A portable transistor immunosensor for fast identification of porcine epidemic diarrhea virus.

Widespread distribution of porcine epidemic diarrhea virus (PEDV) has led to catastrophic losses to the global pig farming industry. As a result, there is an urgent need for rapid, sensitive and accurate tests for PEDV to enable timely and effective interventions. In the present study, we develop and validate a floating gate carbon nanotubes field-effect transistor (FG CNT-FET)-based portable immunosensor for rapid identification of PEDV in a sensitive and accurate manner. To improve the affinity, a unique PEDV spike protein-specific monoclonal antibody is prepared by purification, and subsequently modified on FG CNT-FET sensor to recognize PEDV. The developed FET biosensor enables highly sensitive detection (LoD: 8.1 fg/mL and 100.14 TCID50/mL for recombinant spike proteins and PEDV, respectively), as well as satisfactory specificity. Notably, an integrated portable platform consisting of a pluggable FG CNT-FET chip and a portable device can discriminate PEDV positive from negative samples and even identify PEDV and porcine deltacoronavirus within 1 min with 100% accuracy. The portable sensing platform offers the capability to quickly, sensitively and accurately identify PEDV, which further points to a possibility of point of care (POC) applications of large-scale surveillance in pig breeding facilities.

Surface Lattice Modulation Enables Stable Cycling of High-Loading All-solid-state Batteries at High Voltages.

Halide solid electrolytes, known for their high ionic conductivity at room temperature and good oxidative stability, face notable challenges in all-solid-state Li-ion batteries (ASSBs), especially with unstable cathode/solid electrolyte (SE) interface and increasing interfacial resistance during cycling. In this work, we have developed an Al3+-doped, cation-disordered epitaxial nanolayer on the LiCoO2 surface by reacting it with an artificially constructed AlPO4 nanoshell; this lithium-deficient layer featuring a rock-salt-like phase effectively suppresses oxidative decomposition of Li3InCl6 electrolyte and stabilizes the cathode/SE interface at 4.5 V. The ASSBs with the halide electrolyte Li3InCl6 and a high-loading LiCoO2 cathode demonstrated high discharge capacity and long cycling life from 3 to 4.5 V. Our findings emphasize the importance of specialized cathode surface modification in preventing SE degradation and achieving stable cycling of halide-based ASSBs at high voltages.

Acupuncture Needle-Based Transistor Neuroprobe for In Vivo Monitoring of Neurotransmitter.

Chemical communication via neurotransmitters is central to brain functions. Nevertheless, in vivo real-time monitoring of neurotransmitters released in the brain, especially the electrochemically inactive molecules, remains a great challenge. In this work, a novel needle field-effect transistor (FET) microsensor based on an acupuncture needle is proposed, which is demonstrated to be capable of real-time monitoring dopamine molecules as well as neuropeptide Y in vivo. The FET microstructure is fabricated by successively wrapping an insulating layer and a gold layer on the top of the needle, where the needle and the Au served as the source and drain, respectively. After assembling reduced graphene oxide (RGO) between the source and drain electrodes, the specific aptamer is immobilized on the RGO, making this needle-FET biosensor highly selective and sensitive to real-time monitor neurotransmitters released from rat brain, even in a Parkinson's diseases model. Furthermore, the needle-FET biosensor is applied to detect a variety of targets including hormones, proteins, and nucleic acid. By constructing a FET sensing interface on an acupuncture needle and implanting the sensor in a rat's brain for in vivo detection, this work provides a new sight in the FET domain and further expands the species of real-time in vivo detection.

Receptor-Mediated Field Effect Transistor Biosensor for Real-Time Monitoring of Glutamate Release from Primary Hippocampal Neurons.

Glutamate, one of the most important central excitatory neurotransmitters, plays crucial roles in nerve signal transduction and is implicated in several neurological disorders. However, no effective means has been developed for specific detection of glutamate released from primary cultured neurons. Here we present a reduced graphene oxide (RGO)-based field effect transistor (FET) biosensor functionalized with synthesized glutamate receptor for real-time monitoring of glutamate release from primary cultured rat hippocampus neurons. Metabotropic glutamate receptors (mGluR) was specifically synthesized and then immobilized on the RGO surface by 1-pyrenebutanoic acid succinimidyl ester (PASE) linker, after which target glutamate (pI = 3.22) could specifically bind to the synthesized mGluR in the neutral buffer, causing the charge density change. After the neurons were cultured on the sensing channel with a self-made liquid reservoir, the FET biosensor could discriminate glutamate in the femtomolar range in complete cell culture medium and generate encouraging results in real-time monitoring of glutamate release from primary rat hippocampus neurons. This work is the first report of specific and direct detection of glutamate molecules released from primary culture of differentiated central neurons, which may further help understand the nature of neuronal communication. Moreover, this work paves a way for the detection of electrochemically inactive small molecules released by cells.

Electrical and Label-Free Quantification of Exosomes with a Reduced Graphene Oxide Field Effect Transistor Biosensor.

Exosomes are small membrane-bound nanovesicles with a size of 50-150 nm which contain many functional biomolecules, such as nucleic acids and proteins. Due to their high homology with parental generation, they are of great significance in clinical diagnosis. At present, the quantitative detection of low concentrations of cancer-derived exosomes present in biofluids is still a great challenge. In this study, we develop an electrical and label-free method to directly detect exosomes with high sensitivity based on a reduced graphene oxide (RGO) field effect transistor (FET) biosensor. An RGO FET biosensor modified with specific antibody CD63 in the sensing area was fabricated and was used for electrical and label-free quantification of exosomes. The method achieved a low limit of detection down to 33 particles/µL, which is lower than that of many other available methods. In addition, the FET biosensor was employed to detect exosomes in clinical serum samples, showing significant differences in detecting healthy people and prostate cancer (PCa) patients. Different from other technologies, this study provides a unique technology capable of directly quantifying exosomes without labeling, indicating its potential as a tool for early diagnosis of cancer.

A field effect transistor modified with reduced graphene oxide for immunodetection of Ebola virus.

The authors describe a field effect transistor (FET) based immunoassay for the detection of inactivated ebola virus (EBOV). An equine antibody against the EBOV glycoprotein was immobilized on the surface of the FET that was previously modified with reduced graphene oxide (RGO). The antibody against EBOV was immobilized on the modified FET, and the response to EBOV was measured as a function of the shift of Dirac voltage. The method can detect the EBOV over the concentration range from 2.4 × 10-12 g·mL-1 to 1.2 × 10-7 g·mL-1 and with a limit of detection as low as 2.4 pg·mL-1. The assay has satisfactory specificity and was applied to the quantitation of inactivated EBOV in spiked serum. Graphical abstract Schematic presentation of the field effect transistor (FET) modified with reduced graphene oxide (RGO) for Ebola Virus (EBOV) detection. Specific binding between EBOV and the anti-EBOV antibody (Ab) on the FET device leads to obvious current change.

Monitoring of pH changes in a live rat brain with MoS2/PAN functionalized microneedles.

Monitoring the dynamic pH changes in vivo remains very essential to comprehend the function of pH in various physiological processes. In this study, we report a high-performance electrochemical pH microneedle based on an acupuncture needle (AN) for real-time monitoring of pH changes in a rat brain. The pH microneedle was prepared by a layer-to-layer assembly of molybdenum disulfide (MoS2) nanosheets and polyaniline (PAN), with an attempt to achieve a highly sensitive detection of hydrogen ions (H+). The as-prepared PAN/MoS2/AN exhibited a high Nernstian response of -51.2 mV per pH over a wide pH range from 3.0 to 9.0, and excellent selectivity toward pH against other potential interfering species in the brain. Moreover, the corresponding open circuit potential rapidly increased and decreased when Na2CO3 or NaH2PO4 was injected into the rat brain, respectively, demonstrating that the PAN/MoS2/AN has an excellent response toward pH changes in vivo. This work provides a new potentiometric method for real-time monitoring of dynamic pH changes in vivo with high reliability and stability.

A Review on Bacteriorhodopsin-Based Bioelectronic Devices.

Bacteriorhodopsin protein extracted from Halobacterium salinarum is widely used in many biohybrid electronic devices and forms a research subject known as bioelectronics, which merges biology with electronic technique. The specific molecule structure and components of bR lead to its unique photocycle characteristic, which consists of several intermediates (bR, K, L, M, N, and O) and results in proton pump function. In this review, working principles and properties of bacteriorhodopsin are briefly introduced, as well as bR layer preparation method. After that, different bR-based devices divided into photochemical and photoelectric applications are shown. Finally, outlook and conclusions are drawn to inspire new design of high-performance bR-based biohybrid electronic devices.

A surface acoustic wave biosensor synergizing DNA-mediated in situ silver nanoparticle growth for a highly specific and signal-amplified nucleic acid assay.

This work reports a surface acoustic wave (SAW) DNA sensor that synergizes the surface mass effect for signal-amplified and sequence-specific DNA detection in blood serum. By combining an enzyme-mediated DNA extension reaction (both viscoelastic and mass fractions) with the in situ synthesis of silver nanoparticles (mass fraction), a highly sensitive SAW biosensing interface with synergistic mass loading was tailor-engineered. As target DNA hybridized with the surface-confined capture probes, the exposed 3'-OH terminal of the target sequence could be triggered to elongate in the presence of terminal deoxynucleoside transferase (TdT) and deoxy-ribonucleoside triphosphate (dNTP), thereby producing an evident mass effect. Importantly, the extended domain can serve as a template to specifically hybridize with Ag+-binding sequences. In the presence of reducing agents, the accumulated silver ions would nucleate for the in situ synthesis of silver nanoparticles, further enhancing the mass loading. By using this approach, we observed a rapid growth event of silver nanoparticles for signal enhancement, which improved the detection limit (0.8 pM) of the SAW sensor by 3 orders of magnitude as compared to the strategy without signal amplification (at the nanomolar level). The sensor also achieved a high specificity in discriminating even a single-mismatched DNA sequence, and meanwhile could probe the low-abundance DNA molecules directly in human serum with minimal interference. These advantages make the SAW biosensor promising for practical applications, such as monitoring of molecular interactions and disease diagnostics.

MoS2/Pt nanocomposite-functionalized microneedle for real-time monitoring of hydrogen peroxide release from living cells.

This work describes the adaptive use of a conventional stainless steel acupuncture needle as the electrode substrate for construction of a molybdenum disulfide (MoS2) and platinum nanoparticles (PtNPs) layer-modified microneedle sensor for real-time monitoring of hydrogen peroxide (H2O2) release from living cells. To construct the nanocomposite-functionalized microneedle, the needle surface was first coated with a gold film by ion sputtering to enhance the conductivity. Subsequently, an electrochemical deposition method was successfully employed to deposit MoS2 nanosheet and Pt nanoparticles on the needle tip as the sensing interface. Electrochemical study demonstrated that the MoS2/PtNPs nanocomposite-modified needle exhibited excellent catalytic performance and low over-potential toward the reduction of H2O2. Not only did the microneedle achieve a wide linear range from 1 to 100 µmol L-1 with a limit of detection down to 0.686 µmol L-1, but it also realized the highly specific detection of H2O2. Owing to these remarkable analytical advantages, the prepared microneedle was applied to determine H2O2 release from living cells with satisfactory results. The MoS2/PtNPs nanocomposite-functionalized microneedle sensor is simple and affordable, and can serve as a promising electrochemical nonenzymatic sensing platform. Moreover, this superfine needle sensor shows great potential for real-time monitoring of reactive oxygen species in vivo with minimal damage.

Photocatalysis-Induced Renewable Field-Effect Transistor for Protein Detection.

The field-effect transistor (FET) biosensor has attracted extensive attentions, due to its unique features in detecting various biomolecules with high sensitivity and selectivity. However, currently used FET biosensors obtaining from expensive and elaborate micro/nanofabrication are always disposable because the analyte cannot be efficiently removed after detection. In this work, we established a photocatalysis-induced renewable graphene-FET (G-FET) biosensor for protein detection, by layer-to-layer assembling reduced graphene oxide (RGO) and RGO-encapsulated TiO2 composites to form a sandwiching RGO@TiO2 structure on a prefabricated FET sensor surface. After immobilization of anti-D-Dimer on the graphene surface, sensitive detection of D-Dimer was achieved with the detection limits of 10 pg/mL in PBS and 100 pg/mL in serum, respectively. Notably, renewal of the FET biosensor for recycling measurements was significantly realized by photocatalytically cleaning the substances on the graphene surface. This work demonstrates for the first time the development and application of photocatalytically renewable G-FET biosensor, paving a new way for G-FET sensor toward a plethora of diverse applications.

Real-Time Monitoring of Nitric Oxide at Single-Cell Level with Porphyrin-Functionalized Graphene Field-Effect Transistor Biosensor.

An ultrasensitive and highly efficient assay for real-time monitoring of nitric oxide (NO) at single-cell level based on a reduced graphene oxide (RGO) and iron-porphyrin-functionalized graphene (FGPCs) field-effect transistor (FET) biosensor is reported. A layer-to-layer assembly of RGO and FGPCs on a prefabricated FET sensor surface through π-π stacking interaction allowed superior electrical conductivity caused by RGO, and highly catalytic specificity induced by metalloporphyrin, ensuring the ultrasensitive and highly specific detection of NO. The results demonstrated that the RGO/FGPCs FET biosensor was capable of real-time monitoring of NO in the range from 1 pM to 100 nM with the limit of detection as low as 1 pM in phosphate-buffered saline (PBS) and 10 pM in the cell medium, respectively. Moreover, the developed biosensor could be used for real-time monitoring of NO released from human umbilical vein endothelial cells (HUVECs) at single-cell level. Along with its miniaturized sizes, ultrasensitive characteristics, and fast response, the FET biosensor is promising as a new platform for potential biological and diagnostic applications.

[Analysis of 105 Incarcerated Inmate's Death].

OBJECTIVE: To analyze the characteristics in the incarcerated inmate's death, investigate the main cause of death of the incarcerated inmate and provide some information for forensic investigation. METHODS: The cases from the forensic medical center of Shanxi Medical University from 2005 to 2013 were selected. The statistical analysis was performed by using the incarcerated inmate's gender, age, cause of death, manner of death, and disease as the markers. RESULTS: There were 100 men, 5 women in the 105 incarcerated inmates; the age range was from 16 to 65 years; Inmates were mostly died of natural diseases, mainly in the respiratory and cardiovascular diseases; the main unnatural death was suicide with a rate of 54.5%. CONCLUSION: At present, most incarcerated inmate's death are due to natural diseases. The prison should improve incarcerated inmate's lives, work and health care conditions, and strengthen supervision of law enforcement.

Photocatalytically Renewable Micro-electrochemical Sensor for Real-Time Monitoring of Cells.

Electrode fouling and passivation is a substantial and inevitable limitation in electrochemical biosensing, and it is a great challenge to efficiently remove the contaminant without changing the surface structure and electrochemical performance. Herein, we propose a versatile and efficient strategy based on photocatalytic cleaning to construct renewable electrochemical sensors for cell analysis. This kind of sensor was fabricated by controllable assembly of reduced graphene oxide (RGO) and TiO2 to form a sandwiching RGO@TiO2 structure, followed by deposition of Au nanoparticles (NPs) onto the RGO shell. The Au NPs-RGO composite shell provides high electrochemical performance. Meanwhile, the encapsulated TiO2 ensures an excellent photocatalytic cleaning property. Application of this renewable microsensor for detection of nitric oxide (NO) release from cells demonstrates the great potential of this strategy in electrode regeneration and biosensing.

Real-time Monitoring of Discrete Synaptic Release Events and Excitatory Potentials within Self-reconstructed Neuromuscular Junctions.

Chemical synaptic transmission is central to the brain functions. In this regard, real-time monitoring of chemical synaptic transmission during neuronal communication remains a great challenge. In this work, in vivo-like oriented neural networks between superior cervical ganglion (SCG) neurons and their effector smooth muscle cells (SMC) were assembled in a microfluidic device. This allowed amperometric detection of individual neurotransmitter release events inside functional SCG-SMC synapse with carbon fiber nanoelectrodes as well as recording of postsynaptic potential using glass nanopipette electrodes. The high vesicular release activities essentially involved complex events arising from flickering fusion pores as quantitatively established based on simulations. This work allowed for the first time monitoring in situ chemical synaptic transmission under conditions close to those found in vivo, which may yield important and new insights into the nature of neuronal communications.

Nanoelectrode for amperometric monitoring of individual vesicular exocytosis inside single synapses.

Chemical neurotransmission occurs at chemical synapses and endocrine glands, but up to now there was no means for direct monitoring of neurotransmitter exocytosis fluxes and their precise kinetics from inside an individual synapse. The fabrication of a novel finite conical nanoelectrode is reported perfectly suited in size and electrochemical properties for probing amperometrically inside what appears to be single synapses and monitoring individual vesicular exocytotic events in real time. This allowed obtaining direct and important physiological evidences which may yield important and new insights into the nature of synaptic communications.

Adult-onset congenital intestinal malrotation: A case report and literature review.

BACKGROUND: Intestinal malrotation is an infrequent congenital anomaly primarily observed in neonates, and adult-onset cases are exceedingly rare. Studies on adult congenital intestinal malrotation are limited. METHODS: A case with congenital intestinal malrotation is reported in our study. The clinical data were collected and the treatment process and effect were evaluated. RESULTS: A 45-year-old female who had been experiencing vomiting for over 40 years was admitted to our hospital. According to the result of CT scan, intestinal volvulus accompanied by bowel obstruction was suspected. Then laparoscopic examination was applied to the patient and was ultimately diagnosed with adult congenital intestinal malrotation. We performed Ladd's procedure combined with gastrojejunostomy and Braun anastomosis. The patient recovered well and was successfully discharged from the hospital on the 13th day after surgery. After a 6-month follow-up, the symptom of vomiting was significantly alleviated and body weight was gained for 10 kg. She was very satisfied with the treatment. CONCLUSION: Adult congenital intestinal malrotation is a rare disease that is often misdiagnosed owing to nonspecific clinical manifestations. Therefore, awareness about this condition should be enhanced. Surgery remains the cornerstone of treatment for this disease. Combining gastrojejunostomy and Braun anastomosis with the traditional Ladd procedure can optimize surgical outcomes.

Integrated Microfluidic-Transistor Sensing System for Multiplexed Detection of Traumatic Brain Injury Biomarkers.

Traumatic brain injury (TBI) is widely recognized as a global public health crisis, affecting millions of people each year, leading to permanent neurologic, emotional, and occupational disability, and highlighting the urgent need for rapid, sensitive, and early assessment. Here, we design a novel and simple lithography-free method for preparing dual-channel graphene-based field-effect transistors (G-FETs) and integrating them with microfluidic channels for simultaneously multiplexed detection of key blood TBI biomarkers: neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP). The G-FET utilizes an ingenious dual-channel electrode array design, where the source is shared between channels and the drains are independent of each other, which is the key to achieving simultaneous output of dual detection signals. At the same time, the microfluidic chip realizes microscale fluidic control and fast sample response time. This integrated detection system shows excellent sensitivity in biological fluids for the TBI biomarkers with detection limits as low as 55.63 fg/mL for NFL and 144.45 fg/mL for GFAP in phosphate-buffered saline (PBS) buffer, respectively. Finally, the clinical sample analysis shows promising performance for TBI detection, with an area under the curve (AUC) of 0.98 for the two biomarkers. And the combined dual-protein assay is also a good predictor of intracranial injury findings on computed tomography (CT) scans (AUC = 0.907). The integrated microfluidic G-FET device with a dual-signal output strategy has important potential for application in clinical practice, providing more comprehensive information for brain injury assessment.

Plug-and-play smart transistor bio-chips implementing point-of-care diagnosis of AMI with modified CRISPR/Cas12a system.

The point-of-care diagnosis of acute myocardial infarction (AMI), an extremely lethal disease with only a few hours of golden rescue time, is significant and urgently required. Here, we describe a plug-and-play carbon nanotube field effect transistor (CNT-FET) bio-chip supported with a smart portable readout for ultrasensitive and on-site testing of cardiac troponin I (cTnI), which is one of the most specific and valuable biomarkers of AMI. A modified clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a system, featuring the G-triplex structured reporter, was first combined with the CNT-FET to realize non-nucleic acid detection. Such a unique CNT-FET biosensor achieved the high sensitivity (LOD: 0.33 fg/mL), which is expected to give timely warning in the early stage of myocardial injury. In addition, a bilayer gate dielectric consisting of Y2O3/HfO2, employed into the passivation process, enabled the high environmental stability and repeatability of CNT-FET. More importantly, the homemade compact chip readout forged a field-deployable cTnI analytical tool, realizing "plasma-to-answer" performance for AMI patients in point-of-care testing scenarios. The developed technology holds promise to help doctors make clinical decisions faster, especially in remote areas.

Simultaneous generation of gradients with gradually changed slope in a microfluidic device for quantifying axon response.

Over the past decades, various microfluidic devices have been developed to investigate the role of the molecular gradient in axonal development; however, there are very few devices providing quantitative information about the response of axons to molecular gradients with different slopes. Here, we propose a novel laminar-based microfluidic device enabling simultaneous generation of multiple gradients with gradually changed slope on a single chip. This device, with two asymmetrically designed peripheral channels and opposite flow direction, could generate gradients with gradually changed slope in the center channel, enabling us to investigate simultaneously the response of axons to multiple slope gradients with the same batch of neurons. We quantitatively investigated the response of axon growth rate and growth direction to substrate-bound laminin gradients with different slopes using this single-layer chip. Furthermore, we compartmented this gradient generation chip and a cell culture chip by a porous membrane to investigate quantitatively the response of axon growth rate to the gradient of soluble factor netrin-1. The results suggested that contacting with a molecular gradient would effectively accelerate neurites growth and enhance axonal formation, and the axon guidance ratio obviously increased with the increase of gradient slope in a proper range. The capability of generating a molecular gradient with continuously variable slopes on a single chip would open up opportunities for obtaining quantitative information about the sensitivity of axons and other types of cells in response to gradients of various proteins.