Universal Nanopore Platform Integrating Multiple Resistive Pulse Sensors into a Single Microfluidic Device

Abstract

Resistive pulse sensors have been used to characterise everything from whole cells to small molecules. Their integration into microfluidic devices have simplified sample handling whilst increasing throughput. Typically, these devices measure a limited size range or a specific analyte, making them prone to blockages in complex sample matrixes. To prolong their life and facilitate their use, samples are often filtered or prepared to match the sample with the sensor diameter. Here, we advance our tuneable flow resistive pulse sensor which utilises additively manufactured parts. The sensor allows parts to be easily changed, washed and cleaned, its simplicity and versatility allows components from existing nanopore fabrication techniques such as silicon nitride, polyurethane and glass pipettes to be integrated into a single device. This creates a multi-nanopore sensor that can simultaneously measure particles from 0.1 to 30 m in diameter. The orientation and controlled fluid flow in the device allows the sensors to be placed in series, whereby smaller particles can be measured in the presence of larger ones without the risk of being blocked. We demonstrate the device with a range of nanopore materials commonly found within the literature, the easiest to set up was the pulled glass pipette and glass nanopore membrane. However, the glass nanopore membrane was by far the most robust and reusable component tested. We illustrate the concept of a multi-pore flow resistive pulse sensor, by combining an additively manufactured tuneable sensor, termed sensor 1, with a fixed nanopore sensor, termed sensor 2. Sensor 1 measures particles 2 to 30 m in diameter, whilst sensor 2 can be used to characterise particles as small as 100 nm, depending upon its dimensions.

Multi-resistive pulse sensor microfluidic device

“…Within the literature, a range of materials have been tested for RPS applications, and some of the most common solid-state materials are SiN and SiO 2 . 43 In keeping with our philosophy to create an easy to fabricate and assemble device, we opted to first create pores using pulled glass capillaries. A pipette was mounted into the screw thread shown in Fig.…”

Localized Nanopore Fabrication via Controlled Breakdown

“…This liquid contact can also be introduced by a droplet using a pipette tip. Recently, Wang’s group demonstrated that the applied voltage can be controlled across different membranes and generate nanopores at a specific position in the flow system [ 155 , 156 , 197 ]. They also reported that CBD nanopores formed in a localized manner at the cross-disjoint mortise structures generated by Ga-FIB etching [ 198 ].…”