Cleanroom-Free Toolkit for Patterning Submicron-Resolution Bioelectronics on Flexibles

Abstract

Fabricating flexible bioelectronics remains an ongoing challenge in pursuing a cost-effective, efficient, scalable, and environmentally friendly approach for research and commercial applications. The current dominant method, lithography, presents challenges due to its incompatibility with solvent-sensitive biomaterials and the phase mismatch between the photoresist and flexible substrates, such as elastomers. This study proposes a simplified, cleanroom-free toolkit as a potential alternative to lithography for fabricating intricate bioelectronics on flexible substrates with submicron resolution. This technique integrates a two-photon laser writing mask, mask transfer, and multi-layer/material patterning processes, enabling batch-to-batch processing and making it suitable for scalable production. With excellent conformal patterning capability, different functional and encapsulation biomaterials can be patterned on flexible substrates, including elastomers, parylene-C, polymer sheets, skin, fabric, and plant leaves. The versatility of this toolkit is validated by fabricating various prototypes of wearable and implantable bioelectronics, demonstrating excellent performance.

Keywords: flexible bioelectronics; submicron patterning; two‐photon laser.

Figure 1

Toolkit for integrating bioelectronics (see Figure S2 for examples, Supporting Information). The red scale bar is 3 µm, the black scale bar is 100 µm and the green scale bar is 5 mm.

Figure 2

a) Brain neuroelectrode array–device schematic with PDMS substrate, micron‐scale Pt electrodes, and PaC encapsulation layer; b) Real image of the fabricated electrodes integrated with FFC cable (scale bar: 5 mm); c) Comparison of biomaterials/substrate compatibility, fabrication simplicity, and cleanroom requirements between traditional lithography and our fabrication toolkit, specifically for fabricating this neuroelectrode array (see Table S1, Supporting Information for details); d) Electrode linewidth versus impedance (in vitro test, and the error bars represent measurements for three identical samples); e) in vivo experimental setup; f) Image and diagram of device employed as a penetrating probe for cortical recordings (scale bar: 3 mm); g) Raster plot of recordings obtained using device as a cortical penetrating probe, implanted into the sensory cortex of an anaesthetized rat; h) Sample traces recorded from cortical depth probe during skin brushing (grey box in (g), 400–2000 Hz); i) Image and diagram of device employed as an ECoG device on the brain surface (scale bar: 1.5 mm); j) Sample LFP traces recorded from ECoG device implanted on the cortex of an anaesthetized rat (10–300 Hz); k) Box plots of impedance values at 1 kHz for various device implanted into the brain. “L” denotes the large electrode device (300 µm diameter), and “S” denotes the small electrode device (140 µm diameter). n = 7 to 26 functional electrodes per device. Data shown in panels (g,h) and (j) are obtained from “L” (300 µm electrode diameter) devices. Colored electrodes in (f) and (i) represent electrode positions corresponding to the raster plot and traces in (g,h) and (j).

Figure 3

a) Electrical resistance changes with mechanical bending and stretching test; b) Fatigue buckling test under 50% of ∆L/L₀; c) Wrist pulse wearables–device schematic; d) Wrist pulse test results. The error bars represent measurements for three identical samples. Metal strip: 20 mm length × 100 µm width × 100 nm thickness.

Figure 4

a) Aptamer‐based biosensor mechanism, b) Characterization setup (blue–the methylene blue reporter, yellow–the aptamer base, red–the drug (doxorubicin), WE–working electrode, REF–the reference electrode Ag/AgCl, CE–the counter electrode Pt); c) Electrical signal recording with/without target drug; d) Signal change versus drug concentration. The error bars represent measurements for three identical samples.

Figure 5

a) OECT characterization setup (the gate electrode is Ag/AgCl; blue represents the PEDOT: PSS; grey indicates the Pt metal track; and there is a PaC encapsulation layer on top of the metal track); b–d) Characterization results of the fabricated OECT. The error bars represent an average from three measurements.