Mechanistic Challenges and Advantages of Biosensor Miniaturization into the Nanoscale

Over the past few decades, there has been tremendous interest in developing biosensing systems that combine high sensitivity and specificity with rapid sample-to-answer times, portability, low-cost operation, and ease-of-use. Miniaturizing the biosensor dimensions into the nanoscale has been identified as a strategy for addressing the functional requirements of point-of-care and wearable biosensors. However, it is important to consider that decreasing the critical dimensions of biosensing elements impacts the two most important performance metrics of biosensors: limit-of-detection and response time. Miniaturization into the nanoscale enhances signal-to-noise-ratio by increasing the signal density (signal/geometric surface area) and reducing background signals. However, there is a trade-off between the enhanced signal transduction efficiency and the longer time it takes to collect target analytes on sensor surfaces due to the increase in mass transport times. By carefully considering the signal transduction mechanisms and reaction-transport kinetics governing different classes of biosensors, it is possible to develop structure-level and device-level strategies for leveraging miniaturization toward creating biosensors that combine low limit-of-detection with rapid response times.