(Invited) BioFETs and Nanopore FETs: Nanoscale Silicon Field-Effect Transistors for Single-Molecule Sensing
Authors: Martens Koen , Barge David , Liu Lijun , Santermans Sybren , Delport Jacobus , Willems Kherim , Gevers Juliette , Du Bois Bert , Andrei Alexandru , Lagae Liesbet , Verhulst Anne , Ray Chaudhuri Ashesh , Severi Simone , Marion Sanjin , Van Dorpe Pol 
Published: September 2023

High read throughput single-molecule sensing is a cornerstone of established third generation long-read DNA sequencing technologies and is crucial for emerging protein sequencing technologies. These omics technologies are of great interest for essential understanding and applications in the life sciences. Field Effect Transistor (FET)-based single-molecule sensors promise advances in omics, by further enhancing read throughput with massive parallelization.

Here an overview is given of our recent progress on nanoscale bioFETs and nanopore FETs (NPFETs).

A bioFET is a FET gated by a liquid electrolyte rather than by a solid gate. The FET is turned into a biosensor by attaching probe biomolecules to the gate dielectric. These probes bind specifically to the target biomolecule of interest. The attachment of the targets to the probes on the gate dielectric surface shifts the FET threshold voltage.

A nanopore FET is an electrolytically gated FET as well, in which the gate gauges potential changes caused by a molecule moving, or translocating, through a nanopore, a nanoscale opening connecting two reservoirs. Nanopores have been firmly established as single-molecule sensors as the ionic current running through them is modulated by passing single molecules.

Nanoscale silicon bioFET sensors have single-molecule capabilities within their reach [1-4]. To realize single-molecule sensing the single-molecule signal-to-noise ratio (SNR) must be sufficiently high. Downscaling the device area is key to increase SNR (∝1/√area) [5]. Although many reported FET sensors have nanoscale cross-sections, their gate lengths are typically micron-scale. Our FET modeling work shows that a sufficiently large single-molecule Signal-to-Noise Ratio (SNR) can be obtained when nano-scaling all FET channel dimensions [6]. We have shown significant progress [1] toward single-molecule detection by fabricating and characterizing finFET sensors with a gate length of 50nm and have shown that Si FETs have the potential to enable single-molecule sensing.

Noise plays a central role in single-molecule sensing [7,8] and drift can also be a challenge in FET sensors [9]. Perhaps the greatest challenge for bioFETs is electrolyte screening which reduces the signal by masking the charge of target molecules with counterions. We have experimentally established the importance of non-linear screening, and the pH interference effect which can aggravate screening [10,11] and propose solutions.

The nanopore FET, senses single molecules translocating through the pore due to the so-called resistive divider effect [6]. The nanopore FET has been experimentally demonstrated as a single-molecule sensor in 2012 [12]. The nanopore FET’s device-level advantage is its potential high > 100 MHz bandwidth with sufficient signal-to-noise ratio (SNR). This has been studied theoretically [13] but is yet to be proven experimentally. The second, and most important advantage, is the superior integrability of nanopore-FETs into large-scale arrays.

In our recent simulation work making use of a dedicated nanofluidic nanodevice simulator we reveal that sensitivity can be boosted exponentially by increasing cis-trans bias [14].

We have fabricated and characterized a Nanopore-FET milestone device [15,16], which has a nanopore running through a nanoscale silicon FET channel, but without bottom reservoir (see Fig. 1). On this milestone device we obtain excellent electrolytically gated FET transfer and output characteristics demonstrating a low subthreshold swing of 67mV/decade, indicating excellent device quality.

Applications of the nanopore FET for omics and DNA data storage will be discussed.

FET-based sensing promises to strongly enhance the read throughput of single-molecule sensing by means of massive parallelization.

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Fig. 1. TEM cross-section of the NPFET milestone device.

[1] Santermans et al. IEEE International Electron Devices Meeting, 2020

[2] Li et al. ACS Nano 2017, 11, 12789−12795

[3] He et al. Angewandte Chemie, 55, 1, 2016

[4] Li et al. Nanoscale, 2016, 8, 16172

[5] Männik et al. Nano Letters, 8, 2008

[6] Santermans et al., to be published

[7] Martens et al. Int. Conf.
Noise Fluctuations (ICNF), 2019

[8] Bergfeld Mori et al. Solid-State Electronics 194, p. 108358, 2022

[9] Wuytens et al. IEEE Int. Reliability Physics Symposium, 2020

[10] Gupta, et al. IEEE Sensors Journal, 21, 4, p. 4143, 2020

[11] Santermans et al. ACS Sensors 6, 3, p. 1049, 2021

[12] Xie et al. Nature Nanotechnology, 7(2), pp.119-125, 2012

[13] Parkin and Drndić, ACS sensors, 3, 2, p. 313, 2018

[14] Verhulst et al., IEEE Sensors Journal, 22, 6, pp.5732-5742, 2022

[15] Liu et al., MNE, Leuven, Sep., 2022

[16] Martens et al. IEEE International Electron Devices Meeting, 2022

Figure 1