Targeted stem cell delivery utilizing a magnetic actuation system is an emerging technology in stem cell engineering that efficiently targets stem cells in specific areas in vitro. However, integrating precise magnetic control systems with selective neural differentiation has not yet been widely considered for building successful neural networks. Challenges arise in creating targeted functional neuronal networks, largely due to difficulties in simultaneously controlling the positions of stem cells and selectively stimulating their differentiation. These challenges often result in suboptimal differentiation rates and abnormalities in transplanted neural stem cells. In contrast, ultrasound stimulation has superior tissue penetration and focusing capability, and represents a promising noninvasive neural stimulation technique capable of modulating neural activity and promoting selective differentiation into neuronal stem cells. In this study, we introduce a method for targeted neural differentiation using localized ultrasonic stimulation with a piezoelectric micromachined ultrasound transducer (pMUT) array. Differentiation was assessed quantitatively by monitoring neurite outgrowth as the ultrasound intensity was increased. The neurite length of cells ultrasonically stimulated for 40 min was found to have increased, compared to the non-stimulated group (119.9 ± 34.3 μm vs. 63.2 ± 17.3 μm, respectively). Targeted differentiation was confirmed by measuring neurite lengths, where selective ultrasound stimulation induced differentiation in cells that were precisely delivered via an electromagnetic system. Magnetic cell-based robots reaching the area of localized ultrasound stimulation were confirmed to have enhanced differentiation. This research demonstrated the potential of the combination of precise stem cell delivery with selective neural differentiation to establish functional neural networks.

A tip-tilt-piston 3 × 3 electrothermal micromirror array (MMA) integrated with temperature field-based position sensors is designed and fabricated in this work. The size of the individual octagonal mirror plates is as large as 1.6 mm × 1.6 mm. Thermal isolation structures are embedded to reduce the thermal coupling among the micromirror units. Results show that each micromirror unit has a piston scan range of 218 μm and a tip-tilt optical scan angle of 21° at only 5 Vdc. The micromirrors also exhibit good dynamic performance with a rise time of 51.2 ms and a fall time of 53.6 ms. Moreover, the on-chip position sensors are proven to be capable for covering the full-range movement of the mirror plate, with the measured sensitivities of 1.5 mV/μm and 8.8 mV/° in piston sensing and tip-tilt sensing, respectively. Furthermore, the thermal crosstalk in an operating MMA has been experimentally studied. The measured results are promising thanks to the embedded thermal isolation structures.

In recent years, microfluidic systems have evolved to incorporate increasingly complex multi-layer and multi-material structures. While conventional 2-dimensional microfluidic systems are typically fabricated with lithographic techniques, the increase in system complexity necessitates a more versatile set of fabrication techniques. Similarly, although 3D printing can easily produce intricate microfluidic geometries, integrating multiple membranes and electrode components remains challenging. This study proposes a toolkit for fabricating free-standing 3-dimensional microfluidic systems for biomedical devices, incorporating flow channels, electrodes, and membranes. The fabrication techniques include molding separation using 3D printed molds, laser-based processing, and component assembly, each achieving micron resolution. Here, we introduce a novel approach to integrate membranes into microfluidics by directly curing elastomer-based microfluidics with the membrane through replica molding, while preserving membrane functionality by effectively removing elastomer residues through reactive ion etching. The resulting membrane-elastomer microfluidic component significantly simplifies the assembly of intricate microfluidic systems, reducing the device size to millimeter dimensions, suitable for implantable applications. The toolkit’s versatility is demonstrated by a redox flow iontophoretic drug delivery prototype at the millimeter scale, featuring two electrodes, four membranes, and four microfluidic channels.

Microelectronic magnetic sensors are essential in diverse applications, including automotive, industrial, and consumer electronics. Hall-effect devices hold the largest share of the magnetic sensor market, and they are particularly valued for their reliability, low cost and CMOS compatibility. This paper introduces a novel 3-axis Hall-effect sensor element based on an inverted pyramid structure, realized by leveraging MEMS micromachining and CMOS processing. The devices are manufactured by etching the pyramid openings with TMAH and implanting the sloped walls with n-dopants to define the active area. Through the use of various bias-sense detection modes, the device is able to detect both in-plane and out-of-plane magnetic fields within a single compact structure. In addition, the offset can be significantly reduced by one to three orders of magnitude by employing the current-spinning method. The device presented in this work demonstrated high in-plane and out-of-plane current- and voltage-related sensitivities ranging between 64.1 to 198 V A−1 T−1 and 14.8 to 21.4 mV V−1 T−1, with crosstalk below 4.7%. The sensor exhibits a thermal noise floor which corresponds to approximately 0.5μT/Hz at 1.31 V supply. This novel Hall-effect sensor represents a promising and simpler alternative to existing state-of-the-art 3-axis magnetic sensors, offering a viable solution for precise and reliable magnetic field sensing in various applications such as position feedback and power monitoring.

The use of bulk piezoelectric transducer arrays in medical imaging is a well-established technology that operates based on thickness mode piezoelectric vibration. Meanwhile, advancements in fabrication techniques have led to the emergence of micromachined alternatives, namely, piezoelectric micromachined ultrasound transducer (PMUT) and capacitive micromachined ultrasound transducer (CMUT). These devices operate in flexural mode using piezoelectric thin films and electrostatic forces, respectively. In addition, the development of flexible ultrasound transducers based on these principles has opened up new possibilities for biomedical applications, including biomedical imaging, sensing, and stimulation. This review provides a detailed discussion of the need for flexible micromachined ultrasound transducers (MUTs) and potential applications, their specifications, materials, fabrication, and electronics integration. Specifically, the review covers fabrication approaches and compares the performance specifications of flexible PMUTs and CMUTs, including resonance frequency, sensitivity, flexibility, and other relevant factors. Finally, the review concludes with an outlook on the challenges and opportunities associated with the realization of efficient MUTs with high performance and flexibility.

Droplet microfluidics enable high-throughput screening, sequencing, and formulation of biological and chemical systems at the microscale. Such devices are generally fabricated in a soft polymer such as polydimethylsiloxane (PDMS). However, developing design masks for PDMS devices can be a slow and expensive process, requiring an internal cleanroom facility or using an external vendor. Here, we present the first complete droplet-based component library using low-cost rapid prototyping and electrode integration. This fabrication method for droplet microfluidic devices costs less than $12 per device and a full design-build-test cycle can be completed within a day. Discrete microfluidic components for droplet generation, re-injection, picoinjection, anchoring, fluorescence sensing, and sorting were built and characterized. These devices are biocompatible, low-cost, and high-throughput. To show its ability to perform multistep workflows, these components were used to assemble droplet “pixel" arrays, where droplets were generated, sensed, sorted, and anchored onto a grid to produce images.

Cardiovascular diseases account for ~40% of global deaths annually. This situation has revealed the urgent need for the investigation and development of corresponding drugs for pathogenesis due to the complexity of research methods and detection techniques. An in vitro cardiomyocyte model is commonly used for cardiac drug screening and disease modeling since it can respond to microphysiological environmental variations through mechanoelectric feedback. Microfluidic platforms are capable of accurate fluid control and integration with analysis and detection techniques. Therefore, various microfluidic platforms (i.e., heart-on-a-chip) have been applied for the reconstruction of the physiological environment and detection of signals from cardiomyocytes. They have demonstrated advantages in mimicking the cardiovascular structure and function in vitro and in monitoring electromechanical signals. This review presents a summary of the methods and technologies used to monitor the contractility and electrophysiological signals of cardiomyocytes within microfluidic platforms. Then, applications in common cardiac drug screening and cardiovascular disease modeling are presented, followed by design strategies for enhancing physiology studies. Finally, we discuss prospects in the tissue engineering and sensing techniques of microfluidic platforms.

Optomechanical sensors provide a platform for probing acoustic/vibrational properties at the micro-scale. Here, we used cavity optomechanical sensors to interrogate the acoustic environment of adjacent air bubbles in water. We report experimental observations of the volume acoustic modes of these bubbles, including both the fundamental Minnaert breathing mode and a family of higher-order modes extending into the megahertz frequency range. Bubbles were placed on or near optomechanical sensors having a noise floor substantially determined by ambient medium fluctuations, and which are thus able to detect thermal motions of proximate objects. Bubble motions could be coupled to the sensor through both air (i.e., with the sensor inside the bubble) and water, verifying that sound is radiated by the high-order modes. We also present evidence for elastic-Purcell-effect modifications of the sensor’s vibrational spectrum when encapsulated by a bubble, in the form of cavity-modified linewidths and line shifts. Our results could increase the understanding of bubble acoustics relevant to a variety of fields such as lab-on-a-chip microfluidics and biosensing, and could also inform future efforts to optimize the properties of micro-mechanical oscillators.

Living cells can rapidly adjust their metabolic activities in response to external stimuli, leading to fluctuations in intracellular temperature and reactive oxygen species (ROS) levels. Monitoring these parameters is essential for understanding cellular metabolism, particularly during dynamic biological processes. In this study, we present a bifunctional nanoprobe capable of simultaneous measurement of ROS levels and temperature within single cells. The nanoprobe features two individually addressable nanoelectrodes, with platinum (Pt) and nickel (Ni) coatings on both sides. At the tip, these two metal layers form a nano-thermocouple, enabling precise intracellular temperature measurements, while the Pt layer facilitates selective ROS detection. This dual functionality allows for real-time monitoring of cellular responses during synergistic chemo-photothermal therapy of cancer cells and zebrafish embryos subjected to mitochondrial toxic stress. Our results demonstrate that the nanoprobe effectively measures increases in temperature and ROS levels in HeLa cells undergoing chemo-photothermal therapy, as well as in chemically stimulated zebrafish embryos. By providing detailed analysis of submicrometer-scale temperature and ROS variations within living cells, this nanoprobe offers valuable insights into cellular processes and holds promise for early disease detection and drug development.

MEMS gyroscopes are well known for their outstanding advantages in Cost Size Weight and Power (CSWaP), which have inspired great research attention in recent years. A higher signal-to-noise ratio (SNR) for MEMS gyroscopes operating at larger vibrating amplitudes provides improved measuring resolution and ARW performance. However, the increment of amplitude causes strong nonlinear effects of MEMS gyroscopes due to their micron size, which has negative influences on the performance. This paper carries out detailed research on a general nonlinear mechanism on the sensors using parallel-plate capacitive transducers, which is called the gain nonlinearity in electrostatic actuation. The theoretical model established in this paper demonstrates the actuation gain nonlinearity causes the control-force coupling and brings extra angle-dependent bias with the 4th component for the whole-angle gyroscopes, which are verified by the experiments carried out on a micro-shell resonator gyroscope (MSRG). Furthermore, a real-time correction method is proposed to restore a linear response of the electrostatic actuation, which is realized by the gain modification with an online parameter estimation based on the harmonic-component relationship of capacitive detection. This real-time correction method could reduce the 4th component of the angle-dependent bias by over 95% from 0.003°/s to less than 0.0001°/s even under different temperatures. After the correction of actuation gain nonlinearity, the bias instability (BI) of whole-angle MSRG is improved by about 3.5 times from 0.101°/h to 0.029°/h and the scale factor nonlinearity (SFN) is reduced by almost one order of magnitude from 2.02 ppm to 0.21 ppm.