Anran Gao

Enhanced Sensing of Nucleic Acids with Silicon Nanowire Field Effect Transistor Biosensors

Silicon nanowire (SiNW) field effect transistors (FETs) have emerged as powerful sensors for ultrasensitive, direct electrical readout, and label-free biological/chemical detection. The sensing mechanism of SiNW-FET can be understood in terms of the change in charge density at the SiNW surface after hybridization. So far, there have been limited systematic studies on fundamental factors related to device sensitivity to further make clear the overall effect on sensing sensitivity. Here, we present an analytical result for our triangle cross-section wire for predicting the sensitivity of nanowire surface-charge sensors. It was confirmed through sensing experiments that the back-gated SiNW-FET sensor had the highest percentage current response in the subthreshold regime and the sensor performance could be optimized in low buffer ionic strength and at moderate probe concentration. The optimized SiNW-FET nanosensor revealed ultrahigh sensitivity for rapid and reliable detection of target DNA with a detection limit of 0.1 fM and high specificity for single-nucleotide polymorphism discrimination. In our work, enhanced sensing of biological species by optimization of operating parameters and fundamental understanding for SiNW FET detection limit was obtained.

Signal-to-Noise Ratio Enhancement of Silicon Nanowires Biosensor with Rolling Circle Amplification

Herein, we describe a novel approach for rapid, label-free and specific DNA detection by applying rolling circle amplification (RCA) based on silicon nanowire field-effect transistor (SiNW-FET) for the first time. Highly responsive SiNWs were fabricated with a complementary metal oxide semiconductor (CMOS) compatible anisotropic self-stop etching technique which eliminated the need for hybrid method. The probe DNA was immobilized on the surface of SiNW, followed by sandwich hybridization with the perfectly matched target DNA and RCA primer that acted as a primer to hybridize the RCA template. The RCA reaction created a long single-stranded DNA (ssDNA) product and thus enhanced the electronic responses of SiNW significantly. The signal-to-noise ratio (SNR) as a figure-of-merit was analyzed to estimate the signal enhancement and possible detection limit. The nanosensor showed highly sensitive concentration-dependent conductance change in response to specific target DNA sequences. Because of the binding of an abundance of repeated sequences of RCA products, the SNR of >20 for 1 fM DNA detection was achieved, implying a detection floor of 50 aM. This RCA-based SiNW biosensor also discriminated perfectly matched target DNA from one-base mismatched DNA with high selectivity due to the substantially reduced nonspecific binding onto the SiNW surface through RCA. The combination of SiNW FET sensor with RCA will increase diagnostic capacity and the ability of laboratories to detect unexpected viruses, making it a potential tool for early diagnosis of gene-related diseases.

CMOS‐Compatible Silicon Nanowire Field‐Effect Transistors for Ultrasensitive and Label‐Free MicroRNAs Sensing

MicroRNAs (miRNAs) have been regarded as promising biomarkers for the diagnosis and prognosis of early-stage cancer as their expression levels are associated with different types of human cancers. However, it is a challenge to produce low-cost miRNA sensors, as well as retain a high sensitivity, both of which are essential factors that must be considered in fabricating nanoscale biosensors and in future biomedical applications. To address such challenges, we develop a complementary metal oxide semiconductor (CMOS)-compatible SiNW-FET biosensor fabricated by an anisotropic wet etching technology with self-limitation which provides a much lower manufacturing cost and an ultrahigh sensitivity. This nanosensor shows a rapid (< 1 minute) detection of miR-21 and miR-205, with a low limit of detection (LOD) of 1 zeptomole (ca. 600 copies), as well as an excellent discrimination for single-nucleotide mismatched sequences of tumor-associated miRNAs. To investigate its applicability in real settings, we have detected miRNAs in total RNA extracted from lung cancer cells as well as human serum samples using the nanosensors, which demonstrates their potential use in identifying clinical samples for early diagnosis of cancer.

Ultrasensitive Detection of Dual Cancer Biomarkers with Integrated CMOS-Compatible Nanowire Arrays

A direct, rapid, highly sensitive and specific biosensor for detection of cancer biomarkers is desirable in early diagnosis and prognosis of cancer. However, the existing methods of detecting cancer biomarkers suffer from poor sensitivity as well as the requirement of enzymatic labeling or nanoparticle conjugations. Here, we proposed a two-channel PDMS microfluidic integrated CMOS-compatible silicon nanowire (SiNW) field-effect transistor arrays with potentially single use for label-free and ultrasensitive electrical detection of cancer biomarkers. The integrated nanowire arrays showed not only ultrahigh sensitivity of cytokeratin 19 fragment (CYFRA21-1) and prostate specific antigen (PSA) with detection to at least 1 fg/mL in buffer solution but also highly selectivity of discrimination from other similar cancer biomarkers. In addition, this method was used to detect both CYFRA21-1 and PSA real samples as low as 10 fg/mL in undiluted human serums. With its excellent properties and miniaturization, the integrated SiNW-FET device opens up great opportunities for a point-of-care test (POCT) for quick screening and early diagnosis of cancer and other complex diseases.

Robust ultrasensitive tunneling-FET biosensor for point-of-care diagnostics

For point-of-care (POC) applications, robust, ultrasensitive, small, rapid, low-power, and low-cost sensors are highly desirable. Here, we present a novel biosensor based on a complementary metal oxide semiconductor (CMOS)-compatible silicon nanowire tunneling field-effect transistor (SiNW-TFET). They were fabricated “top-down” with a low-cost anisotropic self-stop etching technique. Notably, the SiNW-TFET device provided strong anti-interference capacity by applying the inherent ambipolarity via both pH and CYFRA21-1 sensing. This offered a more robust and portable general protocol. The specific label-free detection of CYFRA21-1 down to 0.5 fgml−1 or ~12.5 aM was achieved using a highly responsive SiNW-TFET device with a minimum sub-threshold slope (SS) of 37 mVdec−1. Furthermore, real-time measurements highlighted the ability to use clinically relevant samples such as serum. The developed high performance diagnostic system is expected to provide a generic platform for numerous POC applications.

Label-Free and Rapid Electrical Detection of hTSH with CMOS-Compatible Silicon Nanowire Transistor Arrays

Now a human thyroid stimulating hormone (hTSH) assay has been considered as a screening tool for thyroid disease. However, some existing methods employed for in-hospital diagnosis still suffer from labor-intensive experimental steps, and expensive instrumentation. It is of great significance to meet the ever growing demand for development of label-free, disposable, and low-cost productive hTSH detection biosensors. Herein, we demonstrate a novel sensing strategy for highly sensitive and selective immunodetection of hTSH by using a CMOS-compatible silicon nanowire field effect transistor (SiNW-FET) device. The SiNW chips were manufactured by a top-down approach, allowing for the possibility of low-cost and large-scale production. By using the antibody-functionalized SiNW-FET nanosensors, we performed the label-free and rapid electrical detection of hTSH without any nanoparticle conjugation or signal amplifications. The proposed SiNW biosensor could detect hTSH binding down to a concentration of at least 0.02 mIU/L (0.11 pM), which is more sensitive than other sensing techniques. We also investigated the influence of Debye screening with varied ionic strength on hTSH detection sensitivity, and real-time measurements on various concentrations of the diluted buffer. The simple, label-free, low-cost, and miniaturized SiNW-FET chip has a potential perspective in point-of-care diagnosis of thyroid disease.

Ultra-sensitive nucleic acids detection with electrical nanosensors based on CMOS-compatible silicon nanowire field-effect transistors

Silicon nanowire field-effect transistors (SiNW-FETs) have recently emerged as a type of powerful nanoelectronic biosensors due to their ultrahigh sensitivity, selectivity, label-free and real-time detection capabilities. Here, we present a protocol as well as guidelines for detecting DNA with complementary metal oxide semiconductor (CMOS) compatible SiNW-FET sensors. SiNWs with high surface-to-volume ratio and controllable sizes were fabricated with an anisotropic self-stop etching technique. Probe DNA molecules specific for the target DNA were covalently modified onto the surface of the SiNWs. The SiNW-FET nanosensors exhibited an ultrahigh sensitivity for detecting the target DNA as low as 1 fM and good selectivity for discrimination from one-base mismatched DNA.

Multiplexed detection of lung cancer biomarkers in patients serum with CMOS-compatible silicon nanowire arrays

In this work, a real-time assay for highly sensitive, label-free, multiplexed electrical detection of lung cancer biomarkers was developed by using silicon nanowire field-effect (SiNW-FET) devices. Highly responsive SiNW arrays were fabricated using a CMOS-compatible anisotropic self-stop etching technique with mass reproducibility and low cost character. The SiNW nanosensor was integrated with PDMS microfluidic device, which allows rapid analyte delivery, makes the analysis to be conducted using exceedingly small samples and enables potential multiplexed detection. The nanowire arrays allowed highly selective and sensitive multiplexed detection of microRNA (miRNA)-126 and CEA. Due to high surface-to-volume ratio that the nanowire dimensions confer, the detection floor of single molecule was achieved. The potential utility in identifying clinical samples for early diagnosis of cancer was demonstrated by analyzing biomarkers in clinical related samples. The developed nanosensor with capability for multiplexed real-time monitoring of biomarkers with high sensitivity and selectivity in clinically relevant samples is highly attractive for diagnosis and treatment of cancer and other diseases.

Thermocapillary Actuation of Droplets on a Microfluidic Chip

Abstract In this paper, we report a digital liquid transporting chip which can manipulate droplets precisely based on thermal Marangoni force induced by thermal gradient. Detailed mathematical discussion shows that threshold force for mobilization is a function of droplet size and liquid parameters, and droplet velocity after depinning is a function of applied thermal gradient, droplet size and liquid parameters. The device with Ti as micro-heater, Au film as pad, Cr/Au as controlling electrode arrays, high quality SiO2 film as dielectric layer on glass substrate is fabricated by silicon bulk process and employs fluorocarbon polymer as hydrophobic layer to functionalize the surface to be hydrophobic so as to facilitate droplet transportation. Test results show that transportation velocity of 3 μl DI water and silicone oil can reach 0.1 mm/s and 1 mm/s respectively at a voltage of 7 V. Driving voltage, transportation velocity of droplets and effect of contact angle hysteresis are discussed and the results are in agreement with theoretical results. The results provide some practical guidelines for the design of microfluidic chips based on thermocapillary actuation. In this study, we demonstrated that thermocapillary actuation of droplets is tunable and the chip can find great application in lab-on-a-chip due to its simple structure and low-cost fabrication process.

Electric double layer effect in a nano-scale SiO2 sacrificial layer etching process and its application in nanowire fabrication

Process controllability has become one of the key factors for utilizing micro-scale processes in nanofabrication. Sacrificial layer technology especially should be carefully handled to avoid excessive etching of nano-scale device structures. In this work, the etching behavior of a buffered HF (BHF) solution for thermally-grown silicon dioxide sacrificial layers with thicknesses in the range of 22 to 112.7 nm was characterized. For the first time, accelerated limiting of etching was reported for sub-50 nm layers. However, for thicker ones (more than 50 nm), almost constant rate isotropic etching was observed. A detailed discussion revealed that the conventional diffusion-induced etching model was no longer valid in such a minute structure, and the electric double layer (EDL) effect instead, was likely to dominate. Simulation was carried out to investigate the influence of the electric potential generated by an interfacial charge layer upon reactive ions in the etchant, which was proved to be consistent with the experimental results. By using such nano-scale sacrificial layer technology, combined with anisotropic silicon etching, cost-effective and stable production of silicon nanowires (SiNWs) was accomplished, with a uniform width down to 100 nm, respectively. Reliable electrical connection was also achieved by smooth transitions from the nanowire to single crystal silicon electrodes, which further confirmed the potential of this highly controllable process.