In situ self-referenced intracellular two-electrode system for enhanced accuracy in single-cell analysis.

Since the emergence of single-cell electroanalysis, the two-electrode system has become the predominant electrochemical system for real-time behavioral analysis of single-cell and multicellular populations. However, due to the transmembrane placement of the two electrodes, cellular activities can be interrupted by the transmembrane potentials, and the test results are susceptible to influences from factors such as intracellular solution, membrane, and bulk solution. These limitations impede the advancement of single-cell analysis. Here, we propose a highly miniaturized and integrated in situ self-referenced intracellular two-electrode system (IS-SRITES), wherein both the working and reference electrodes are positioned inside the cell. Additionally, we demonstrated the stability (0.28 mV/h) of the solid-contact in situ Ag/AgCl reference electrode and the ability of the system to conduct standard electrochemical testing in a wide pH range (pH 6.0-8.0). Cell experiments confirmed the non-destructive performance of the electrode system towards cells and its capacity for real-time monitoring of intra- and extracellular pH values. Moreover, through equivalent circuits, finite element simulations, and drug delivery experiments, we illustrated that the IS-SRITES can yield more accurate test results and exhibit enhanced resistance to interference from the extracellular environment. Our proposed system holds the potential to enable the precise detection of intracellular substances and optimize the existing model of the electrode system for intracellular signal detection, thereby spearheading advancements in single-cell analysis.

Multifunctional IrOx Neural Probe for In Situ Dynamic Brain Hypoxia Evaluation.

Perioperative cerebral hypoxia and neonatal hypoxia-ischemic encephalopathy are the main triggers that lead to temporary or permanent brain dysfunction. The pathogenesis is intimately correlated to neural activities and the pH of the microenvironment, which calls for a high demand for in situ multitype physiological signal acquisition in the brain. However, conventional pH sensing neural interfaces cannot obtain the characteristics of multimodes, multichannels, and high spatial resolution of physiological signals simultaneously. Here, we report a multifunctional implantable iridium oxide (IrOx) neural probe (MIIONP) combined with electrophysiology recording, in situ pH sensing, and neural stimulation for real-time dynamic brain hypoxia evaluation. The neural probe modified with IrOx films exhibits outstanding electrophysiology recording and neural stimulation performance and long-term stable high spatial pH sensing resolution of about 100 µm, and the cytotoxicity of IrOx microelectrodes was investigated as well. In addition, 4 weeks' tracking of the same neuron firing and instantaneous population spike captured during electrical stimulation was achieved by MIIONP. Finally, in a mouse brain hypoxia model, the MIIONP has demonstrated the capability of synchronous in situ recording of the pH and neural firing changes in the brain, which has a valuable application in dynamic brain disease evaluation through real-time acquisition of multiple physiological signals.

Wide Remote-Range and Accurate Wireless LC Temperature-Humidity Sensor Enabled by Efficient Mutual Interference Mitigation.

Inductor-capacitor wireless integrated sensors (LCWISs) featuring untethered and multitarget measurements are promising in health monitoring and human-machine interfaces. However, the lack of a profound understanding of the internal interference hinders the design of the LCWIS, which has a wide remote sensing range and high accuracy. Herein, a mutually exclusive effect of the mutual inductance interferences in LCWIS was revealed and quantified, enabling a design with a wide range of remote sensing (working distance comparable to the single-target device, working radius: 4 mm) and 16% reduced area. As a key to accurate multitarget measurement, a quantified target interference model based on interference decomposition was proposed to understand the target interferences, providing profound guidance for the design of ultra-accurate LCWIS. As a proof, we designed a cellulose-polyacrylate-cellulose LCWIS (CPC-LCWIS) with ultrahigh accuracies (∼1.2% RH and ∼0.18 °C) beyond commercial wired gauges. The CPC-LCWIS with full-coil sensing structures achieved exceptionally high sensitivities (0.36 MHz/°C and 0.25 MHz/% RH). The CPC-LCWIS was validated for health monitoring and human-machine interfaces. The concept studied in this work provides profound guidance for designing a high-performance flexible LCWIS for advanced wearable electronics.

A Piezoelectric MEMS Speaker with a Combined Function of a Silent Alarm.

To explore the versatility of speakers, a piezoelectric micro-electro-mechanical system (MEMS) speaker combining the function of a silent alarm is proposed, which mainly comprises a lead zirconate titanate (PZT) actuation layer and a rigid-flexible coupling supporting layer. Measurements performed on encapsulated prototypes mounted to an artificial ear simulator have revealed that, compared to a speaker with a rigid supporting layer, the sound pressure level (SPL) of the proposed piezoelectric MEMS speaker with a rigid-flexible coupling supporting layer is significantly higher and is especially higher by 4.1-20.1 dB in the frequency range from 20 Hz to 4.2 kHz, indicating that the rigid-flexible coupling supporting layer can improve the SPL significantly in low frequency. Moreover, the spectral distribution characteristic of its playback audio is similar to that of the commercial electromagnetic type. The device can also function as a silent alarm based on oral airflows in dangerous situations, as it performs well at recognizing words according to their unique voltage-signal characteristics, and can avoid the effects of external sound noise, body movement, long distance, and occlusion. This strategy provides inspiration for functional diversification of piezoelectric MEMS speakers.

A flexible neural implant with ultrathin substrate for low-invasive brain-computer interface applications.

Implantable brain-computer interface (BCI) devices are an effective tool to decipher fundamental brain mechanisms and treat neural diseases. However, traditional neural implants with rigid or bulky cross-sections cause trauma and decrease the quality of the neuronal signal. Here, we propose a MEMS-fabricated flexible interface device for BCI applications. The microdevice with a thin film substrate can be readily reduced to submicron scale for low-invasive implantation. An elaborate silicon shuttle with an improved structure is designed to reliably implant the flexible device into brain tissue. The flexible substrate is temporarily bonded to the silicon shuttle by polyethylene glycol. On the flexible substrate, eight electrodes with different diameters are distributed evenly for local field potential and neural spike recording, both of which are modified by Pt-black to enhance the charge storage capacity and reduce the impedance. The mechanical and electrochemical characteristics of this interface were investigated in vitro. In vivo, the small cross-section of the device promises reduced trauma, and the neuronal signals can still be recorded one month after implantation, demonstrating the promise of this kind of flexible BCI device as a low-invasive tool for brain-computer communication.

Fabrication and Characterization of Iridium Oxide pH Microelectrodes Based on Sputter Deposition Method.

pH value plays an important role in many fields such as chemistry and biology; therefore, rapid and accurate pH measurement is very important. Because of its advantages in preparation, wide test range, rapid response, and good biocompatibility, iridium oxide material has received more and more attention. In this paper, we present a method for preparing iridium oxide pH microelectrodes based on the sputter deposition method. The sputtering parameters of iridium oxide are also studied and optimized. Open-circuit potential tests show that microelectrodes exhibit near-Nernstian pH response with good linearity (about 60 mV/pH), fast response, high stability (a slight periodic fluctuation of potential change <2.5 mV in 24 h), and good reversibility in the pH range of 1.00-13.00.