A Sensitive Electrochemical Biosensors Based on Glassy Carbon Electrodes Integrated with Smartphone for Prostate Cancer Detection

Abstract

Summary form only given. The complete presentation was not made available for publication as part of the conference proceedings. We present the development of a novel electrochemical biosensor for rapid and sensitive quantification of prostate specific antigen (PSA) in human serum samples. Carbon-Microelectromechanical Systems (C-MEMS) derived glassy carbon electrodes are the biosensors which are integrated with Smartphone based point-of-care diagnostic device for the detection. Additionally, a handheld potentiostat has been developed. This enables compact and reliable readout which is a critical element for field sensing. Prostate cancer turns out to be the second most common cancer and the sixth leading cause of cancer death among men, considering the global population. Laboratory based diagnostic tests using prostate serum antigen level detection are common practice and are routinely deployed for initial screening purposes. It is not trivial to employ those for early screening in resource limited settings. Despite the advancements in point-ofcare diagnostic devices towards addressing this challenging need, most of the reported methods in this regard either suffer from reduced minimum detection limits or scalability towards mass fabrication without compromising the costs incurred. Circumventing these constraints, we report here the development and validation of a sensitive, reliable, portable and affordable electrochemical biosensor. Carbon-MEMS technology is used to derive glassy carbon electrodes which are integrated uniquely with a Smartphone-based handheld potentiostat device for the estimation of the level of prostate serum antigen for point-of-care application. We accomplish this by developing glassy carbon electrodes using conventional carbon-microelectromechanical (C-MEMS) process, coupled with a handheld open-access mobile-interface potentiostat readout interfacing. SU-8 photoresist has been used as the carbon precursor. The carbon thin film electrodes have then been tested by cyclic voltammetry measurements in the potential range of −800 mV to +800 mV vs Ag/AgCl electrode in presence of 10 mM potassium ferrocyanide in 0.5 M potassium chloride solution. The presented device is the only label free analytical system for prostate cancer detection which requires simple operation to achieve a detection limit of 1 pg/ml in serum with a wide dynamic range up to 4 ng/ml. It also provides appreciable selectivity against potential interferents like horse radish peroxides (HRP) conjugated human immunoglobulin G(HRP-HIgG). Further, the developed device has been validated with commercially available existing systems using human serum samples and found satisfactory performance. Moreover, the proposed sensing system lowers the detection limit by three orders of magnitude compared to a recent study on label free point-of-care device on other cancer biomarkers (Table 1). We show schematic of the conversion of SU-8 electrode to carbon electrode in Figure 1(a). Here, two electrode pads of 3 mm × 3 mm area are connected through a 5 mm-long and 1 mm-wide strip. One pad is assigned for electrical connection and the other one for electrochemical sensing in bare condition or in functionalized state. SEM image of the carbon electrode taken at the corner of one pad is presented in Figure 1(b). Raman spectroscopy result of the fabricated bare carbon structures (pyrolyzed at 1000°C) is shown in Figure 1(c). This exhibits two dominant bands: disordered band (D-band) at around 1392 cm-1, and ordered band (G-band) at around 1607 cm-1 [1]. CV plots before and after 1 pg/ml PSA concentrations in serum has been represented in Figure 2(a). Figure 2(b) shows the variations of current sensitivities with different concentrations in buffer and serum after 1000 seconds. To summarize, the present electrochemical biosensor based on C-MEMS derived glassy carbon electrodes holds the advantages of affordability, convenient operability, mass production capability and portability along with high yield, significantly low detection limit compared to existing point-of-care testing devices, flexibility and specificity, thereby introducing them as new potential candidates for point-of-care testing of prostate cancer.