Pores with Undulating Diameter for Multipronged Characterization of Single Particles and Cells in Resistive-Pulse Technique

Abstract

Single pores in resistive-pulse technique have been successfully used for the detection of cells, viruses, particles, and even molecules such as DNA and proteins. We have investigated application of pores with undulating opening diameter for the detection of particles and characterization of their physical and mechanical properties including size, shape and squishiness. The resistive pulses generated by polymer spheres passing through these pores had a repeatable pattern of large variations corresponding to these diameter changes. We showed that this pattern of variations enabled the unambiguous resolution of multiple particles simultaneously in the pore, that it could detect transient sticking of particles within the pore, and that it could confirm whether any individual particle completely translocated the pore. These results have practical importance for increasing the speed of resistive-pulse sensing, optimizing the detection of specific analytes, and identifying particle shapes. We also showed pores with undulating opening diameter developed local pressure drops, which were sufficiently large to probe mechanical properties of passing objects. Application to hydrogels as well as biological cells will be discussed.Methods to measure diffusion coefficient and electrokinetic velocity of individual particles will be discussed in context of performing detection from diluted solutions of an analyte. Balancing all forces acting on particles allowed us to observe random walk of individual particles in a pore and estimate their diffusion coefficient from the variance of diffusion velocities of a particle. Trapping of particles/cells for a controllable amount of time between few milliseconds and a few minutes will be presented as well.