Extended-gate field-effect transistor packed in micro channel for glucose, urea and protein biomarker detection.

This study developed a packaging method to integrate the extended-gate field-effect transistor (EGFET) into a microfluidic chip as a biological sensor. In addition, we present two immobilization approaches for the bio-recognition that are appropriate to this chip, allowing it to measure the concentrations of hydrogen ions, glucose, urea, and specific proteins in a solution. Alginate-calcium microcubes were used to embed the enzymes and magnetic powder (enzyme carrier). When the sensing chip needs the enzyme for the catalytic reaction, the alginate microcubes containing the corresponding enzymes enter through the flow channel and are immobilized on the EGFET surface with an external magnet. High sensing performance of the chip is achieved, with 37.45 mV/mM for measuring hydrogen ions at pH 6-8 with a linearity of 0.9939, 7.00 mV/mM for measuring glucose with a linearity of 0.9962, and 8.01 mV/mM for measuring urea with a linearity of 0.9809. In addition, based on the principle of the immunoassay, the magnetic beads with the specific antibody were used to capture the target protein in the sample. Then, negatively charged DNA fragments bound to a secondary antibody were used to amplify the signal for EGFET measurement. The magnetic beads with completed immune response bonding were then fixed on the surface of the sensor by an external magnetic field. Therefore, the measured object can directly contact the sensor surface, and quantitative detection of the protein concentration can be achieved. Apolipoprotein A1 (APOA1) was detected as a target protein, with a minimum detection limit of approximately 12.5 ng/mL.

Optical sensing of urinary melatonin with molecularly imprinted poly(ethylene-co-vinyl alcohol) coated zinc oxide nanorod arrays.

In this work, aligned zinc oxide (ZnO) nanorods were selectively hydrothermally grown on acetate-seeded spots on a gold substrate; the nanorods had an average length and diameter of 1.7µm and 240nm, respectively. Melatonin was imprinted into poly(ethylene-co-vinyl alcohol), EVAL, which was coated onto ZnO nanorod arrays. The ZnO nanorods not only increased the surface area for sensing target molecules, but also constituted an optical sensing element, as the ZnO fluorescence decreases when targets bind to the imprinted EVAL film; the fluorescence decrease, as a function of melatonin concentration, is well fit by a Langmuir adsorption isotherm. Poly(ethylene-co-vinyl alcohol) with 44mol% ethylene showed the best imprinting effectiveness (ratio of the fluorescence decrease on binding melatonin to imprinted vs. non-imprinted EVAL-coated ZnO nanorod arrays) among the several compositions studied. In real urine analysis, the MIP films responded linearly to added (exogenous) melatonin, even in the presence of many possible interfering compounds in urine. This demonstrates the feasibility of using these MIPs as part of a total urinalysis MIP system.

A micro-cantilever sensor chip based on contact angle analysis for a label-free troponin I immunoassay.

Cantilever sensors have been extensively explored as a promising technique for real-time and label-free analyses in biological systems. A major sensing principle utilized by state-of-the-art cantilever sensors is based on analyte-induced surface stress changes, which result in static bending of a cantilever. The sensor performance, however, suffers from the intrinsically small change in surface stress induced by analytes, especially for molecular recognition such as antigen-antibody binding. Through the contact angle change on a tailored solid surface, it is possible to convert a tiny surface stress into a capillary force-a much larger physical quantity needed for a practical sensor application. In this work, a micro-cantilever sensor based on contact angle analysis (CAMCS) was proposed to effectively enhance the sensitivity of a sensor in proportion to the square of the length to thickness ratio of the cantilever structure. CAMCS chips were fabricated using a standard complementary-metal-oxide-semiconductor (CMOS) process to demonstrate a 1250-fold enhancement in the sensitivity of surface stress to bioanalyte adsorption using a piezoresistive sensing method. A real-time and label-free troponin I (cTnI) immunoassay, which is now widely used in clinics and considered a gold standard for the early diagnosis and prognosis of cardiovascular disease, was performed to demonstrate cTnI detection levels as low as 1 pg mL(-1). The short detection time of this assay was within several minutes, which matches the detection time of commercially available instruments that are based on fluorescence-labeling techniques.

A CMOS cantilever-based label-free DNA SoC with improved sensitivity for hepatitis B virus detection.

This paper presents a highly-integrated DNA detection SoC, where several kinds of cantilever DNA sensors, a readout circuit, an MCU, voltage regulators, and a wireless transceiver, are integrated monolithically in a 0.35 µm CMOS Bio-MEMS process. The cantilever-based biosensors with embedded piezoresistors aim to transduce DNA hybridization into resistance variation without cumbersome labeling process. To improve detection sensitivity for low DNA concentration use, an oscillator-based self-calibrated readout circuit with high precision is proposed to convert small resistance variation ( of original resistance) of the sensor into adequate frequency variation and further into digital data. Moreover, its wireless capacity enables isolation of the sample solution from electrical wire lines and facilitates data transmission. To demonstrate the effectiveness of full system, it is applied to detect hepatitis B virus (HBV) DNA. The experimental results show that it has the capability to distinguish between one base-pair (1-bp) mismatch DNAs and match DNAs and achieves a limit of detection (LOD) of less than 1 pM.