Microphysiological systems (MPS) are advanced in vitro platforms engineered to replicate in vivo conditions for studying human biology, disease mechanisms, and drug responses with greater physiological relevance. Fluorescence sensing is widely used as a functional readout in MPS due to its high sensitivity, selectivity, and stability. However, conventional fluorescence sensing systems often rely on bulky instrumentation with limited integration, which restricts continuous in situ monitoring, scalable high-throughput analysis, and spatially resolved investigation in multi-organ-on-a-chip models. To address these limitations, we present a highly miniaturized, fully integrated optical system with a 1 mm² footprint, enabling continuous in situ fluorescence monitoring of three-dimensional microtissues in close proximity. The system integrates microscale illumination and sensing units for fluorescence excitation and selective detection, an optical element for guided light propagation, and a microcage for mechanical confinement of microtissues. To demonstrate its capabilities, we integrated the miniaturized optical system with an MPS-relevant platform to monitor fluorescence signals in transgenic mouse pancreatic islets expressing genetically encoded calcium indicators. The integrated platform enables real-time, continuous monitoring of islet responses to potassium chloride stimulation and tracking of calcium oscillations for over two hours, providing valuable information about the functional status of the pancreatic islets. Our work enhances the analytical capabilities of MPS through the integration of miniaturized on-chip quantitative assessment tools, enabling precise, in situ, and continuous monitoring of biological activities in close proximity.

In vivo fluorescence sensing devices have recently gained considerable attention owing to their capabilities and potential in advancing biomedical research, clinical diagnostics, and therapeutic applications. In this work, we present a highly miniaturized, fully implantable device capable of excitation, detection, and recording of fluorescence signals, enabling continuous measurements of biological processes in vivo. The device was engineered to be minimally invasive, with a compact 5×5×5mm³ form factor. It incorporates an optical system integrating micro illumination and sensing units with a sub-mm2 footprint, achieving selective detection of fluorescence signals in close proximity. Additionally, the device features low-power on-board electronics and a customized bi-stable magnetic switch for remote activation, resulting in a device lifetime of over a month once the device is powered on. The device successfully recorded the infusion of green fluorescence protein (GFP) solution at a low concentration of 100 μg/mL delivered at a rate of 4 μL/h for a 24-hour period, as well as the diffusion of a 150 μL GFP bolus with a concentration of 200 μg/mL over a 40-hour period, in a tissue-like phantom model made of gelatin. Further, the device was implanted into a living mouse for subcutaneous in vivo GFP recording as a proof of concept, and the fluorescence signal was successfully detected and recorded in the living animal.

MEMS-based piezoelectric ultrasonic energy harvesters (PUEH) have become one of the most promising options for replacing or transferring energy to batteries in medical implants, where device miniaturization and power optimization are needed. Among the most commonly used piezoelectric materials in PUEH, lead zirconate titanate (PZT) is widely acknowledged for its excellent piezoelectric properties, good stability, and low cost. However, the performance of PZT degrades when the processing temperature approaches and exceeds half of its Curie temperature Tc, limiting its application. Here, we demonstrate a highly miniaturized, low-temperature fabricated MEMS-based PUEH with an effective ultrasound harvesting area of 0.79 mm2 and an effective device volume of 0.35 mm3. The low-temperature adhesive epoxy bonding ensures the temperature throughout the entire fabrication process remains below 85°C, which preserves the properties of the integrated piezoelectric material to the greatest extent. This allows the use of bulk PZT-5H, a material that possesses superior piezoelectric properties, but has a relatively low Tc, to enhance device performance. Our device outputs a root-mean-square (RMS) voltage of 0.62 V and an RMS power of 0.19 mW on a 2 kΩ resistive load at an optimum operating frequency of 200 kHz, with a reception distance of 20 mm in water and input acoustic power intensity of 178 mW/cm2. The proposed design and fabrication technique enable our device to achieve the smallest effective size among the reported MEMS-based PUEH while still being capable of powering up numerous implantable medical devices and being compatible with various commercially available power management units. [2024-0081]