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Abstract Organoids are three-dimensional cell clusters derived from stem cells and closely resemble the physiological characteristics of human tissues. As the next-generation biological model, organoids provide new opportunities for drug discovery, disease modeling, and personalized medicine. To fully harness the potential of organoids, real-time monitoring of biological states and functional evaluation of organoids are crucial. This review highlights recent advances in real-time, in situ biosensing technologies, including microelectrode arrays for electrophysiological recordings, chemical sensors for biochemical detection, and strain sensors for monitoring mechanical properties. While the development of miniature sensors for non-invasive, long-term, and real-time monitoring of organoids is in the early stage, these sensors are an essential part of organoid technology which would provide new insights into human developmental biology, pathophysiology, and drug discovery. After reviewing the seminal works on the microfabricated sensors for organoids, we also provide an outlook of the field including a discussion on the remaining challenges and future directions with a focus on integration of multiple sensors to facilitate organoid research and applications.

Visualization of focused ultrasound in high spatial and temporal resolution is crucial for accurately and precisely targeting brain regions noninvasively. Magnetic resonance imaging (MRI) is the most widely used noninvasive tool for whole-brain imaging. However, focused ultrasound studies employing high-resolution (> 9.4 T) MRI in small animals are limited by the small size of the radiofrequency (RF) volume coil and the noise sensitivity of the image to external systems such as bulky ultrasound transducers. This technical note reports a miniaturized ultrasound transducer system packaged directly above a mouse brain for monitoring ultrasound-induced effects using high-resolution 9.4 T MRI. Our miniaturized system integrates MR-compatible materials with electromagnetic (EM) noise reduction techniques to demonstrate echo-planar imaging (EPI) signal changes in the mouse brain at various ultrasound acoustic intensities. The proposed ultrasound-MRI system will enable extensive research in the expanding field of ultrasound therapeutics.

Abstract Transcranial focused ultrasound stimulation (tFUS) is an effective noninvasive treatment modality for brain disorders with high clinical potential. However, the therapeutic effects of ultrasound neuromodulation are not widely explored due to limitations in preclinical systems. The current preclinical studies are head‐fixed, anesthesia‐dependent, and acute, limiting clinical translatability. Here, this work reports a general‐purpose ultrasound neuromodulation system for chronic, closed‐loop preclinical studies in freely behaving rodents. This work uses microelectromechanical systems (MEMS) technology to design and fabricate a small and lightweight transducer capable of artifact‐free stimulation and simultaneous neural recording. Using the general‐purpose system, it can be observed that state‐dependent ultrasound neuromodulation of the prefrontal cortex increases rapid eye movement (REM) sleep and protects spatial working memory to REM sleep deprivation. The system will allow explorative studies in brain disease therapeutics and neuromodulation using ultrasound stimulation for widespread clinical adoption.

Purpose: To report a case of corneal edema associated with Descemet membrane (DM) damage likely due to shockwave trauma from a bullet passing by the eye. Observations: A 27-year-old man presented to the emergency department with pain, redness, and severely decreased vision in the left eye immediately following a gun assault. Examination of the eye revealed a temporal conjunctival laceration, corneal edema, hyphema, and vitreous hemorrhage. Bullets were found in the patient's left chest and axilla, and a laceration was present on the bridge of his nose, but no foreign bodies were found in or around the eyes. The intraocular hemorrhage and corneal edema gradually resolved, and it became apparent that there were DM irregularities that possibly represented micro-ruptures. After 7 months, uncorrected visual acuity improved to 20/25, and the cornea was free of edema but had persistent small focal areas of DM thickening and scarring. Conclusions and Importance: This case illustrates that DM and possibly endothelial cell damage can occur due to shockwave injury from high-speed projectiles. In our case of presumed small central DM micro-ruptures, the corneal edema resolved, and the vision significantly improved with topical therapy and observation, suggesting an overall good prognosis from such injuries.

Microelectromechanical neural probes can cause tissue damage and often cannot record from distant brain areas. Here the authors combine electrical recording, optical stimulation and microfluidic drug delivery in one multi-shank probe with thinner shanks to reduce damage and a flexible design to target long-range neural circuits.

An acoustic matching layer is an essential component of an ultrasound transducer to achieve maximum ultrasound transmission efficiency. Here, we develop a flexible printed circuit board (FPCB) with a composite structure consisting of multiple polyimide and copper layers and demonstrate it as a novel acoustic matching layer. With a flexible substrate and robust ACF bonding, the FPCB not only serves as an acoustic matching layer between piezoelectric elements and the surrounding medium but also as a ground for the electrical connection between the transducer array elements and the folded substrate. A 1D linear ultrasound transducer array with the FPCB matching layer exhibits larger output pressure, wider -3dB bandwidth, and higher ultrasound beam intensity compared to that of an ultrasound transducer array with the alumina/epoxy matching layer, which is one of the most commonly applied composite matching layers. The enhanced transmission performance verifies that the proposed FPCB is an excellent matching layer for 1D linear ultrasound transducer arrays.

The development of portable volatile organic compound (VOC) sensors is essential for home healthcare and workplace safety because VOCs are environmental pollutants that may critically affect human health. Here, we report a compact and portable sensor platform based on a capacitive micromachined ultrasonic transducer (CMUT) array offering multiplex detection of various VOCs (toluene, acetone, ethanol, and methanol) using a single read-out system. Three CMUT resonant devices were functionalized with three different layers: (1) phenyl-selective peptide, (2) colloids of single-walled nanotubes and peptide, and (3) poly(styrene-co-allyl alcohol). As each device exhibited different sensitivities to the four VOCs, we performed principal component analysis to achieve selective detection of all four gases. For the simultaneous detection of VOCs using CMUT sensors, the changes in the resonant frequencies of three devices were monitored in real time, but using only a single oscillator through an electrically controlled relay to achieve compactness. In addition, by devising a wireless system, measurement results were transmitted to a smartphone to monitor the concentration of VOCs. We used multiple sensors to obtain a larger number of fingerprints for pattern recognition to enhance selectivity but interfaced these sensors with a single read-out circuit to minimize the footprint of the overall system. The compact CMUT-based sensor array based on a multiplex detection scheme is a promising sensor platform for portable VOC monitoring.

Chronic monitoring of bladder activity and urine volume is essential for patients suffering from urinary dysfunctions. However, due to the anatomy and dynamics of the bladder, chronic and precise monitoring of bladder activity remains a challenge. Here, we propose a new sensing mechanism that measures the bladder volume using a resistive ladder network with contact switches. Instead of measuring the impedance between the electrode continuously, the proposed sensor provides a digitized output (‘on’ or ‘off’) when the bladder volume reaches a certain threshold value. We present simple proof-of-concept sensors which compare the discrete-mode operation to the continuous-mode operation. In addition, by using multiple pairs of this contact-mode switch in a resistor ladder structure, we demonstrate monitoring of the bladder volume in four discrete steps using an idealized balloon and an ex vivo pig’s bladder. We implemented the resistive ladder network using a conductive polypyrrole/agarose hydrogel composite which exhibits a Young’s modulus comparable to that of the bladder wall. Compared to the continuous-mode operation, the proposed sensing mechanism is less susceptible to drift due to material degradation and environmental factors.

State-of-the-art 3-D medical ultrasound imaging requires transmitting and receiving ultrasound using a 2-D array of ultrasound transducers with hundreds or thousands of elements. A tight combination of the transducer array with integrated circuitry eliminates bulky cables connecting the elements of the transducer array to a separate system of electronics. Furthermore, preamplifiers located close to the array can lead to improved receive sensitivity. A combined IC and transducer array can lend to a portable, high-performance, and inexpensive 3-D ultrasound imaging system. This paper presents an IC flip-chip bonded to a 16 x 16-element capacitive micromachined ultrasonic transducer (CMUT) array for 3-D ultrasound imaging. The IC includes a transmit beamformer that generates 25-V unipolar pulses with programmable focusing delays to 224 of the 256 transducer elements. One-shot circuits allow adjustment of the pulse widths for different ultrasound transducer center frequencies. For receiving reflected ultrasound signals, the IC uses the 32-elements along the array diagonals. The IC provides each receiving element with a low-noise 25-MHz-bandwidth transimpedance amplifier. Using a field-programmable gate array (FPGA) clocked at 100 MHz to operate the IC, the IC generated properly timed transmit pulses with 5-as accuracy. With the IC flip-chip bonded to a CMUT array, we show that the IC can produce steered and focused ultrasound beams. We present 2-D and 3-D images of a wire phantom and 2-D orthogonal cross-sectional images (B-scans) of a latex heart phantom. [ABSTRACT FROM AUTHOR]