Addressing Signal Drift and Screening for Detection of Biomarkers with Carbon Nanotube Transistors.

Electrical biosensors, including transistor-based devices (i.e., BioFETs), have the potential to offer versatile biomarker detection in a simple, low-cost, scalable, and point-of-care manner. Semiconducting carbon nanotubes (CNTs) are among the most explored nanomaterial candidates for BioFETs due to their high electrical sensitivity and compatibility with diverse fabrication approaches. However, when operating in solutions at biologically relevant ionic strengths, CNT-based BioFETs suffer from debilitating levels of signal drift and charge screening, which are often unaccounted for or sidestepped (but not addressed) by testing in diluted solutions. In this work, we present an ultrasensitive CNT-based BioFET called the D4-TFT, an immunoassay with an electrical readout, which overcomes charge screening and drift-related limitations of BioFETs. In high ionic strength solution (1X PBS), the D4-TFT repeatedly and stably detects subfemtomolar biomarker concentrations in a point-of-care form factor by increasing the sensing distance in solution (Debye length) and mitigating signal drift effects. Debye length screening and biofouling effects are overcome using a poly(ethylene glycol)-like polymer brush interface (POEGMA) above the device into which antibodies are printed. Simultaneous testing of a control device having no antibodies printed over the CNT channel confirms successful detection of the target biomarker via an on-current shift caused by antibody sandwich formation. Drift in the target signal is mitigated by a combination of: (1) maximizing sensitivity by appropriate passivation alongside the polymer brush coating; (2) using a stable electrical testing configuration; and (3) enforcing a rigorous testing methodology that relies on infrequent DC sweeps rather than static or AC measurements. These improvements are realized in a relatively simple device using printed CNTs and antibodies for a low-cost, versatile platform for the ongoing pursuit of point-of-care BioFETs.

Fully printed prothrombin time sensor for point-of-care testing.

With an increasing number of patients relying on blood thinners to treat medical conditions, there is a rising need for rapid, low-cost, portable testing of blood coagulation time or prothrombin time (PT). Current methods for measuring PT require regular visits to outpatient clinics, which is cumbersome and time-consuming, decreasing patient quality of life. In this work, we developed a handheld point-of-care test (POCT) to measure PT using electrical transduction. Low-cost PT sensors were fully printed using an aerosol jet printer and conductive inks of Ag nanoparticles, Ag nanowires, and carbon nanotubes. Using benchtop control electronics to test this impedance-based biosensor, it was found that the capacitive nature of blood obscures the clotting response at frequencies below 10 kHz, leading to an optimized operating frequency of 15 kHz. When printed on polyimide, the PT sensor exhibited no variation in the measured clotting time, even when flexed to a 35 mm bend radius. In addition, consistent PT measurements for both chicken and human blood illustrate the versatility of these printed biosensors under disparate operating conditions, where chicken blood clots within 30 min and anticoagulated human blood clots within 20-100 s. Finally, a low-cost, handheld POCT was developed to measure PT for human blood, yielding 70% lower noise compared to measurement with a commercial potentiostat. This POCT with printed PT sensors has the potential to dramatically improve the quality of life for patients on blood thinners and, in the long term, could be incorporated into a fully flexible and wearable sensing platform.

Understanding and Mapping Sensitivity in MoS2 Field-Effect-Transistor-Based Sensors.

Sensors based on two-dimensional (2D) field-effect transistors (FETs) are extremely sensitive and can detect charged analytes with attomolar limits of detection (LOD). Despite some impressive LODs, the operating mechanisms and factors that determine the signal-to-noise ratio in 2D FET-based sensors remain poorly understood. These uncertainties, coupled with an expansive design space for sensor layout and analyte positioning, result in a field with many reported highlights but limited collective progress. Here, we provide insight into sensing mechanisms of 2D molybdenum disulfide (MoS2) FETs by realizing precise control over the position and charge of an analyte using a customized atomic force microscope (AFM), with the AFM tip acting as an analyte. The sensitivity of the MoS2 FET channel is revealed to be nonuniform, manifesting sensitive hotspots with locations that are stable over time. When the charge of the analyte is varied, an asymmetry is observed in the device drain-current response, with analytes acting to turn the device off leading to a 2.5× increase in the signal-to-noise ratio (SNR). We developed a numerical model, applicable to all FET-based charge-detection sensors, that confirms our experimental observation and suggests an underlying mechanism. Further, extensive characterization of a set of different MoS2 FETs under various analyte conditions, coupled with the numerical model, led to the identification of three distinct SNRs that peak with dependence on the layout and operating conditions used for a sensor. These findings reveal the important role of analyte position and coverage in determining the optimal operating bias conditions for maximal sensitivity in 2D FET-based sensors, which provides key insights for future sensor design and control.

Capping Layers to Improve the Electrical Stress Stability of MoS2 Transistors.

Two-dimensional (2D) materials offer exciting possibilities for numerous applications, including next-generation sensors and field-effect transistors (FETs). With their atomically thin form factor, it is evident that molecular activity at the interfaces of 2D materials can shape their electronic properties. Although much attention has focused on engineering the contact and dielectric interfaces in 2D material-based transistors to boost their drive current, less is understood about how to tune these interfaces to improve the long-term stability of devices. In this work, we evaluated molybdenum disulfide (MoS2) transistors under continuous electrical stress for periods lasting up to several days. During stress in ambient air, we observed temporary threshold voltage shifts that increased at higher gate voltages or longer stress durations, correlating to changes in interface trap states (ΔNit) of up to 1012 cm-2. By modifying the device to include either SU-8 or Al2O3 as an additional dielectric capping layer on top of the MoS2 channel, we were able to effectively reduce or even eliminate this unstable behavior. However, we found this encapsulating material must be selected carefully, as certain choices actually amplified instability or compromised device yield, as was the case for Al2O3, which reduced yield by 20% versus all other capping layers. Further refining these strategies to preserve stability in 2D devices will be crucial for their continued integration into future technologies.

Immunity to Contact Scaling in MoS2 Transistors Using in Situ Edge Contacts.

Atomically thin two-dimensional (2D) materials are promising candidates for sub-10 nm transistor channels due to their ultrathin body thickness, which results in strong electrostatic gate control. Properly scaling a transistor technology requires reducing both the channel length (distance from source to drain) and the contact length (distance that source and drain interface with semiconducting channel). Contact length scaling remains an unresolved epidemic for transistor scaling, affecting devices from all semiconductors-silicon to 2D materials. Here, we show that clean edge contacts to 2D MoS2 can provide immunity to the contact-scaling problem, with performance that is independent of contact length down to the 20 nm regime. Using a directional ion beam, in situ edge contacts of various metal-MoS2 interfaces are studied. Characterization of the intricate edge interface using cross-sectional electron microscopy reveals distinct morphological effects on the MoS2 depending on its thickness-from monolayer to few-layer films. The in situ edge contacts also exhibit an order of magnitude higher performance compared to the best-reported ex situ metal edge contacts. Our work provides experimental evidence for a solution to contact scaling in transistors, using 2D materials with clean edge contact interfaces, opening a new way of designing devices with 2D materials.

Electronic Stability of Carbon Nanotube Transistors Under Long-Term Bias Stress.

Thousands of reports have demonstrated the exceptional performance of sensors based on carbon nanotube (CNT) transistors, with promises of transformative impact. Yet, the effect of long-term bias stress on individual CNTs, critical for most sensing applications, has remained uncertain. Here, we report bias ranges under which CNT transistors can operate continuously for months or more without degradation. Using a custom characterization system, the impacts of defect formation and charge traps on the stability of CNT-based sensors under extended bias are determined. In addition to breakdown, which is well-known, we identify three additional operational modes: full stability, slow decay, and fast decay. We identify a current drift behavior that reduces dynamic range by over four orders of magnitude but is avoidable with appropriate sensing modalities. Identification of these stable operation modes and limits for nanotube-based sensors addresses concerns surrounding their development for a myriad of sensing applications.

High surface-area carbon microcantilevers.

Microscale porous carbon mechanical resonators were formed using carbon nanotube templated microfabrication. These cantilever resonators exhibited nanoscale porosity resulting in a high surface area to volume ratio which could enable sensitive analyte detection in air. These resonators were shown to be mechanically robust and the porosity could be controllably varied resulting in densities from 102 to 103 kg m-3, with pore diameters on the order of hundreds of nanometers. Cantilevers with lengths ranging from 500 µm to 5 mm were clamped in a fixture for mechanical resonance testing where quality factors from 102 to 103 were observed at atmospheric pressure in air.