Challenge #1 

 

Assay design and sample prep for low-abundance biomarkers of disease
 

Nanopores are digital counters–they can detect the presence of single copies of molecules and enable unprecedented early detection of disease. But how can you recognize your target in a messy sample like serum or saliva, especially when working with target concentrations in the femtomolar range? Assay design and covalent-binding sample prep chemistries are needed to enable the nanopore to recognize the needle in the haystack. 

​

Challenge #2 

​

Surface chemistry for pore lifetime improvement and molecular detection

Solid-state nanopores can digitally detect single copies of proteins, paving the way for early disease detection for things like cancer, Alzheimer's, and traumatic brain injury. But reliably detecting these proteins requires modifying the membrane and the walls of the pore with chemical moieties to enable non-stick coatings, to concentrate analytes near the pore, to slow down molecular translocation, or to provide chemical specificity to the nanopore sensor itself. 
 

Challenge #3

​

Wafer-scale fabrication of stable, low-noise, free-standing membranes

The sensitivity of a nanopore is dictated by its length, which is in turn dictated by the thickness of the supporting membrane, and its noise performance, which is dictated by the capacitance of the support structure and the surface chemistry of the membrane. The field needs chemically and electrically stable, low-capacitance, ultra-thin membranes approaching 2D thickness, with carefully controlled surface chemistry.

 

Challenge #4

 

Sequence-controlled polymer synthesis for molecular information storage
 

Humanity already produces data faster than we produce storage capacity, and the gap is growing exponentially. We need denser, stable storage media yesterday. DNA is nature’s hard drive, and the data density is off the charts compared to anything humans ever came up with. Synthetic analogs of DNA can be read by solid-state nanopores to answer this challenge, but methods to synthesize fully-synthetic sequence-controlled polymers at scale remain elusive.

​

Challenge #5

​

Drug discovery is more critical than ever, and the process is more expensive every time.

 

New workflows are needed, and single-molecule approaches can be part of the solutions. Solid-state nanopores can measure molecular interactions, complexification, and conformational changes, and techniques are needed to trap the molecule in the pore long enough to detect them reliably. 
 

Challenge #6

​

Enzyme linkage for molecular motion control

The translocation of molecules through solid-state nanopores is a transient thing. Technologies are needed to control the motion of molecules. The use of enzymes docked in or near the nanopore is a promising avenue of research toward this goal.
 

 

Challenge #7

​

Sample preparation for faster readout

A single nanopore detects targets at a rate of about 1 per second per nanomolar concentration. For targets in the pico- and femtomolar range, reasonable assay times require either large arrays of pores, or strategies to pre-concentrate target molecules (ideally both). We have the arrays covered. The field needs sample prep and microfluidics techniques to enhance the target concentration by 100-1000x prior to delivery to the nanopore.