Early Detection of Lung Cancer Using High Electron Mobility Transistors

Lung cancer is the leading cause of cancer deaths in the world, among both men and women. It claims more lives each year than do colon, prostate, ovarian and breast cancers combined. Currently, diagnosis of lung cancer in stages I and II is very difficult and hence prognosis is delayed, leading to increased mortality rate. Carcinoembryonic antigen (CEA), is a common cancer biomarker and the expression of CEA above 5 ng/mL is suggestive of the presence of cancer. In this study, we utilize immunology, which is antibody/antigen reaction, with the combination of High Electron Mobility Transistor (HEMT) as the transducer, to develop a biosensor for detecting lung cancer biomarkers, electronically, as opposed to traditional ELISA techniques. HEMTs have already been demonstrated in gas, ion and biomolecule sensing purpose. When analytes accumulate on the gate area, the net charge on the HEMT surface changes. This electrical detection technique is simple, fast, and convenient. The detecting signal from the gate is amplified through the drain-source current, making the sensor very sensitive.

Figure 1 (a) and (b) show the schematic of AlGaN/GaN HEMT and the top-view of the device. To create a high quality HEMT device, a 3 μm-thick undoped GaN buffer layer and a 150 Å-thick undoped Al_0.25Ga_0.75N layer were deposited by metal-organic chemical vapor deposition (MOCVD) on the substrate. Mesa isolation was formed by Inductively Coupled Plasma (ICP) etching system for 28 seconds. Ti, Al, Ni and Au were deposited by Electron Beam Evaporation and were annealed at 850 °C for 45 seconds under N₂ flowing to form ohmic contacts. Passivation was provided by encapsulating the device with photoresist, with only the gate region open for antibody immobilization using photolithography.

After sensor fabrication, surface functionalization is carried out by thiol binding on gold. We mixed bi-functional thio-carboxylate with the CEA antibody and let the antibody bind with the carboxyl functional group by EDC-sulfo NHS coupling reaction. Then the device is incubated in this solution for 12 hours at 4 ºC. BSA is used for surface blocking and as a protein dilution buffer. For the sensor measurement, source-drain bias is fixed at 0.5 V and the current change induced by binding of CEA was measured by applying a 0.5 V gate voltage.

Figure 1 (c) shows the total charge accumulated for various concentrations of CEA. This can be used as an index to quantify the amount of CEA present in sample as it can distinguish various protein concentrations even in the physiological blood/serum concentration (1x PBS). The change in total charge with varying concentration of CEA can thus represent sensor calibration curve. Comparing to the conventional methods, the electronic detection of CEA using HEMT has the advantages of high sensitivity and low response time. We believe this method has the potential to further the research in the field of electronic biosensors.