Fabrication and simulations of high-aspect-ratio nanopores for polymer-based resistive pulse sensors

Microfluidic devices are a class of Micro Electromechanical Systems (MEMS) intended for fluids manipulation, mostly liquids, in the order of microliters and below. The global market of micro and nanofluidic devices has experienced continuous growth over the past few years [1]. In 2020, this market was valued at over USD 4.6 billion in conservative terms, and it is predicted to keep a growth rate of somewhat between 13 and 23% in the next half-decade [2]–[3]. Microdevices are characterized by having at least one dimension in the micrometre range, as well as nanodevices, have it in the nanometer scale. The main applications to micro and nanofluidic devices are drug delivery, pharmaceutical and biotechnology research, clinical and point-of-care (POC) diagnostics [2]. Companies working in this field experienced a surge in demand with the rise of the COVID-19 pandemic. For the rapid testing against SARS-CoV-2, testing devices became necessary for screening populations afar from testing centers and health care facilities [4]–[5]. The development of micro-and nano detectors for new viruses is challenging even with all the background acquired from working with other viruses [6]–[7]. One long-standing detection approach was established in 1953 by W. Coulter for counting cells, a method which is known as Resistive Pulse Sensor (RPS) or Coulter counter [8]. In short, an RPS refers to two chambers filled with electrolyte solution and connected by a single orifice. The target delivered in one chamber shall flow through the orifice to the other chamber led by electrochemical forces. The translocation of the targets causes partial and non-permanent obstruction of the orifice. By monitoring the electric current during this assay, it induces the formation of a pulse-like shape representing a pulse of resistance. In the following decades, this method was adapted to the submicrometric scale with advances in micro-and nanofabrication techniques [9]–[10]. The fabrication of such micro detectors is often based on photolithography, but some emergent and alternative techniques are becoming more common [6, 11–12]. Focused ion beam (FIB) is one of these unconventional approaches that allow for patterning high aspect ratio structures into a mixture of materials [13]–[14]. A challenge to pattern composite materials (e.g., sandwich-like membranes), which might be based on polymers and metals, raises from the different physical properties of materials [15]. The sensitivity and applicability of RPS are directly dependant on the shape and quality of the final structure. For instance, wall smoothness is one of the parameters that should be considered when choosing a fabrication approach. In this work, we will present an advanced nanofabrication design based on focused ion beam technology to drill a nanopore into a polymer-metal-polymer membrane. The intricate structure to be presented in this work was chosen to avoid fabrication artifacts described previously [16]. Numerical simulations will be also provided for comparison with a trivial cylindrical design.