Hypersensitive Electrochemical Biosensors Based On Nanowell Array Structures For Point Of Care Technology PDF Download

As a result of numerous advances towards miniaturization in several diverse fields including chemistry, nanofabrication, microfluidics, and electronics, point-of-care (PoC) biosensors have become a promising tool to combat the most life-threatening and expensive health issues affecting the world today. PoC technology helps solve these problems by allowing for diagnostic tools typically restricted to centralized facilities to be brought closer to the point of diagnosis for faster and more frequent testing in both clinical and remote settings. While many biosensor types exist, electrochemical-based detection has the advantage that it is inherently compatible with circuits, requiring only electrodes for transduction, allowing it fully to benefit from both Moore's Law scaling and the well-established semiconductor manufacturing industry to produce miniaturized, cost-effective, and portable devices. However, there has been a lack of successful PoC electrochemical platforms capable of running multiple diagnostic tests or multi-analyte assays due to the difficultly of balancing power and area constraints of the circuitry with maintaining the required sensitivity. Therefore, in this dissertation, the circuit and system design of two electrochemical biosensor platforms are presented that explore the challenges of implementing both multi-technique and multi-analyte biosensors at the PoC. The first is a reconfigurable, multi-technique electrochemical biosensor designed for direct integration into smartphone technologies to enable personal health monitoring. By repurposing components from one mode to the next, the biosensor is able to efficiently reconfigure itself into three different measurement modes allowing it to run a variety of assays. Each distinct mode is able to match the performance of state-of-the-art single technique biosensors, while all being integrated onto a single device at a fraction of the size. The 3.9x1.65 cm2 module was used with a modular smartphone for a variety of real-world point-of-care applications. Scaling the sensors further for high-density multi-analyte testing, a 4,096-pixel electrochemical biosensor array in 180 nm CMOS is presented. It uses a coulostatic discharge sensing technique and interdigitated electrode (IDE) geometry design to reduce the size of the readout circuitry. Each biopixel contains an IDE with a 13 aA low-leakage readout circuit directly underneath. Compared to standard electrodes, the implemented IDEs along with their inherent 3-D trenches achieve an amplification factor of 10.5x from redox cycling. The array's sensor density is comparable to state-of-the-art arrays, all without augmenting the sensors with complex post-processing. The simultaneous detection of anti-Rubella and anti-Mumps antibodies in human serum is demonstrated.