We developed a new approach that utilizes the precise addressability of DNA nanotechnology constructs to allow quantitative biomolecule sensing with high sensitivity, specificity and reproducibility. Novel approaches to engineering DNA nanostructures allow the realization of tunable gain elements, in situ calibration of chemical concentration, and robust statistical sampling to enable biochemical measurement capabilities that far exceed state-of-the-art. The approach is compatible with common signal readout strategies (e.g., electronic, optical, etc.) and is chip scale. Implementations of the ideas described here will allow new applications in clinical diagnostics, therapeutic development, bionanotechnology and other applications.
The invention will allow precise colocalization of analyte-binding/signal-amplification motifs for easier characterization, as well as the ability to tune, for individual motifs, the binding affinity. This capability will greatly reduce the error rates of the measurements, allowing more robust results. This approach will greatly improve the long-standing problem of measurement specificity that has plagued applications in clinical diagnostics and other areas of healthcare. The nanoscale features of our new approach will also enable multiplexed measurements and rigorous sampling on chip to improve accuracy.