Intracellular delivery of therapeutic materials remains challenging, with conventional micropattern-assisted optoporation methods making it difficult to analyze the spatial effects of individual laser pulses. Here, we show that pigmented SU-8 microdisks enable precise analysis of distance-dependent shockwave effects on cell membrane permeabilization, achieving delivery yields up to 60% in optimized conditions. Using 20 μm and 50 μm microdisks irradiated by nanosecond laser pulses, we discovered that larger patterns generate more extensive shockwaves leading to increased cell damage over broader ranges, while smaller patterns maintain high delivery efficiency with minimal cellular disruption. Furthermore, cellular adhesion strength critically influences treatment outcomes: strongly adherent SAOS-2 cells showed remarkable resilience while weakly adherent HEK-293 cells experienced extensive damage at greater distances. Our results demonstrate how micropattern size and cell-specific properties determine the spatial extent and efficiency of shockwave-mediated delivery, providing a framework for optimizing intracellular delivery strategies while preserving cell viability.

Cancer early detection is one of the most challenging purposes of preventive medicine. Liquid biopsy represents a revolutionary approach, fostering access to early screening and increasing patients' compliance, two crucial issues in reaching the largest possible audience in prevention campaigns. To facilitate this approach, the deployment of innovative methods for easy manipulation of biological fluids and the availability of devices for the rapid and low-cost detection of biomarkers is essential. The aim of this study was the optimization of multifunctional Lab-On-Chips with the final aim of realizing a platform for oral carcinoma cells trapping from a complex biological fluid as saliva and for specific subcellular components like extracellular vesicles (EVs) from the neuroblastoma cell model. A set of different microfluidic building blocks was realized through poly-methyl methacrylate (PMMA) micromilling, microfabricated and functionalized to optimize surface chemistry for capturing tumor cells or EVs in multiple channels, assess working concentration for biological fluids and combine sample preparation with detection modules all in the same chip. After optimization, a proof-of-concept device was realized mimicking liquid biopsy analysis from saliva, a biological fluid readily available and with a high compliance from patients, useful for the early diagnosis of cancer.

Microneedles with porous internal structures can provide pathways for transdermal ionic current and drug delivery by penetrating the stratum corneum of the skin. However, conventional porous microneedle arrays are typically monolithic and rigid, limiting their flexibility and adaptability to curved skin surfaces. To address the issue, a method to directly integrate an array of porous microneedles to a flexible substrate is proposed, preserving their skin penetration capability while enhancing flexibility. The resulting array conforms to curved skin surfaces while effectively reducing transdermal ionic resistance. Numerical and analytical modeling demonstrates that the limited number of needles on a flexible array is sufficient to reduce transdermal resistance. Further, an enzymatic battery is combined to create a fully organic, porous microneedle-based bioelectric skin patch that can generate stable transdermal current suitable for stimulation and drug delivery applications.

Lateral flow immunoassays typically rely on optical tests conducted on paper strips. However, the 3D matrix of paper embedded with optical nanoparticles often limits detection sensitivity and the ability of detection instruments to capture signals. This study introduces a novel approach using a glass chip-based lateral flow immunoassay, with albumin as a typical biomarker for detection, enabling the presence of the signal on a flat surface. Compared with traditional paper-based immunoassay, glass-based lateral flow immunoassay has achieved a uniform distribution pattern for albumin detection, lowered the limit of detection from 100ng/mL to 1ng/mL, and reduced detection time through an improved liquid mobility system. The glass-based method also shortens the detection time by 28.5% to 147.8s compared to the traditional method. This research presents a new methodology for lateral flow immunoassays that can be applied to a wide range of biomarkers, with potential benefits for various medical and environmental applications.

Ventriculoperitoneal (VP) shunt obstruction, often caused by protein and fat accumulation at the ventricular catheter ports, impedes cerebrospinal fluid (CSF) outflow, increases intracranial pressure (ICP), and leads to hydrocephalus. Current treatments require invasive shunt removal, reimplantation, or retrograde flush cleansing. We present a next-generation VP shunt system that actively removes blockages via external actuation. Our system, called CLogging Elimination ActuatoR Silicone (CLEARS), integrates a soft, expandable silicone tube within the catheter lumen. This soft robotic insert, capable of 900% strain, can inflate to dislodge blockages and then deflate to restore flow. To test CLEARS, we developed an ex vivo model simulating CSF flow and obstruction using a rapidly acting clogging agent. ICP upstream of the catheter was monitored to evaluate performance. When obstructed with 3 g of the clogging agent, ICP rose to 30 cmH_2O. Upon CLEARS activation, the silicone insert expanded through catheter ports and successfully removed the clog, restoring baseline ICP (sim0 cmH_2O) within approximately 40 s. Without the system, obstruction persisted and pressure remained elevated. Visual documentation confirmed the mechanism of action. The CLEARS system offers a promising solution to VP shunt occlusion by enabling non-invasive mechanical declogging. Our model replicates shunt obstruction and CSF dynamics, providing a testbed for device evaluation. The expandable insert maintained catheter flow and reduced ICP to normal levels after obstruction, representing a potential shift in how hydrocephalus is treated.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10544-025-00769-8.

We report a centrifugal microfluidic device that automatically performs sample preparation under steady-state rotation for clinical applications using mass spectrometry. The autonomous microfluidic device was designed for the control of liquid operation on centrifugal hydrokinetics (CLOCK) paradigm. The reported device was highly stable, with less than 7% variation with respect to the time of each unit operation (sample extraction, mixing, and supernatant extraction) in the preparation process. An agitation mechanism with bubbling was used to mix the sample and organic solvent in this device. We confirmed that the device effectively removed the protein aggregates from the sample, and the performance was comparable to those of conventional manual sample preparation procedures that use high-speed centrifugation. In addition, probe electrospray ionization mass spectrometry (PESI-MS) was performed to compare the device-treated and manually treated samples. The obtained PESI-MS spectra were analyzed by partial least squares discriminant analysis, and the preparation capability of the device was found to be equivalent to that of the conventional method.

Non-coding RNA (ncRNA)-based therapeutics that induce RNA interference (RNAi), such as microRNAs (miRNAs), have drawn considerable attention as a novel class of targeted cancer therapeutics because of their capacity to specifically target oncogenes/protooncogenes that regulate key signaling pathways involved in carcinogenesis, tumor growth and progression, metastasis, cell survival, proliferation, angiogenesis, and drug resistance. However, clinical translation of miRNA-based therapeutics, in particular, has been challenging due to the ineffective delivery of ncRNA molecules into tumors and their uptake into cancer cells. Recently, superparamagnetic iron oxide-based nanoparticles (SPIONs) have emerged as highly effective and efficient for the delivery of therapeutic RNAs to malignant tissues, as well as theranostic (therapy and diagnostic) applications, due to their excellent biocompatibility, magnetic responsiveness, broad functional surface modification, safety, and biodistribution profiles. This review highlights recent advances in the use of SPIONs for the delivery of ncRNA-based therapeutics with an emphasis on their synthesis and coating strategies. Moreover, the advantages and current limitations of SPIONs and their future perspectives are discussed.

Direct 3D printing of active microfluidic elements on PCB substrates enables high-speed fabrication of stand-alone microdevices for a variety of health and energy applications. Microvalves are key components of microfluidic devices and liquid metal (LM) microvalves exhibit promising flow control in microsystems integrated with PCBs. In this paper, we demonstrate LM microvalves directly 3D printed on PCB using advanced digital light processing (DLP). Electrodes on PCB are coated by carbon ink to prevent alloying between gallium-based LM plug and copper electrodes. We used DLP 3D printers with in-house developed acrylic-based resins, Isobornyl Acrylate, and Diurethane Dimethacrylate (DUDMA) and functionalized PCB surface with acrylic-based resin for strong bonding. Valving seats are printed in a 3D caterpillar geometry with chamber diameter of 700 µm. We successfully printed channels and nozzles down to 90 µm. Aiming for microvalves for low-power applications, we applied square-wave voltage of 2 Vpp at a range of frequencies between 5 to 35 Hz. The results show precise control of the bistable valving mechanism based on electrochemical actuation of LMs.

Flow based deformation cytometry has shown potential for cell classification. We demonstrate the principle with an injection moulded microfluidic chip from which we capture videos of adult and fetal red blood cells, as they are being deformed in a microfluidic chip. Using a deep neural network - SlowFast - that takes the temporal behavior into account, we are able to discriminate between the cells with high accuracy. The accuracy was larger for adult blood cells than for fetal blood cells. However, no significant difference was observed between donors of the two types.

Surface acoustic waves in combination with microfluidics has become an attractive research field regarding its various medical and biological applications. It is sometimes preferred to solve just the fluid domain and apply some boundary conditions to represent other components rather than performing a coupled numerical solution. To account for the piezoelectric actuation, a conventional velocity distribution built by superposing the left-going and right-going surface waves is commonly used as the boundary condition, its correctness is assessed here by comparing it to a coupled solution. It was shown that the actual leaky surface acoustic wave in coupled solution has different wavelengths in its real and imaginary parts, sometimes gets out of being sinusoidal, and has a different form compared to the superposed formula. For the phase differences other than 0 and π between the left and right electrodes, the distance between the electrodes affects the streaming and acoustic fields in the microchannel thereby leading to deviations in particle traces. Furthermore, the ratio of the horizontal to vertical components of the surface wave was extracted from the coupled solutions and compared to its previously reported values. The sensitivity analysis showed that for small particles, this ratio does not affect the streaming pattern but changes its velocity magnitude causing a time lag. For larger particles, the ratio altered the movement direction. This study suggests not replacing the piezoelectric actuation with the boundary condition to avoid inaccuracy in resulting fields that are being used in calculations of particle tracing and acoustic radiation forces.