Optogenetic neuromuscular actuation of a miniature electronic biohybrid robot.

Neuronal control of skeletal muscle function is ubiquitous across species for locomotion and doing work. In particular, emergent behaviors of neurons in biohybrid neuromuscular systems can advance bioinspired locomotion research. Although recent studies have demonstrated that chemical or optogenetic stimulation of neurons can control muscular actuation through the neuromuscular junction (NMJ), the correlation between neuronal activities and resulting modulation in the muscle responses is less understood, hindering the engineering of high-level functional biohybrid systems.

Extension Doping with Low-Resistance Contacts for P-Type Monolayer WSe Field-Effect Transistors.

Source/Drain extension doping is crucial for minimizing the series resistance of the ungated channel and reducing the contact resistance of field-effect transistors (FETs) in complementary metal-oxide-semiconductor (CMOS) technology. 2D semiconductors, such as MoS and WSe, are promising channel materials for beyond-silicon CMOS. A key challenge is to achieve extension doping for 2D monolayer FETs without damaging the atomically thin material.

Detecting DNA translocation through a nanopore using a van der Waals heterojunction diode.

A long-unrealized goal in solid-state nanopore sensing is to achieve out-of-plane electrical sensing and control of DNA during translocation, which is a prerequisite for base-by-base ratcheting that enables DNA sequencing in biological nanopores. Two-dimensional (2D) heterostructures, with their capability to construct out-of-plane electronics with atomic layer precision, are ideal yet unexplored candidates for use as electrical sensing membranes. Here, we demonstrate a nanopore architecture using a vertical 2D heterojunction diode consisting of p-type WSe on n-type MoS.

Review on biphasic blood drying method for rapid pathogen detection in bloodstream infections.

Rapid and accurate detection of pathogenic microorganisms in blood is critical for diagnosing life-threatening conditions such as bloodstream infections (BSIs). Current methods for the detection and identification of bacteria from large volumes of blood (5 mL) involve culture steps followed by DNA extraction/purification/concentration and Polymerase Chain Reaction (PCR)-based nucleic acid amplification. DNA extraction and amplification directly from blood samples is hampered by the complexity of the blood matrix, resulting in time-consuming and labor-intensive processes.

Amplification-free, OR-gated CRISPR-Cascade reaction for pathogen detection in blood samples.

Rapid and accurate detection of DNA from disease-causing pathogens is essential for controlling the spread of infections and administering timely treatments. While traditional molecular diagnostics techniques like PCR are highly sensitive, they include nucleic acid amplification and many need to be performed in centralized laboratories, limiting their utility in point-of-care settings. Recent advances in CRISPR-based diagnostics (CRISPR-Dx) have demonstrated the potential for highly specific molecular detection, but the sensitivity is often constrained by the slow trans-cleavage activity of Cas enzymes, necessitating preamplification of target nucleic acids.

Detecting DNA Translocation through a Nanopore using a van der Waals Heterojunction Diode.

A long-unrealized goal in solid-state nanopore sensing is to achieve out-of-plane electrical sensing and control of DNA during translocation, which is a prerequisite for base-by-base ratcheting that enables DNA sequencing in biological nanopores. Two-dimensional (2D) heterostructures, with their capability to construct out-of-plane electronics with atomic layer precision, are ideal yet unexplored candidates for use as electrical sensing membranes. Here we demonstrate a nanopore architecture using a vertical 2D heterojunction diode consisting of p-type WSe on n-type MoS.

On the design and fabrication of nanoliter-volume hanging drop networks.

Hanging drop cultures provide a favorable environment for the gentle, gel-free formation of highly uniform three-dimensional cell cultures often used in drug screening applications. Initial cell numbers can be limited, as with primary cells provided by minimally invasive biopsies. Therefore, it can be beneficial to divide cells into miniaturized arrays of hanging drops to supply a larger number of samples.

1-Octanol-assisted ultra-small volume droplet microfluidics with nanoelectrospray ionization mass spectrometry.

Background: Droplet microfluidics with push-pull and microdialysis sampling from brain slices, cultured cells and engineered tissues produce low volume mass limited samples containing analytes sampled from the extracellular space. This sampling approach coupled to mass spectrometry (MS) detection allows evaluation of time-dependent chemical changes. Our goal is an approach for continuous sampling and segregation of extracellular samples into picoliter droplets followed by the characterization of the droplets using nanoelectrospray ionization (nESI) MS.

Point-of-Care Multiplex Detection of Respiratory Viruses.

The COVID-19 pandemic, in addition to the co-occurrence of influenza virus and respiratory syncytial virus (RSV), has emphasized the requirement for efficient and reliable multiplex diagnostic methods for respiratory infections. While existing multiplex detection techniques are based on reverse transcription quantitative polymerase chain reaction (RT-qPCR) and extraction and purification kits, the need for complex instrumentation and elevated cost limit their scalability and availability. In this study, we have developed a point-of-care (POC) device based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) that can simultaneously detect four respiratory viruses (SARS-CoV-2, Influenza A, Influenza B, and RSV) and perform two controls in less than 30 min, while avoiding the use of the RNA extraction kit.

Dried Blood Matrix as a New Material for the Detection of DNA Viruses.

The gold standard for diagnosing viruses such as the Hepatitis B Virus has remained largely unchanged, relying on conventional methods involving extraction, purification, and polymerase chain reaction (PCR). This approach is hindered by limited availability, as it is time-consuming and requires highly trained personnel. Moreover, it suffers from low recovery rates of the nucleic acid molecules for samples with low copy numbers.

Edge-Passivated Monolayer WSe Nanoribbon Transistors.

The ongoing reduction in transistor sizes drives advancements in information technology. However, as transistors shrink to the nanometer scale, surface and edge states begin to constrain their performance. 2D semiconductors like transition metal dichalcogenides (TMDs) have dangling-bond-free surfaces, hence achieving minimal surface states.

Leucyl-tRNA Synthetase Contributes to Muscle Weakness through Mammalian Target of Rapamycin Complex 1 Activation and Autophagy Suppression in a Mouse Model of Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD), caused by loss-of-function mutations in the dystrophin gene, results in progressive muscle weakness and early fatality. Impaired autophagy is one of the cellular hallmarks of DMD, contributing to the disease progression. Molecular mechanisms underlying the inhibition of autophagy in DMD are not well understood.

Comparing fabrication techniques for engineered cardiac tissue.

Tissue engineering can provide in vitro models for drug testing, disease modeling, and perhaps someday, tissue/organ replacements. For building 3D heart tissue, the alignment of cardiac cells or cardiomyocytes (CMs) is important in generating a synchronously contracting tissue. To that end, researchers have generated several fabrication methods for building heart tissue, but direct comparisons of pros and cons using the same cell source is lacking.

Neuronal innervation regulates the secretion of neurotrophic myokines and exosomes from skeletal muscle.

Myokines and exosomes, originating from skeletal muscle, are shown to play a significant role in maintaining brain homeostasis. While exercise has been reported to promote muscle secretion, little is known about the effects of neuronal innervation and activity on the yield and molecular composition of biologically active molecules from muscle. As neuromuscular diseases and disabilities associated with denervation impact muscle metabolism, we hypothesize that neuronal innervation and firing may play a pivotal role in regulating secretion activities of skeletal muscles.

Stereotactic radiotherapy: An educational narrative review.

Stereotactic radiotherapy is a term collectively used to describe the radiation treatment techniques that allow for the delivery of highly precise ionizing radiation. It is usually a high dose per session in single or few fractions. This treatment approach has been in medical use for over six decades and has primarily evolved in the last two decades.

Cellular subpopulations identified using an ensemble average of multiple dielectrophoresis measurements.

While the average value measurement approach can successfully analyze and predict the general behavior and biophysical properties of an isogenic cell population, it fails when significant differences among individual cells are generated in the population by intracellular changes such as the cell cycle, or different cellular responses to certain stimuli. Detecting such single-cell differences in a cell population has remained elusive. Here, we describe an easy-to-implement and generalizable platform that measures the dielectrophoretic cross-over frequency of individual cells by decreasing measurement noise with a stochastic method and computing ensemble average statistics.

Multiplexed electrical detection of whole viruses from plasma in a microfluidic platform.

The advancement of point-of-care diagnostics is crucial to improving patient outcomes, especially in areas with low access to hospitals or specialized laboratories. In particular, rapid, sensitive, and multiplexed detection of disease biomarkers has great potential to achieve accurate diagnosis and inform high quality care for patients. Our Coulter counting and immunocapture based detection system has previously shown its broad applicability in the detection of cells, proteins, and nucleic acids.

A Blood Drying Process for DNA Amplification.

The presence of numerous inhibitors in blood makes their use in nucleic acid amplification techniques difficult. Current methods for extracting and purifying pathogenic DNA from blood involve removal of inhibitors, resulting in low and inconsistent DNA recovery rates. To address this issue, a biphasic method is developed that simultaneously achieves inhibitor inactivation and DNA amplification without the need for a purification step.

Highly localized chemical sampling at sub-second temporal resolution enabled with a silicon nanodialysis platform at exceedingly slow flows.

Microdialysis (MD) is a versatile and powerful technique for chemical profiling of biological tissues and is widely used for quantification of neurotransmitters, neuropeptides, metabolites, biomarkers, and drugs in the central nervous system as well as in dermatology, ophthalmology, and in pain research. However, MD performance is severely limited by fundamental tradeoffs between chemical sensitivity, spatial resolution, and temporal response. Here, by using wafer-scale silicon microfabrication, we develop and demonstrate a nanodialysis (ND) sampling probe that enables highly localized chemical sampling with 100μm spatial resolution and sub-second temporal resolution at high recovery rates.

Targeting Duchenne muscular dystrophy by skipping DMD exon 45 with base editors.

Duchenne muscular dystrophy is an X-linked monogenic disease caused by mutations in the dystrophin gene () characterized by progressive muscle weakness, leading to loss of ambulation and decreased life expectancy. Since the current standard of care for Duchenne muscular dystrophy is to merely treat symptoms, there is a dire need for treatment modalities that can correct the underlying genetic mutations. While several gene replacement therapies are being explored in clinical trials, one emerging approach that can directly correct mutations in genomic DNA is base editing.

Advances in field-effect biosensors towards point-of-use.

The future of medical diagnostics calls for portable biosensors at the point of care, aiming to improve healthcare by reducing costs, improving access, and increasing quality-what is called the 'triple aim'. Developing point-of-care sensors that provide high sensitivity, detect multiple analytes, and provide real time measurements can expand access to medical diagnostics for all. Field-effect transistor (FET)-based biosensors have several advantages, including ultrahigh sensitivity, label-free and amplification-free detection, reduced cost and complexity, portability, and large-scale multiplexing.

Electrochemical point-of-care devices for the diagnosis of sepsis.

Sepsis is a life-threatening dysfunction of organ systems caused by a dysregulated immune system because of an infectious process. It remains one of the leading causes of hospital mortality and of hospital readmissions in the United States. Mortality from sepsis increases with each hour of delayed treatment, therefore, diagnostic devices that can reduce the time from the onset of a patient's infection to the delivery of appropriate therapy are urgently needed.

Cryopreservation Alters Tissue Structure and Improves Differentiation of Engineered Skeletal Muscle.

Tissue-engineered skeletal muscle can play an important role in regenerative medicine, disease modeling, drug testing, as well as the actuation of biohybrid machines. As the applications of engineered muscle tissues expand, there exists a growing need to cryopreserve and store these tissues without impairing function. In a previous study, we developed a cryopreservation protocol in which engineered skeletal muscle tissues are frozen before myogenic differentiation.

RhoA/ROCK signalling activated by ARHGEF3 promotes muscle weakness via autophagy in dystrophic mdx mice.

Background: Duchenne muscular dystrophy (DMD), caused by dystrophin deficiency, leads to progressive and fatal muscle weakness through yet-to-be-fully deciphered molecular perturbations. Emerging evidence implicates RhoA/Rho-associated protein kinase (ROCK) signalling in DMD pathology, yet its direct role in DMD muscle function, and related mechanisms, are unknown.

Methods: Three-dimensionally engineered dystrophin-deficient mdx skeletal muscles and mdx mice were used to test the role of ROCK in DMD muscle function in vitro and in situ, respectively.