Detection Of Single Proteins Bound Along Dna With Solid-State Nanopores

Expression of genes in organisms is controlled through a number of mechanisms including epigenetic factors such as DNA-binding protein which cover cellular DNA at all times. Detection of these DNA bound protein is a challenge. Here we demonstrate, for the first time, that single DNA-bound proteins can be detected at the single-molecule level using solid-state nanopores. We show measurements that resolve single antibodies attached to DNA. We build on earlier work that demonstrated detection of small protein patches and show that single protein can be detected by increasing the measurement bandwidth while maintaining a good signal-to-noise ratio and addressing the stability of the DNA-protein complex in the high salt conditions required for measurement. We present experimental measurements carried out on several protein systems, discuss the current capabilities of this approach, and highlight several applications requiring single protein detection which are now feasible.