Two-Photon Nanolithography of Tailored Hollow three-dimensional Microdevices for Biosystems

[Image: see text] Functional three-dimensional (3D) microstructures incorporating accessible interiors have emerged as a versatile platform for biosystem applications. By configuring their 3D geometric features, these biosystem microdevices can accurately evaluate and control targeted bioenvironments. However, classical fabrication techniques based on photolithography-etching processes cannot precisely and programmably control the geometric of the entire hollow 3D microstructures. Here, we proposed the use of a two-photon polymerization (TPP)-based technique for the precise, straightforward, and customizable preparation of hollow 3D microstructure devices with small opening(s). Factors governing the formation of hollow 3D biosystem microdevices, including material composition, laser input, and (post-) development treatment, have been systematically investigated and a set of optimized conditions are presented as a starting point for the development of novel hollow biosystem microdevices. To evaluate the broad applicability of this approach, a series of tailored hollow 3D microdevices with small opening(s), including a micropore, microneedle, microelectrode, microvalve, and micromachine, were successfully prepared using our direct laser writing-TPP technique. To further validate the feasibility of these biosystem microdevices in practical implementations, we demonstrated the use of hollow 3D micropore devices for the robust resistive-pulse analysis of nanoparticles.