Large-scale production of polyimide micropore-based flow cells for detecting nano-sized particles in fluids

Abstract

In diagnostic and sequencing applications, solid-state nanopores hold significant promise as a single-molecule sensing platform. The fabrication of precisely sized pores has traditionally been challenging, laborious, expensive, and inefficient, which has limited its applications until recently. To overcome this problem, this paper proposes a novel, reliable, cost-effective, portable, mass-productive, robust, and ease-of-use micropore flow cell that works based on the resistive pulse sensor (RPS) technique in order to distinguish the different sizes of c nanoparticles. RPS is a robust and informative technique that can provide valuable details of the size, shape, charge, and individual particle concentrations in the media. By femtosecond laser drilling of a polyimide substrate as an alternate material, translocation of 100, 300, and 350 nm polystyrene nanoparticles in PBS buffer was distinguished by 0.1, 1, and 2 nA current blockade levels, respectively. This is the first time a micropore has been opened in a polyimide membrane using a femtosecond laser in a single step. The experimental and theoretical investigation, scanning electron microscopy and focused ion beam spectroscopy were performed to comprehensively explain the micropore's performance. We showed that our innovative micropore-based flow cell could distinguish nano-sized particles in fluids, and it can be used in large-scale production because of its simplicity and cost-effectiveness.

Fig. 1. Stack schematics view and real images of the flow cell. Schematic representation of (a) top PMMA element, (b) PI film including the two Ag electrodes, and (c) bottom PMMA element. (d) The schematic and real images of the fully assembled flow cell.

Fig. 2. (a) FIB image of single micropore in PI film drilled by femtosecond laser. (b) FIB cross-section of the hole (subsequent steps). (c, d and e) FIB cross-sections of different micropores.

Fig. 3. Conductance distribution of 25 micropores drilled by a femtosecond laser.

Fig. 4. Contact angle measurement of the bare PI membrane (a) and NaOCl treated for 2.5 minutes (b). The scale bar marks 1000 μm.

Fig. 5. I–V curves for PI micropore after 2.5 min (a) and 5 min (b) chlorination by NaOCl in PBS × 1 and buffered at pH 7.4.

Fig. 6. 300 nm PS nanoparticle translocations through a PI micropore (a) and dwell time vs. conductance blockade scatter plot for 300 nm PS nanoparticles (b) in +400 mV and −400 mV stimulus voltages.

Fig. 7. Various PS nanoparticle sizes translocations through a PI hole (a). Dwell time vs. conductance blockade scatter plot of 100, 300, and 350 nm PS nanoparticles (b).

Fig. 8. Focused ion beam images of the sidewall of micropore (a) before translocation and (b) after 100 nm PS particle translocations. The 100 nm PS particles stuck to the micropore side-wall after translocation are highlighted in a red circle.