Detection of disease biomarkers from whole blood is very important in disease prevention and management. However, new generation assays like point-of-care or mobile diagnostics face a myriad of challenges in detecting proteins from whole blood. In this research, we have designed, fabricated, and characterized a portable biomedical sensor for the detection of cardiac troponin I (cTnI) directly from whole blood, without sample pretreatments. The sensing methodology is based on an extended gate electrical double layer (EDL) gated field effect transistor (FET) biosensor that can offer very high sensitivity, a wide dynamic range, and high selectivity to target analyte. The sensing methodology is not impeded by electrostatic screening and can be applied to all types of FET sensors. A portable biomedical system is designed to carry out the diagnostic assay in a very simple and rapid manner, that allows the user to screen for target protein from a single drop of blood, in 5 min. This biomedical sensor can be used in hospitals and homes alike, for early detection of cTnI which is a clinical marker for acute myocardial infarction. This sensing methodology could potentially revolutionize the modern health care industry.
In this study, a package technology has been developed for miniaturized filed-effect transistor (FET)-based biosensors. FETs were fabricated and diced as a 1 mm × 1 mm chip. The chip was then embedded in a plastic substrate and has a coplanar surface with that of the substrate. Photolithography followed by metal deposition and lift-off process was conducted to create metal lines, which connect the FET and extend to the edge of the plastic substrate. The FET-embedded plastic substrate was then engraved by laser to form a typical micro SD card and then passivated by photoresist, leaving the source-drain channel and the gate electrode open, followed by bonding a microfluidic channel made of PMMA. The packaged FET was tested in air and in buffer solution to confirm the well electrical isolation between metal interconnects and the solution, and the successful liquid flowing in the microfluidic channel. A FET sensor array was also made by embedding 8 FET chips into one plastic substrate with the same process. This package technology can largely reduce the cost of the sensor due to the very small size of the FET chip. The sensor chips can also be arbitrarily positioned into one plastic substrate to fit with multiple microfluidic channels, leading to great flexibility in the design of the sensor array. The result has shown a promising 2D system-in-package technology for sensor applications.
In this research, we have designed, fabricated and characterized an electrical double layer (EDL)-gated AlGaN/GaN high electron mobility transistor (HEMT) biosensor array to study the transmembrane potential changes of cells. The sensor array platform is designed to detect and count circulating tumor cells (CTCs) of colorectal cancer (CRC) and investigate cellular bioelectric signals. Using the EDL FET biosensor platform, cellular responses can be studied in physiological salt concentrations, thereby eliminating complex automation. Upon investigation, we discovered that our sensor response follows the transmembrane potential changes of captured cells. Our whole cell sensor platform can be used to monitor the dynamic changes in the membrane potential of cells. The effects of continuously changing electrolyte ion concentrations and ion channel blocking using cadmium are investigated. This methodology has the potential to be used as an electrophysiological probe for studying ion channel gating and the interaction of biomolecules in cells. The sensor can also be a point-of-care diagnostic tool for rapid screening of diseases.
We
have developed a swift and simplistic protein immunoassay using
aptamer functionalized AlGaN/GaN high electron mobility transistors
(HEMTs). The unique design of the sensor facilitates protein detection
in a physiological salt environment overcoming charge screening effects,
without requiring sample preprocessing. This study reports a tunable
and amplified sensitivity of solution-gated electric double layer
(EDL) HEMT-based biosensors, which demonstrates significantly enhanced
sensitivity by designing a smaller gap between the gate electrode
and the detection, and by operating at higher gate voltage. Sensitivity
is calculated by quantifying NT-proBNP, a clinical biomarker of heart
failure, in buffer and untreated human serum samples. The biosensor
depicts elevated sensitivity and high selectivity. Furthermore, detailed
investigation of the amplified sensitivity in an increased ionic strength
environment is conducted, and it is revealed that a high sensitivity
of 80.54 mV/decade protein concentration can be achieved, which is
much higher than that of previously reported FET biosensors. This
sensor technology demonstrates immense potential in developing surface
affinity sensors for clinical diagnostics.
In this research, we developed a miRNA sensor using an electrical double layer (EDL) gated field-effect transistor (FET)-based biosensor with enhanced sensitivity and stability. We conducted an in-depth investigation of the mechanisms that give rise to fluctuations in the electrical signal, affecting the stability and sensitivity of the miRNA sensor. Firstly, surface characteristics were studied by examining the metal electrodes deposited using different metal deposition techniques. The lower surface roughness of the gold electrode improved the electrical current stability. The temperature and viscosity of the sample solution were proven to affect the electrical stability, which was attributed to reducing the effect of Brownian motion. Therefore, by controlling the test conditions, such as temperature and sample viscosity, and the surface characteristics of the metal electrodes, we can enhance the stability of the sensor. Metal electrodes deposited via sputtering and e-beam evaporator yielded the lowest signal fluctuation. When ambient temperature was reduced to 3 °C, the sensor had better noise characteristics compared to room temperature testing. Higher viscosity of samples resulted in lower signal fluctuations. Lastly, surface functionalization was demonstrated to be a critical factor in enhancing the stability and sensitivity. MiRNA sensors with higher surface ratios of immobilized DNA probes performed with higher sensitivity and stability. This study reveals methods to improve the characteristics of EDL FET biosensors to facilitate practical implementation in clinical applications.
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