Fabrication and electrical characterisation of an all-PMMA and PMMA/lipid bi-layer single submicron pore electrophoretic flow detector for biomedical applications

Abstract

► All-PMMA resistive pulse detector platform for eventual biomolecule identification. ► 450 nm pore diameter patterned by electron beam lithography in PMMA membrane. ► Alternatively, 1.5 nm self assembled protein pore in PMMA device. ► Detector system fabricated and electro-chemically characterized. ► Single stranded linear plasmid DNA molecules detected. We propose an eventually all-polymer flow detector platform based on PMMA membranes with single cylindrical pores covering two orders of magnitude (approximately 1.5 nm to 450 nm diameter) for the eventual identification of various biomolecules. Demonstrated rapid prototyping micropatterning sequences include electron beam lithography (EBL) and molecular self assembly (the latter to date depends on a PMMA/lipid bi-layer material sandwich), depending on desired pore sizes, and will get extended to X-ray lithography for parallel fabrication of proven layouts. In the case of 450 nm wide EBL patterned pores, long-term stability was proven over a period of 3 months and more, with an open pore current noise level determined in a patch-clamp setup to be better than 1%. Open pore current–voltage characteristics are linear and do scale with KCl electrolyte concentrations (0.1–0.75 M). The cylindrical pores do not exhibit rectification properties, as opposed to non-cylindrical pores (artificial or naturally occuring), and therefore allow for operation with either polarity. First test objects (synthesized silica nanospheres of 100 nm diameter) were detected as temporary current blockages of approximately 3.5%. Furthermore, self-assembled naturally occurring α-hemolysin pores of 1.5 nm diameter in a lipid bi-layer were introduced into the PMMA system to verify the detection of much smaller biomolecules, e.g. single stranded linear plasmid DNA. Current blockages of up to 10% were reproducibly detected.