Plant sap analysis typically relies on destructive sampling and immediate freezing, limiting field deployment and longitudinal studies. We introduce a minimally invasive microfluidic device that extracts sap from the stem of Solanum lycopersicum and dries it in situ, enabling storage analogous to dried blood spots in humans. Using both artificial phytohormone mixtures and tomato sap, we assessed the stability of dried samples stored at room temperature for up to seven days and observed no substantial degradation of key phytohormones. Device performance was further validated in a paired sampling experiment, showing strong agreement with a conventional stem severing method for tZR and ABA quantification. These findings demonstrate that dried sap sampling via a microfluidic device provides a practical, field ready alternative to destructive methods, supporting repeated sampling from the same plant and enabling longitudinal metabolic monitoring.

Continuous observation of molecular and cellular dynamics in vivo is critical for understanding disease progression and therapeutic response. Conventional approaches, such as imaging or endpoint assays, are limited by their discontinuous nature and the physiological stress they impose on animal models. Here, we present a minimally invasive millimetric implantable device (5 × 5 × 5 mm³) designed for fully autonomous, continuous in vivo fluorescence tracking. The device integrates a miniaturized optical system with low-power on-board electronics, enabling uninterrupted fluorescence recording in close proximity to the biological source. We validated the device by tracking sustained release and systemic clearance of fluorescein isothiocyanate in vivo over 30 h. We further demonstrated long-term utility by continuously tracking tumor-associated fluorescence in a subcutaneous glioma model for 2 weeks. These results present a compact, self-contained device enabling continuous longitudinal fluorescence sensing in animal models, providing a platform for investigating drug delivery, tumor development, and immunological processes in their native microenvironments.

Integrated optical microsystems are key to next-generation communication, sensing, and quantum technologies, with the potential to exceed the capabilities of conventional microelectronics. Such systems rely on precise control of light, but creating optimal 3D micro-optics is challenging for conventional microfabrication technologies. Multiphoton lithography (MPL) offers nanoscale 3D printing capabilities, while efforts to extend MPL to high-performance glasses typically involve harsh high-temperature or chemical postprocessing that is incompatible with integrated optical microsystems. To address this, we explore the use of hydrogen silsesquioxane (HSQ), an inorganic precursor, for MPL. We demonstrate postprocessing-free 3D printing of solid silica glass and self-forming glass nanogratings with nanoscale resolution. These advances enable the direct integration of glass micro-optics on photonic chips and optical fibers. We present functional 3D-printed glass optical devices, including on-chip ring resonators and photoluminescent sources, and fiber-tip refractive index sensors and polarization beam splitters, opening new avenues for high-performance optical microsystem integration.

3D printing at the macroscale has evolved from making plastic prototypes to the production of high-performance functional metal parts for industries such as medical and aerospace. By contrast, MEMS devices today are produced in large quantities using semiconductor manufacturing processes. However, the semiconductor manufacturing paradigm is not cost-effective for producing customized MEMS devices in small to medium volumes (tens to thousands of units per year), and related applications are difficult to address efficiently. 3D printing of functional MEMS devices could play an important role in filling this gap. Here, we discuss recent advances in 3D- printed functional MEMS, addressing the challenges of economical customization at smaller production volumes.

We present a fabrication process for 3D printing of glass sensors directly onto the end of optical fiber tips. Compared to conventional polymeric 3D-printed fiber-tip sensors, our method provides far superior chemical resistance and mechanical durability. We demonstrate the utility of our sensors by reliably measuring the refractive index of aggressive organic solvents - environments where polymer-based sensors are prone to swelling and deformation. This breakthrough opens new avenues for deploying robust glass sensors in demanding industrial settings, such as chemical processing plants and oil refineries, where precise and durable refractive index measurements are essential.

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.

Single-molecule trapping and analysis are critical in understanding biomolecular processes at an unprecedented resolution. Traditional nanopore systems often face limitations in scalability and integration with electronic components, which complicates their use in compact, high-density applications. Addressing these challenges, we introduce a novel on-chip nanopore array system integrated with a silver (Ag) electrode and self-aligned femtolitersized cavities, representing an innovative approach for electronic single-molecule trapping. Our design utilizes a wafer-scale fabrication process with a buried electrode architecture, enabling the scalable production of high-density nanopore arrays without the need for through-wafer etching. Successful DNA translocation measurements demonstrate the system's potential as a versatile platform for single-molecule trapping and reaction studies.

Controlled breakdown has emerged as an effective method for fabricating solid-state nanopores in thin suspended dielectric membranes for various biomolecular sensing applications. On an unpatterned membrane, the site of nanopore formation by controlled breakdown is random. Nanopore formation on a specific site on the membrane has previously been realized using local thinning of the membrane by lithographic processes or laser-assisted photothermal etching under immersion in an aqueous salt solution. However, these approaches require elaborate and expensive cleanroom-based lithography processes or involve intricate procedures using custom-made equipment. Here, we present a rapid cleanroom-free approach using single pulse femtosecond laser exposures of 50 nm thick silicon nitride membranes in air to localize the site of nanopore formation by subsequent controlled breakdown to an area less than 500 nm in diameter on the membrane. The precise positioning of the nanopores on the membrane could be produced both using laser exposure powers which caused significant thinning of the silicon nitride membrane (up to 60% of the original thickness locally), as well as at laser powers which caused no visible modification of the membrane at all. We show that nanopores made using our approach can work as single-molecule sensors by performing dsDNA translocation experiments. Due to the applicability of femtosecond laser processing to a wide range of membrane materials, we expect our approach to simplify the fabrication of localized nanopores by controlled breakdown in a variety of thin film material stacks, thereby enabling more sophisticated nanopore sensors.

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.

Topical drug delivery offers a localized and patient-friendly method for treating skin diseases and subcutaneous lesions. However, the outermost skin barrier - the stratum corneum (SC) - hinders the delivery of large molecules such as biopharmaceuticals. This study introduces rolling ultraminiaturized microneedle spheres (RUMS) as a novel solution that enables topical delivery of messenger RNA (mRNA) without the need for chemical enhancers or techniques like electroporation, iontophoresis, or microneedle patches. RUMS are engineered spherical microparticles that gently roll over the skin, creating numerous micropores while minimizing tissue damage. In ex vivo porcine skin experiments, 25 RUMS generated approximately 4,500 pores within 10 seconds, achieving penetration depths of around 20 micrometers and increasing skin permeability by up to 100-fold. In vivo studies in mice showed that combining RUMS with topical doxycycline led to a ~50% tumor size reduction within two weeks and full recovery by four weeks. In contrast, doxycycline or RUMS alone offered limited therapeutic benefit. Rapid skin healing was observed due to the small pore size. Additionally, topical delivery of lipid nanoparticle-encapsulated luciferase (luc)-encoding mRNA was successfully demonstrated in mice. Overall, use of RUMS presents a simple, painless, and potentially well-tolerated technique for enabling transdermal topical delivery of biologics.