High-performance extended-gate ion-sensitive field-effect transistors with multi-gate structure for transparent, flexible, and wearable biosensors.

In this study, we developed a high-performance extended-gate ion-sensitive field-effect transistor (EG-ISFET) sensor on a flexible polyethylene naphthalate (PEN) substrate. The EG-ISFET sensor comprises a tin dioxide (SnO2) extended gate, which acts as a detector, and an amorphous indium-gallium-zinc-oxide (a-IGZO) thin-film transistor (TFT) for a transducer. In order to self-amplify the sensitivity of the pH sensors, we designed a uniquely-structured a-IGZO TFT transducer with a high-k engineered top gate insulator consisting of a silicon dioxide/tantalum pentoxide (SiO2/Ta2O5) stack, a floating layer under the channel, and a control gate coplanar with the channel. The SiO2/Ta2O5 stacked top gate insulator and in-plane control gate significantly contribute to capacitive coupling, enabling the amplification of sensitivity to be enlarged compared to conventional dual-gate transducers. For a pH sensing method suitable for EG-ISFET sensors, we propose an in-plane control gate (IG) sensing mode, instead of conventional single-gate (SG) or dual-gate (DG) sensing modes. As a result, a pH sensitivity of 2364 mV/pH was achieved at room temperature - this is significantly superior to the Nernstian limit (59.15 mV/pH at room temperature). In addition, we found that non-ideal behavior was improved in hysteresis and drift measurements. Therefore, the proposed transparent EGISFFET sensor with an IG sensing mode is expected to become a promising platform for flexible and wearable biosensing applications.

Ultrasensitive Coplanar Dual-Gate ISFETs for Point-of-Care Biomedical Applications.

The sensitivity of conventional ion-sensitive field-effect transistors (ISFETs) is limited by the Nernst equation, which is not sufficient for detecting weak biological signals. In this study, we propose a silicon-on-insulator-based coplanar dual-gate (Cop-DG) ISFET pH sensor, which exhibits better performance than the conventional ISFET pH sensor. The Cop-DG ISFETs employ a Cop-DG consisting of a control gate (CG) and a sensing gate (SG) with a common gate oxide and an electrically isolated floating gate (FG). As CG and SG are capacitively coupled to FG, both these gates can efficiently modulate the conductance of the FET channel. The advantage of the proposed sensor is its ability to amplify the sensitivity effectively according to the capacitive coupling ratio between FG and coplanar gates (SG and CG), which is determined by the area of SG and CG. We obtained the pH sensitivity of 304.12 mV/pH, which is significantly larger than that of the conventional ISFET sensor (59.15 mV/pH, at 25 °C). In addition, we measured the hysteresis and drift effects to ensure the stability and reliability of the sensor. Owing to its simple structure, cost-effectiveness, and excellent sensitivity and reliability, we believe that the Cop-DG ISFET sensor provides a promising point-of-care biomedical applications.

Quantitative Serodiagnosis of Scrub Typhus Using Surface-Enhanced Raman Scattering-Based Lateral Flow Assay Platforms.

A surface-enhanced Raman scattering-based lateral flow assay (SERS-LFA) technique has been developed for the rapid and accurate diagnosis of scrub typhus. Lateral flow kits for the detection of O. tsutsugamushi IgG (scrub typhus biomarker) were fabricated, and the calibration curve for various standard clinical sera concentrations were obtained by Raman measurements. The clinical sera titer values were determined by fitting the Raman data to the calibration curve. To assess the clinical feasibility of the proposed method, SERS-LFA assays were performed on 40 clinical samples. The results showed good agreement with those of the standard indirect immunofluorescence assay (IFA) method. SERS-LFA has many advantages over IFA including the less sample volume, simpler assay steps, shorter assay time, more systematic quantitative analysis, and longer assay lifetime. As SERS strips can be easily integrated with a miniaturized Raman spectrophotometer, field serodiagnosis is also more feasible.

Silicon-on-Insulator Double-Gate Ion-Sensitive Field-Effect Transistors Using Flexible Paper Substrate-Based Extended Gate for Cost-Effective Sensor Applications.

We developed ion-sensitive field effect transistors (ISFETs) with disposable paper extended gates (EGs). The sensing and the measuring part of conventional ISFETs are not separated and integrated on the same device. Therefore, if the sensing part is contaminated by reaction in a chemical solution, there is a problem that an expensive measuring part manufactured through a complicated process becomes also unusable. To overcome this problem and provide a cost-effective sensor platform, we constructed a high-sensitivity ISFET sensor with a measuring transistor part and a separate EG sensing part. In particular, in this experiment, a double-gate transistor capable of amplifying the sensitivity using the capacitive coupling effect between a top-gate and a bottom-gate, which differs from a general single gate transistor on an SOI substrate, was fabricated. As a result, the pH sensitivity of 1199.92 ± 32.4 mV/pH could be achieved using paper EG and dual-gate mode sensing operation, which greatly exceeds the theoretical Nernst limit (59.15 mV/pH at 25 °C) in single gate mode sensing operation. We also measured non-ideal effects such as the hysteresis and drift behavior of paper EGs, and demonstrated that they have excellent stability and reliability for long-term measurements. In addition, hysteresis and sensitivity were measured after 3, 7, 14 and 30 days to verify the aging effect of the continuous use of paper EGs. As a result, paper EGs showed stable operating characteristics for 30 days. Therefore, we expect that double-gate ISFETs with flexible paper EGs will have a significant impact on label-free, low-environmental impact, cost-effective, disposable, and flexible FET-based biosensor applications.

SERS-based droplet microfluidics for high-throughput gradient analysis.

In the last two decades, microfluidic technology has emerged as a highly efficient tool for the study of various chemical and biological reactions. Recently, we reported that high-throughput detection of various concentrations of a reagent is possible using a continuous gradient microfluidic channel combined with a surface-enhanced Raman scattering (SERS) detection platform. In this continuous flow regime, however, the deposition of nanoparticle aggregates on channel surfaces induces the "memory effect," affecting both sensitivity and reproducibility. To resolve this problem, a SERS-based gradient droplet system was developed. Herein, the serial dilution of a reagent was achieved in a stepwise manner using microfluidic concentration gradient generators. Then various concentrations of a reagent generated in different channels were simultaneously trapped into the tiny volume of droplets by injecting an oil mixture into the channel. Compared to the single-phase regime, this two-phase liquid/liquid segmented flow regime allows minimization of resident time distributions of reagents through localization of reagents in encapsulated droplets. Consequently, the sample stacking problem could be solved using this system because it greatly reduces the memory effect. We believe that this SERS-based gradient droplet system will be of significant utility in simultaneously monitoring chemical and biological reactions for various concentrations of a reagent.

Surface-enhanced Raman scattering aptasensor for ultrasensitive trace analysis of bisphenol A.

Surface-enhanced Raman scattering (SERS)-based aptasensor platform, using double strand DNA-embedded Au/Ag core-shell nanoparticles, has been developed for the ultrasensitive detection of bisphenol A (BPA) in water. By combining optimally controlled Au/Ag core-shell nanoparticles with the selective BPA binding characteristics of DNA aptamers, a highly sensitive limit of detection (LOD) of 10 fM could be achieved for BPA-spiked tap water over a wide concentration range from 100 nM to 10 fM. This LOD is two or three orders of magnitude lower than that reported for other BPA sensing techniques, and also yields a detection limit that is 100-1000 times lower than the US EPA-defined Predicted No Effect Concentration (PNEC) values in potable water. Total detection time is estimated to be about 40 min including the reaction between aptamer and BPA (30 min) and detection (10 min). This sensing platform is also suitable for field applications since measurement can be performed under aqueous colloidal conditions.