Pinhole Zero-Mode Waveguides

INV-15100

 

Zero-mode waveguides (ZMWs) are nanostructures that can be used to isolate and optically investigate single molecules using fluorescence measurements. ZMWs suffer from inefficiency problems with sample loading as they rely purely on diffusion for the localization of molecules in the ZMW detection volume. Several methods have been developed to counteract this inefficiency, including magnetic bead loading and the use of nanopores to electrophoretically draw in charged molecules. Unfortunately, magnetic bead loading does not yield exceptional improvements over diffusive loading. Nanopore ZMWs do produce orders of magnitude improvements in loading rates, but precise fabrication of single nanopores in large arrays of ZMWs requires electron beam drilling which is difficult, time-consuming, expensive, and not easily scalable, or helium ion beam drilling, which is slightly more scalable but does not currently offer the precision necessary.

 

Northeastern University researchers developed a method for efficient loading of large ZMW arrays that is easily scalable, faster, and cheaper than current methods. Using anisotropic etching techniques (i.e., reactive ion etching) or by deposition of non‑ideal thin films with defects can produce substrates with sub-nanometer scale pinholes. By fabricating ZMW arrays on to these substrates, creating large arrays of ZMWs with pinholes at the base of each well succeeds. By applying a voltage bias across the pinhole containing these substrates localizes molecules at the base of the ZMWs without the possibility of molecules translocating the membrane.

 

- Can achieve 6 orders of magnitude loading efficiency over existing techniques

- Has very low noise – can measure single fluorophores

- The process is scalable, faster, and cheaper

 

- Optical DNA sequencing

- It provides devices and methods useful for sequencing and characterizing single nucleic acid molecules

 

- License

- Partnering

- Research collaboration