Proinflammatory polarization of engineered heat-inducible macrophages reprogram the tumor immune microenvironment during cancer immunotherapy.

The success of macrophage-based adoptive cell therapy is largely constrained by poor polarization from alternatively activated (M2-like) to classically activated (M1-like) phenotype in the immunosuppressive tumor microenvironment (TME). Here, we show that the engineered macrophage (eMac) with a heat-inducible genetic switch can induce both self-polarization of adoptively transferred eMac and re-polarization of tumour-associated macrophages in response to mild temperature elevation in a mouse model. The locoregional production of proinflammatory cytokines by eMac in the TME dose not only induces the strong polarization of macrophages into a classically activated phenotype, but also ensures that the side effects typical for systemically administrate proinflammatory cytokines are avoided. We also present a wearable warming device which is adaptable for human patients and can be remotely controlled by a smartphone. In summary, our work represents a safe and efficient adoptive transfer immunotherapy method with potential for human translation.

Magnetically Compatible Brain Electrode Arrays Based on Single-Walled Carbon Nanotubes for Long-Term Implantation.

Advancements in brain-machine interfaces and neurological treatments urgently require the development of improved brain electrodes applied for long-term implantation, where traditional and polymer options face challenges like size, tissue damage, and signal quality. Carbon nanotubes are emerging as a promising alternative, combining excellent electronic properties and biocompatibility, which ensure better neuron coupling and stable signal acquisition. In this study, a new flexible brain electrode array based on 99.99% purity of single-walled carbon nanotubes (SWCNTs) was developed, which has 30 um × 40 um size, about 5.1 kΩ impedance, and 14.01 dB signal-to-noise ratio (SNR). The long-term implantation experiment in vivo in mice shows the proposed brain electrode can maintain stable LFP signal acquisition over 12 weeks while still achieving an SNR of 3.52 dB. The histological analysis results show that SWCNT-based brain electrodes induced minimal tissue damage and showed significantly reduced glial cell responses compared to platinum wire electrodes. Long-term stability comes from SWCNT's biocompatibility and chemical inertness, the electrode's flexible and fine structure. Furthermore, the new brain electrode array can function effectively during 7-Tesla magnetic resonance imaging, enabling the collection of local field potential and even epileptic discharges during the magnetic scan. This study provides a comprehensive study of carbon nanotubes as invasive brain electrodes, providing a new path to address the challenge of long-term brain electrode implantation.

Microfluidic devices integrated with plasmonic nanostructures for sensitive fluorescent immunoassays.

The robust identification and quantification of various biomarkers is of utmost significance in clinical diagnostics and precision medicine. Fluorescent immunoassays are widely used and considered as a gold standard for biomarker detection due to their high specificity and accuracy. However, current commercial immunoassay tests suffer from limited detection sensitivity and complicated, labor-intensive operation procedures, making them impractical for point-of-care diagnosis, particularly in resource-limited regions. Recently, microfluidic immunoassay devices integrated with plasmonic nanostructures have emerged as a powerful tool for sensitive detection of biomarkers, addressing specific issues, such as integration schemes, easy operation, multiplexed detection, and sensitivity enhancement. In this paper, we provide a discussion on the recent advances in the plasmonic nanostructures integrated with microfluidic devices for fluorescent immunoassays. We shed light on the nanofabrication strategies and various fluidic designs for rapid, sensitive, and highly efficient sensing of antigens. Finally, we share our perspectives on the potential directions of these integrated devices for practical applications.

Flexible Film Bulk Acoustic Wave Filter Based on Poly(vinylidene fluoride-trifluorethylene).

Poly(vinylidene fluoride-trifluorethylene) (P(VDF-TrFE)) has promising potential applications in radio-frequency filters due to their excellent piezoelectric properties, flexibility, and stability. In this paper, a flexible film bulk acoustic wave filter is investigated based on P(VDF-TrFE) as piezoelectric film. A new method based on three-step annealing is developed to efficiently remove the porosity inside the P(VDF-TrFE) films so as to improve its properties. The obtained film achieved high ß-phase content beyond 80% and a high piezoelectric coefficient of 27.75 pm/V. Based on the low porosity ß-phase films, a flexible wide-band RF filter is designed, which consists of a bulk acoustic wave resonator and lumped inductor-capacitor elements as a hybrid configuration. The resonator sets the filter's center frequency, while the lumped LC-based matching network extends the bandwidth and enhances out-of-band rejection. The testing results of the proposed wide-band filter show its good performance, with 12.5% fractional bandwidth and an insertion loss of 3.1 dB. To verify the possibility of folding and stacking the flexible bulk acoustic wave devices for high-density multi-filter integration in MIMO communication, bending tests of the filter are also conducted with the bending strain range up to 5500 µÎµ. The testing results show no noticeable performance degradation after four bending cycles. This work demonstrates the potential of ß-phase P(VDF-TrFE) bulk acoustic wave filters to expand the scope of future flexible radio-frequency filter applications.

Novel Sandwich-Structured Flexible Composite Films with Enhanced Piezoelectric Performance.

Piezoelectric poly(vinylidene fluoride) (PVDF) and its copolymers have been widely investigated for applications in wearable electric devices and sensing systems, owing to their intrinsic piezoelectricity and superior flexibility. However, their weak piezoelectricity poses major challenges for practical applications. To overcome these challenges, we propose a two-step synthesis approach to fabricate sandwich-structured piezoelectric films (BaTiO3@PDA/PVDF/BaTiO3@PDA) with significantly enhanced ferroelectric and piezoelectric properties. As compared to pristine PVDF films or conventional 0-3 composite films, a maximum polarization (Pmax) of 11.24 µC/cm2, a remanent polarization (Pr) of 5.83 µC/cm2, and an enhanced piezoelectric coefficient (d33 ∼ 14.6 pC/N) were achieved. Simulation and experimental results have demonstrated that the sandwich structure enhances the ability of composite films to withstand higher poling electric fields in comparison with 0-3 composites. The sandwich-structured piezoelectric films are further integrated into a wireless sensor system with a high force sensitivity of 288 mV/N, demonstrating great potential for movement monitoring applications. This facile approach shows great promise for the large-scale production of composite films with remarkable flexibility, ferroelectricity, and piezoelectricity for wearable sensing devices.

High Electromechanical Coupling Coefficient of Longitudinally Excited Shear Wave Resonator Based on Optimized Bragg Structure.

In this work, a longitudinally excited shear-wave resonator (YBAR) based on single-crystalline lithium tantalate (LiTaO3, LT) thin film is proposed. The YBAR has a 200 nm X-cut thin film and molybdenum electrode. A high effective electromechanical coupling coefficient (k2eff) of up to 19% for the suspension-type structure was obtained. Furthermore, a Bragg reflector (SiO2/Pt) with optimized layer thickness ratio was employed to improve the performance of the YBAR. Compared to the acoustic wave resonators with the conventional quarter-wave (λ/4) Bragg reflector, the proposed YBAR with an optimized Bragg reflector can reflect both the longitudinal and shear waves efficiently, and resonators with spurious-free response and high quality (Q) value were achieved. This work provides a potential solution to enabling high coupling micro-acoustic resonators with high Q factor in the 5G/6G communication system.

High-Throughput Microfluidic Production of Droplets and Hydrogel Microspheres through Monolithically Integrated Microchannel Plates.

In this paper, we present a highly effective microfluidic emulsion system using an integrated microchannel plate (MCP), a porous glass membrane that is readily available and densely packs millions of through-microchannels, for high-throughput production of monodisperse droplets. The physical controls of droplet formation, including viscosity, flow rate, and pore size, have been extensively explored for optimum emulsification conditions. The performance of the device has been validated where monodisperse droplets with a narrow coefficient of variance (<5%) can be achieved at a dispersed phase flux of 3 mL h-1 from a piece of 4 × 4 mm2 MCP. The average droplet size is two times the nominal membrane pore diameter and thus can be easily controlled by choosing the appropriate membrane type. The preparation of hydrogel microspheres has also been demonstrated with a high throughput of 1.5 × 106 particles min-1. These microspheres with a uniform size range and rough surface morphology provide suitable bioenvironments and serve as ideal carriers for cell culture. Mouse fibroblasts are shown to be cultured on these 3D scaffolds with an average cell viability of over 96%. The cell attachment rate can reach up to 112 ± 7% in 24 h and the proliferation ability increases with the number of culture days. Furthermore, the device has been applied in the droplet digital polymerase chain reaction for absolute quantification of lung cancer-related PLAU genes. The detection limit achieved was noted to be 0.5 copies/µL with a dynamic range of 105 ranging from 1 × 102 to 1 × 106 copies/µL. Given the easy fabrication, robust performance, and simple operation, the emulsion system sets the stage for the laboratory's droplet-based assays and applications in tissue engineering.

Analytical and experimental study of a valveless piezoelectric micropump with high flowrate and pressure load.

Miniaturized gas pumps based on electromagnetic effect have been intensively studied and widely applied in industries. However, the electromagnetic effect-based gas pumps normally have large sizes, high levels of noises and high power consumption, thus they are not suitable for wearable/portable applications. Herein, we propose a high-flowrate and high-pressure load valveless piezoelectric micropump with dimensions of 16 mm*16 mm*5 mm. The working frequency, vibration mode and displacement of the piezoelectric actuator, the velocity of gas flow, and the volume flowrate of the micropump are analyzed using the finite element analysis method. The maximum vibration amplitude of the piezoelectric actuator reaches ~29.4 µm. The output gas flowrate of the pump is approximately 135 mL/min, and the maximum output pressure exceeds 40 kPa. Then, a prototype of the piezoelectric micropump is fabricated. Results show that performance of the micropump is highly consistent with the numerical analysis with a high flowrate and pressure load, demonstrated its great potential for wearable/portable applications, especially for blood pressure monitoring.

Machine Learning Assisted Wearable Wireless Device for Sleep Apnea Syndrome Diagnosis.

Sleep apnea syndrome (SAS) is a common but underdiagnosed health problem related to impaired quality of life and increased cardiovascular risk. In order to solve the problem of complicated and expensive operation procedures for clinical diagnosis of sleep apnea, here we propose a small and low-cost wearable apnea diagnostic system. The system uses a photoplethysmography (PPG) optical sensor to collect human pulse wave signals and blood oxygen saturation synchronously. Then multiscale entropy and random forest algorithms are used to process the PPG signal for analysis and diagnosis of sleep apnea. The SAS determination is based on the comprehensive diagnosis of the PPG signal and blood oxygen saturation signal, and the blood oxygen is used to exclude the error induced by non-pathological factors. The performance of the system is compared with the Compumedics Grael PSG (Polysomnography) sleep monitoring system. This simple diagnostic system provides a feasible technical solution for portable and low-cost screening and diagnosis of SAS patients with a high accuracy of over 85%.

Current crowding in graphene-silicon schottky diodes.

The performance of the Graphene/Si (Gr/Si) Schottky interface and its potential in future electronics strongly rely on the quality of interconnecting contacts with external circuitry. In this work, we investigate the dominating and limiting factors of Gr/Si interfaces designed for high light absorption, paying particular attention to the nature of the contact failure under high electrostatic discharge (ESD) conditions. Our findings indicate that severe current crowding at contact edges of the graphene is the dominating factor for the device breakdown. Material degradation and electrical breakdown are systematically analyzed by atomic force, Raman, scanning electron, and energy-dispersive x-ray spectroscopies. This work enlists the robustness and limitations of Gr/Si junction in photodiode architecture under high ESD conditions that can be used as general guidelines for 2D-3D electronic and optoelectronic devices.

Numerical Study of Particle Separation through Integrated Multi-Stage Surface Acoustic Waves and Modulated Driving Signals.

The manipulation of biomedical particles, such as separating circulating tumor cells from blood, based on standing surface acoustic wave (SSAW) has been widely used due to its advantages of label-free approaches and good biocompatibility. However, most of the existing SSAW-based separation technologies are dedicated to isolate bioparticles in only two different sizes. It is still challenging to fractionate various particles in more than two different sizes with high efficiency and accuracy. In this work, to tackle the problems of low efficiency for multiple cell particle separation, integrated multi-stage SSAW devices with different wavelengths driven by modulated signals were designed and studied. A three-dimensional microfluidic device model was proposed and analyzed using the finite element method (FEM). In addition, the effect of the slanted angle, acoustic pressure, and the resonant frequency of the SAW device on the particle separation were systemically studied. From the theoretical results, the separation efficiency of three different size particles based on the multi-stage SSAW devices reached 99%, which was significantly improved compared with conventional single-stage SSAW devices.

Multifunctional Evaluation Technology for Diagnosing Malfunctions of Regional Pelvic Floor Muscles Based on Stretchable Electrode Array Probe.

The pelvic floor dysfunction (PFD) has become a serious public health problem. Accurate diagnosis of regional pelvic floor muscle (PFM) malfunctions is vitally important for the prevention and treatment of PFD. However, there is a lack of reliable diagnostic devices to evaluate and diagnose regional PFM abnormality. In this work, we developed a multifunctional evaluation technology (MET) based on a novel airbag-type stretchable electrode array probe (ASEA) for the diagnosis of malfunctions of regional PFM. The inflatable ASEA has specifically distributed 32 electrodes along the muscles, and is able to adapt to different human bodies for tight contact with the muscles. These allow synchronous collection of high-quality multi-channel surface electromyography (MC-sEMG) signals, and then are used to diagnose regional PFM malfunctions and evaluate inter-regional correlation. Clinical trial was conducted on 15 postpartum stress urinary incontinence (PSUI) patients and 15 matched asymptomatic women. Results showed that SUI patients responded slowly to the command and have symptoms of muscle strength degeneration. The results were consistent with the relevant clinical manifestations, and proved the reliability of MET for multifunctional PFM evaluation. Furthermore, the MET can diagnose malfunctions of regional PFM, which is inaccessible with existing technology. The results also showed that the dysfunction of PSUI patients is mainly located in iliococcygeus, pubococcygeus, and urethral sphincter regions, and there is a weak correlation between these specific regions and nearby regions. In conclusion, MET provides a point-of-care diagnostic method for abnormal function of regional PFM, which has a potential for the targeted point-to-point electrical stimulation treatment and PFD pathology research.

The emerging landscape of microfluidic applications in DNA data storage.

DNA has been considered a promising alternative to the current solid-state devices for digital information storage. The past decade has witnessed tremendous progress in the field of DNA data storage contributed by researchers from various disciplines. However, the current development status of DNA storage is still far from practical use, mainly due to its high material cost and time consumption for data reading/writing, as well as the lack of a comprehensive, automated, and integrated system. Microfluidics, being capable of handling and processing micro-scale fluid samples in a massively paralleled and highly integrated manner, has gradually been recognized as a promising candidate for addressing the aforementioned issues. In this review, we provide a discussion on recent efforts of applying microfluidics to advance the development of DNA data storage. Moreover, to showcase the tremendous potential that microfluidics can contribute to this field, we will further highlight the recent advancements of applying microfluidics to the key functional modules within the DNA data storage workflow. Finally, we share our perspectives on future directions for how to continue the infusion of microfluidics with DNA data storage and how to advance toward a truly integrated system and reach real-life applications.

Flexible Film Bulk Acoustic Resonator Based on Low-Porosity ß-Phase P(VDF-TrFE) Film for Human Vital Signs Monitoring.

P(VDF-TrFE) is a promising material for flexible acoustic devices owing to its good piezoelectric performance and excellent stretchability. However, the high density of internal pores and large surface roughness of the conventional P(VDF-TrFE) results in a high propagation attenuation for acoustic waves, which limits its use in flexible acoustic devices. In this paper, a novel method based on two-step annealing is proposed to effectively remove the pores inside the P(VDF-TrFE) film and reduce its surface roughness. The obtained P(VDF-TrFE) film possesses excellent characteristics, including a high breakdown strength of >300 kV/mm, a high-purity ß-phase content of more than 80%, and high piezoelectric coefficients (d33) of 42 pm/V. Based on the low-porosity ß-phase P(VDF-TrFE) film, we fabricated flexible film bulk acoustic resonators (FBARs) which exhibit high sharp resonance peaks. The pressure sensor was made by sandwiching the FBARs with two PDMS microneedle patches. Heartbeat and respiration rate monitoring were achieved using the pressure sensor. This work demonstrates the feasibility of high-performance flexible piezoelectric acoustic resonators based on low-porosity P(VDF-TrFE) films, which could see wider applications in the wearable sensors for both physical and chemical sensing.

Sandwich Biomimetic Scaffold Based Tendon Stem/Progenitor Cell Alignment in a 3D Microenvironment for Functional Tendon Regeneration.

Tendon injuries are some of the most commonly diagnosed musculoskeletal diseases. Tendon regeneration is sensitive to the topology of the substitute as it affects the cellular microenvironment and homeostasis. To bionic in vivo three-dimensional (3D) aligned microenvironment, an ordered 3D sandwich model was used to investigate the cell response in the tendon. First, high-resolution 3D printing provided parallel-grooved topographical cues on the hydrogel surface. Then the cells were seeded on its surface to acquire a 2D model. Afterward, an additional hydrogel coating layer was applied to the cells to create the 3D model. The interaction between cells and order structures in three-dimensions is yet to be explored. The study found that the tendon stem/progenitor cells (TSPCs) still maintain their ordering growth in the 3D model as in the 2D model. The study also found that the 3D-aligned TSPCs exhibited enhanced tenogenic differentiation through the PI3K-AKT signaling pathway and presented a less inflammatory phenotype than those in the 2D model. The in vivo implantation of such a 3D-aligned TSPC composite promoted tendon regeneration and mitigated heterotopic ossification in an Achilles defect model. These findings demonstrated that 3D-aligned TSPCs within a biomimetic topology environment are promising for functional tendon regeneration.

Multimodal Electrocorticogram Active Electrode Array Based on Zinc Oxide-Thin Film Transistors.

Active electrocorticogram (ECoG) electrodes can amplify weak electrophysiological signals and improve anti-interference ability; however, traditional active electrodes are opaque and cannot realize photoelectric collaborative observation. In this study, an active and fully transparent ECoG array based on zinc oxide thin-film transistors (ZnO TFTs) is developed as a local neural signal amplifier for electrophysiological monitoring. The transparency of the proposed ECoG array is up to 85%, which is superior to that of the previously reported active electrode arrays. Various electrical characterizations have demonstrated its ability to record electrophysiological signals with a higher signal-to-noise ratio of 19.9 dB compared to the Au grid (13.2 dB). The high transparency of the ZnO-TFT electrode array allows the concurrent collection of high-quality electrophysiological signals (32.2 dB) under direct optical stimulation of the optogenetic mice brain. The ECoG array can also work under 7-Tesla magnetic resonance imaging to record local brain signals without affecting brain tissue imaging. As the most transparent active ECoG array to date, it provides a powerful multimodal tool for brain observation, including recording brain activity under synchronized optical modulation and 7-Tesla magnetic resonance imaging.

Experimental study on single biomolecule sensing using MoS2-graphene heterostructure nanopores.

Solid-state nanopores play an important role in sensing single-biomolecules such as DNA and proteins. However, an ultra-short translocation time hinders nanopores from acquiring more detailed information about biomolecules, and further applications such as sequencing and molecular structure analysis are limited. Related studies have shown that MoS2 has no obvious impediment to biomolecule translocation while graphene may cause obstacles to this process. By combining these two-dimensional materials, nanopores might slow the biomolecule passage. Herein, we fabricated sub-10 nm ultra-thin MoS2-graphene heterostructure nanopores with high stability and tested both dsDNA and native protein (BSA) at the single-molecule level in experiments for the first time. Some special signals with advanced order are observed, which may reflect the shape change of the BSA molecules during the slow translocation process. The results show that the translocation time of BSA is slowed down up to more than 100 ms and the signal length and form are determined by the extent of interaction between the BSA and the heterostructure nanopore. The weak interaction between the BSA and the MoS2 layer increases the translocation probability, and meanwhile, the strong interaction of the graphene layer to BSA slows down the translocation and changes its structure. Therefore, our findings indicate the possibilities of slowing down the single-biomolecule translocation and the capability of acquiring more detailed information about biomolecules using MoS2-graphene heterostructure nanopores.

The 3.4 GHz BAW RF Filter Based on Single Crystal AlN Resonator for 5G Application.

To meet the stringent requirements of 5G communication, we proposed a high-performance bulk acoustic wave (BAW) filter based on single crystal AlN piezoelectric films on a SiC substrate. The fabrication of the BAW filter is compatible with the GaN high electron mobility transistor (HEMT) process, enabling the implementation of the integration of the BAW device and high-performance monolithic microwave integrated circuit (MMIC). The single crystal AlN piezoelectric film with 650-nm thickness was epitaxially grown on the SiC substrate by Metal Organic Chemical Vapor Deposition (MOCVD). After wafer bonding and substrate removal, the single crystal AlN film with electrode layers was transferred to another SiC wafer to form an air gap type BAW. Testing results showed that the fabricated resonators have a maximum Q-factor up to 837 at 3.3 GHz resonant frequency and electromechanical coupling coefficient up to 7.2%. Ladder-type filters were developed to verify the capabilities of the BAW and process, which has a center frequency of 3.38 GHz with 160 MHz 3 dB bandwidth. The filter achieved a minimum 1.5 dB insertion loss and more than 31 dB out-of-band rejection. The high performance of the filters is attributed to the high crystallinity and low defects of epitaxial single crystal AlN films.

Coexistence of Contact Electrification and Dynamic p-n Junction Modulation Effects in Triboelectrification.

The triboelectric effect occurs when two dissimilar materials are in physical contact, attributed to the combination of contact electrification (CE) and electrostatic induction. It has been extensively explored for the development of high-performance triboelectric nanogenerators (TENGs). In this paper, we report on, besides the CE-related charge generation, an additional charge generation phenomenon associated with the modulation of the p-n junction when two semiconductor materials [methylammonium lead iodide (MAPI) and poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS)] are put in contact and separated dynamically. The electrical outputs generated by the CE effect are determined by the surface potential difference between the two friction materials, while the ones induced by the p-n junction modulation are determined by the dynamic variations in the depletion widths of the two semiconductor friction materials. The outputs generated by the CE effect and the p-n junction effect are well separated in time scale; the p-n junction modulation contributes ∼20% of the total charge generated and could be varied by changing the chemical composition of the semiconductors. The results may provide an alternative method for the development of high-performance TENGs by utilizing this additional p-n junction modulation effect.

Monolithically integrated microchannel plate functionalized with ZnO nanorods for fluorescence-enhanced digital polymerase chain reaction.

In this paper, we report on an integrated microfluidic digital PCR system for rapid and high-performance absolute quantification of DNA at a single-molecular level. Microchannel plate (MCP), a highly porous glass membrane conventionally used as a particle multiplier in detectors, is demonstrated here as an ideal platform for the sample partition and high-fidelity DNA detection. The density of the microreactors reaches up to 1563 mm-2, with a total number of 25,000 chambers each in 100 pL volumes embedded in 4 × 4 mm2 MCP. This glass membrane consisting of highly-regular, densely-packed and high-aspect ratio microchannels is batch-fabricated through fiber-draw technology that requires no cumbersome lithography or etching process. The sidewalls, having a slight tilting angle with respect to the surface normal, can be functionalized with ZnO nanorods through one-step shadowing-based deposition without resorting to complicated solution-process or lithography. In this way, the required thermal cycling time for end-point detection has been reduced from 40 min to 25 min through plasmonic fluorescence enhancement compared to bare MCP without nanostructures. The digital PCR performance of our system has been validated by using bacteriophage λDNA and PLAU genes. The dynamic range achieved is noted as 105 ranging from 1 × 103 to 1 × 107 copies/µL and the measurement deviation is less than 5%. The detection limit is determined to be 1.4 copies/µL. The density of microchambers could be easily scaled for extensive applications and detection ranges by fabricating various MCP matrix structures. Given this high performance and a straightforward fabrication process of MCP, the device is expected to replace conventional PCR equipment for high fidelity and wide dynamic range single-molecule counting.