Integration of 3D printed microlenses with vertically stacked photonic integrated circuits for biomedical applications

Analysis of extracellular vesicles (EVs) in blood samples is a key advancement of modern medicine allowing to diagnose conditions such as pancreatic cancer and cardiovascular disease. Photonic integrated circuits combined with 3D printed microlenses could be the heart of point-of-care medical devices optically detecting EVs as small as 150 nanometers in diameter. Within this paper we report on novel photonic device combining three photonic sensing methods: flow cytometry (FCM), fluorescence sensing and optical coherence tomography (OCT). The 3-in-1 multi-sensing platform is based on silicon nitride photonic integrated circuits (PIC), integrated with 3D printed microlenses as well as innovative photonic assembly techniques. Due to various operating wavelength ranges, the functions of FCM and fluorescence sensing (both 520 nm and 638 nm wavelengths) are combined on the same PIC, whereas the OCT functionality (750 nm–820 nm wavelength range) is realized on a separate PIC. After chip fabrication and lens 3D printing, both PICs get integrated through vertical stacking technique, resulting in enhanced device functionality and device miniaturization. Both PICs contain etched keyhole-shaped slots allowing for physical insertion and real-time active alignment of a medical glass capillary in their center. The transmitted and detected optical signals are propagating through free space (air). Microlenses get 3D printed on the internal circumference of the keyhole-shaped slots, focusing the light from the waveguides onto the glass capillary and collecting the scattered optical signal after its interaction with the biological sample. The additive manufacturing printing process combines two-photon polymerization with lithographic-level alignment technology. We report to have enabled high-precision printing of 3D microstructures with feature sizes down to 100 nanometers and optical-grade surface quality as well as their integration with vertically stacked photonic integrated circuits for biomedical applications such as FCM, fluorescence sensing and OCT.