Label-free gold interdigitated microelectrodes immunosensor for prostate cancer biomarker

Prostate cancer is a slowly proliferating and non-symptomatic form of malignancy in the prostate gland. It is the second most commonly diagnosed type of cancer worldwide, with 28% deaths among diagnosed cases. Although with an introduction of cancer screening in the last few decades had saved countless lives, this technique could not reach out to the patients who live in rural areas due to its inherent complexities and non-portability. Recent developments in label-free and portable biosensing platforms using the gold-standard prostate-specific antigen are catered towards solving this current diagnoses loophole. Similarly, this research work develops a label-free gold interdigitated microelectrodes immunosensor which target to solve these limitations in the current cancer diagnostic technologies. In this work, an interdigitated microelectrodes architecture is chosen due to its superior detection sensitivity, portability and mass manufacturability. The device is fabricated in-house using an established Complementary Metal-Oxide Semiconductor fabrication process, with a gold microelectrode size of 10 μm and interdigitated gap size of 10 μm, integrated with a gold counter electrode and gold pseudo-reference electrode on a silicon dioxide substrate. For biosensing device development, two transducer surface modification schemes are demonstrated. Scheme 1 involves a self-assembled monolayer modification using amino-silanization of 3-aminopropyltriethoxysilane and immobilization of monoclonal antibody specific to prostate-specific antigen on the silicon dioxide substrate, meanwhile Scheme 2 involves modification of self-assembled monolayer using thiolation chemistry of 16-mercaptoundecanoic acid and immobilization of the monoclonal antibody on gold microelectrode surface. Successful sensor’s modification steps are validated using atomic force microscopy, water contact angle measurement, X-ray photoelectron microscopy, and cyclic voltammetry characterization techniques. The binding event of prostate-specific antigen target on device transducer is quantitatively measured using a highly-sensitive Electrochemical Impedance Spectroscopy technique in both Faradaic (in presence of redox species) and non-Faradaic (in absence of redox species) modes of measurement. The Faradaic measurement is performed by measuring the changes in charge transfer resistance in the electrochemical double layer upon target binding, meanwhile in non-Faradaic mode, the detection is made by measuring the changes in the double layer capacitance of the electrochemical system. Using the detection Scheme 1, the bio-detection of prostate-specific antigen in Faradaic mode reveals a linear detection range of 5000 ng/ml to 0.5 ng/ml, with a limit of detection at 0.377 ng/ml. On the other hand, in Scheme 2, Faradaic measurement reveals a linear detection range of 100 ng/ml to 0.01 ng/ml and limit of detection of 0.01 ng/ml. In non-Faradaic mode, linear detection range of 5000 ng/ml to 0.5 ng/ml and limit of detection of 0.5 ng/ml are reported. The sensors’ reproducibility, specificity and stability studies reveal highly promising sensing performances that warrant for future development into a point-of-care biosensing platform.