Guest Seminar - Proximity-Based DNA Nanotechnology with a Target-to-DNA Converter for High Signal Gain

Proximity-based DNA circuits have been designed for various biosensing applications due to their self-contained and autonomous characteristics. To enhance its performance in detecting biomarkers in minute quantity, we have investigated different molecular amplification schemes for signal amplification. DNA isothermal amplification techniques have been applied extensively for evaluating nucleic acid biomarkers but cannot be implemented directly on other types of biomolecules, such as proteins. Recently, we designed a proximity circuit that converts protein targets into DNA barcodes for isothermal DNA exponential amplification reaction, which we termed PEAR. The PEAR system was surprisingly more robust against non-specific DNA amplification, a common background generation phenomenon and is a major challenge faced in existing formats of the isothermal DNA amplification reaction. The as-designed PEAR exhibited good target responsiveness for protein detection with a dynamic range of 4 – 5 orders of magnitude and down to femtomolar target concentration. Overall, the PEAR molecular design has led to the development of a stable and robust configuration of DNA exponential amplification reaction to achieve high signal gain, and we foresee it as a promising enabler for ultrasensitive protein detection.