanowires Reaching Milli-pH Unit Resolution in One Micron Square Footprint

“…In the field of bioanalytics, the large-scale integration of CMOS chips exposing arrays of liquid-gate FET pH-sensors has shown its potential in applications such as DNA sequencing [ 5 ], and holds the promise to innovate DNA quantification based on quantitative PCR [ 6 , 7 , 8 ]. If the paradigm of nanoscale multi-gate devices improved as well the SNR of liquid-gate sensors, it would be possible to reduce the sensor size and consequently increase the throughput of analytical systems.…”

Competing surface reactions limiting the performance of ion-sensitive field-effect transistors

“…[3,4] In particular, silicon nanowire FETs (SiNWFETs) have been used successfully for different sensing experiments. Although successful chemical sensing [5,6,7,8,9,10,11], label-free biosensing [12,3,13,4,14,15,16,17] and the recording of intracellular action potentials [18] have been demonstrated, the only commercial application is still pH sensing [3,19,20,21,22]. The reason for this development lies in the use of bare, high quality oxide surfaces such as Al 2 O 3 or HfO 2 which exhibit a high number of surface hydroxyl groups.…”