Design and Demonstration of Tunable Amplified Sensitivity of AlGaN/GaN High Electron Mobility Transistor (HEMT)-Based Biosensors in Human Serum.

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.

An integrated microfluidic system with field-effect-transistor sensor arrays for detecting multiple cardiovascular biomarkers from clinical samples.

Certain blood-borne biomarkers offer a potent methodology for understanding the risk of cardiovascular diseases (CVDs) with clinicians generally advocating the use of multiple biomarkers for proper risk assessment of CVDs. Herein four such CVDs biomarkers- C-reactive protein (CRP), N-terminal pro b-type natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI), and fibrinogen- were rapidly (5 min) analyzed from clinical samples (~ 4 µL) on an integrated microfluidic platform equipped with 1) immobilized highly specific aptamer probes and 2) field-effect transistor (FET)-based sensor arrays. The calibration curve from the FET sensor arrays showed good agreement in the physiological concentration ranges for CRP (0.1-50 mg/L), NT-proBNP (50-10,000 pg/mL), cTnI (1-10,000 pg/mL), and fibrinogen (0.1-5 mg/mL). The developed prototype of this fully automated portable device requires minimal reagent and sample inputs and consequently shows great promise for next-generation point-of-care devices assaying multiple CVDs biomarkers in clinical samples.

Risk stratification of heart failure from one drop of blood using hand-held biosensor for BNP detection.

Continued risk assessment by evaluating cardiac biomarkers in healthy and unhealthy individuals can lower the mortality rate of cardiovascular diseases (CVDs). In this research, we have developed a hand-held biosensor system to rapidly screen for brain natriuretic peptide (BNP) from a single drop of whole blood. The sensor methodology is based on extended gate design of electrical double layer (EDL) field effect transistor (FET), that can directly detect BNP in whole blood, without extensive sample pre-treatments, thereby eliminating the limitations of charge screening in high ionic strength solutions. A simple sensor array chip is fabricated to integrate with the MOSFET sensor system. Sensing characteristics are elucidated using purified BNP samples in 1 × PBS (with 4% BSA), spiked BNP samples in whole blood and clinical whole blood samples. The blood cells can be gravitationally separated without the use of any external actuation. The sensor exhibits very high sensitivity over wide dynamic range of detection. The sensing characteristics are not adversely affected by the presence of background proteins or blood cells, even without gravitational blood cell separation. Thus, the biosensor system can allow users to perform rapid whole blood diagnostics with minimal user protocols, in 5 min. The features of high sensitivity, cost-effectiveness and convenience of usage empower this technology to revolutionize the mobile diagnostics and healthcare industry.