A Functional AM approach for Biofabricating Micro-Optofluidic Devices for Medical Non-invasive Diagnosis-related Bioapplications

Micro-optofluidic (MoF) devices, integrating microfluidics and optical sensing, offer significant advantages for medical diagnostics (Achille et al. 2021, Basiri et al. 2021, Bahmaee et al. 2020). They enable real-time, label-free detection with high sensitivity while requiring minimal sample volumes (Fiorini et al. 2005, Wu et al. 2023). Their potential for portable applications makes them promising tools for non-invasive disease monitoring across various medical fields. In this study, a MoF device was designed, fabricated, and characterized for potential medical non-invasive diagnostic applications. It was manufactured using a functional Additive Manufacturing (AM) approach to ensure suitable optical properties, surface chemistry, and biocompatibility. A biocompatible and transparent 3D-printable resin was selected, and the device was realized using the PSTL ultra-high-resolution 3D-printing technique. The primary function of the MoF device is two-phase flow process monitoring through optical detection based on optical absorption phenomenon (Cairone et al. 2016). Its performance was evaluated by studying slug-flow and cell concentration monitoring. The investigated slug-flow process was composed by air and water. Slug-flow monitoring is essential in several physiological and pathological conditions, including respiratory, cardiovascular, renal, and neurological medicine (Selsby et al. 1990, Leerson et al. 2023, Mohsen et al. 2021). For instance, in respiratory medicine, slug-flow monitoring aid in assessing mucus clearance in chronic obstructive pulmonary disease. In cardiovascular care, it helps detect emboli in dialysis and extracorporeal membrane oxygenation, while in intravenous therapy, it ensures precise drug infusion. The device was also tested for cell concentration monitoring by analyzing a two-phase mixture of Saccharomyces cerevisiae cells suspended PBS at different concentrations. Accurate cell concentration measurement is crucial for diagnosing various medical conditions (Laszlo et al. 2014, Hassan et al. 2015, Lehnert et al. 2024). In oncology, label-free MoF devices can detect circulating tumor cells (CTCs) in blood for early cancer detection. In hematology, they assist in determining red and white blood cell counts to diagnose anemia and infections. In nephrology they involve urine analysis to detect kidney diseases through cellular debris and infection markers. An extensive experimental campaign was conducted under various conditions, testing different laser power levels P∈{1;3;5} mW, flow rate FR∈{0.1;0.2;0.3} mL/min, and cell concentrations C∈{0;10^6;10^7;10^8 } in 10 mL of PBS. A Design of Experiments approach was used to determine optimal operating conditions for robust device performance. The results confirmed the MoF device's capability to effectively monitor slug-flow (R^2∈{76.94%;98.27%}) and differentiate between different cell concentrations (R^2=98.74%), demonstrating its potential for future medical diagnostics.