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Many studies have shown that urokinase plasminogen activator (uPA) is causally involved in promoting cancer invasion and metastasis. Thus, monitoring uPA levels could be very useful in cancer diagnosis, identification of initial metastasis, and guiding cancer treatment. Here, the authors developed a novel and scalable uPA sensor based on a graphene-gold nanoparticle platform that uses fluorescence of quantum dots to rapidly (<1 h) detect uPA up to 100 pM. Indeed, the authors' sensor is highly selective and showed an ability to sense up to 100 pM uPA even in the presence of complex biological milieu such as the fetal bovine serum.

Point-of-care (POC) detection and diagnostic platforms provide critical information about health and safety conditions in austere and resource-limited settings in which medical, military, and disaster relief operations are conducted. In this work, low-cost paper materials commonly used in POC devices are coated with liquid-infused polymer surfaces and folded to produce geometries that precisely localize complex liquid samples undergoing concentration by evaporation. Liquid-infused polymer surfaces were fabricated by infusing silicone-coated paper with a chemically compatible polydimethylsiloxane oil to create a liquid overlayer. Tests on these surfaces showed no remaining bacterial cells after exposure to a sliding droplet containing a concentrated solution of Escherichia coli or Staphylococcus aureus, while samples without a liquid layer showed adhesion of both microdroplets and individual bacterial cells. Folding of the paper substrates with liquid-infused polymer surfaces into several functional 3D geometries enabled a clean separation and simultaneous concentration of a liquid containing rhodamine dye into discrete, predefined locations. When used with bacteria, which are known for their ability to adhere to nearly any surface type, functional geometries with liquid-infused polymer surfaces concentrated the cells at levels significantly higher than geometries with dry control surfaces. These results show the potential of synergistically combining paper-based materials with liquid-infused polymer surfaces for the manipulation and handling of complex samples, which may help the future engineering of POC devices.

Today, the area of point-of-care diagnostics is synonymous with paper microfluidics where cheap, disposable, and on-the-spot detection toolkits are being developed for a variety of chemical tests. In this work, we present a novel application of microfluidic paper-based analytical devices (μPADs) to study the behavior of a small model nematode, Caenorhabditis elegans. We describe schemes of μPAD fabrication on paper and plastic substrates where membranes are created in agarose and Pluronic gel. Methods are demonstrated for loading, visualizing, and transferring single and multiple nematodes. Using an anthelmintic drug, levamisole, we show that chemical testing on C. elegans is easily performed because of the open device structure. A custom program is written to automatically recognize individual worms on the μPADs and extract locomotion parameters in real-time. The combination of μPADs and the nematode tracking program provides a relatively low-cost, simple-to-fabricate imaging and screening assay (compared to standard agarose plates or polymeric microfluidic devices) for non-microfluidic, nematode laboratories.

This paper shows that a highly deformable capacitor made of a soft dielectric and two conformal electrodes can switch between two states discontinuously, by a first-order transition, as the total charge varies gradually. When the total charge is small, it spreads evenly over the area of the capacitor, and the capacitor deforms homogeneously. When the total charge is large, it localizes in a small region of the capacitor, and this region thins down preferentially. The capacitor will survive the localization without electrical breakdown if the area of the electrode is small. Such a bistable system may lead to useful devices., Engineering and Applied Sciences

The two-dimensional limit of layered materials has recently been realized through the use of van der Waals (vdW) heterostructures composed of weakly interacting layers. In this paper, we describe two different classes of vdW heterostructures: inorganic vdW heterostructures prepared by co-lamination and restacking; and organicinorganic hetero-epitaxy created by physical vapor deposition of organic molecule crystals on an inorganic vdW substrate. Both types of heterostructures exhibit atomically clean vdW interfaces. Employing such vdW heterostructures, we have demonstrated various novel devices, including graphene/hexagonal boron nitride (hBN) and MoS2 heterostructures for memory devices; graphene/MoS2/WSe2/graphene vertical p-n junctions for photovoltaic devices, and organic crystals on hBN with graphene electrodes for high-performance transistors, Physics

The highest quality pressures on samples in a diamond anvil cell (DAC) at high pressures are produced using quasi-hydrostatic pressurization media such as helium or hydrogen. In this paper we carry out a finite element analysis of pressure distributions in a DAC using helium and non-hydrostatic argon pressurization media. We find that samples and ruby chips are at substantially higher pressures than the pressurization media, although this is sharply reduced by using helium, which has a low yield strength for the shear modulus. The deviations in pressure of the different samples (and ruby) from the pressurization media differ and depend on their elastic constants. Our observations may account for the distribution of pressures in metallic markers found in a recent calibration of the ruby scale to high pressures., Physics

In this paper, we report our investigation of the translational energy relaxation of fast S((1)D) atoms in a Xe thermal bath. The interaction potential of Xe-S was constructed using ab initio methods. Total and differential cross sections were then calculated. The latter have been incorporated into the construction of the kernel of the Boltzmann equation describing the energy relaxation process. The solution of the Boltzmann equation was obtained and results were compared with those reported in experiments [G. Nan, and P. L. Houston, J. Chem. Phys. 97, 7865 (1992)]. Good agreement with the measured time-dependent relative velocity of fast S((1)D) atoms was obtained except at long relaxation times. The discrepancy may be due to the error accumulation caused by the use of hard sphere approximation and the Monte Carlo analysis of the experimental data. Our accurate description of the energy relaxation process led to an increase in the number of collisions required to achieve equilibrium by an order of magnitude compared to the number given by the hard-sphere approximation., Astronomy

Background: Type 2 diabetes mellitus (T2DM) is the most common type of diabetes, accounting for around 90% of all diabetes. Studies have found that dietary habits and biochemical metabolic changes are closely related to T2DM disease surveillance, but early surveillance tools are not specific and have lower accuracy. This paper aimed to provide a reliable artificial intelligence model with high accuracy for the clinical diagnosis of T2DM. Methods: A cross-sectional dataset comprising 8981 individuals from the First Affiliated Hospital of Guangxi Medical University was analyzed by a model fusion framework. The model includes four machine learning (ML) models, which used the stacking method. The ability to leverage the strengths of different algorithms to capture complex patterns in the data can effectively combine questionnaire data and blood test data to predict diabetes. Results: The experimental results show that the stacking model achieves significant prediction results in diabetes detection. Compared with the single machine learning algorithm, the stacking model has improved in the metrics of accuracy, recall, and F1-score. The test set accuracy is 0.90, and the precision, recall, F1-score, area under the curve, and average precision (AP) are 0.91, 0.90, 0.90, 0.90, and 0.85, respectively. Additionally, this study showed that HbA1c (P < 0.001,OR = 2.203), fasting blood glucose (FBG) (P < 0.001,OR = 1.586), Ph2BG (P < 0.001,OR = 1.190), age (P < 0.001,OR = 1.018), Han nationality (P < 0.001,OR = 1.484), and carbonate beverages (P = 0.001,OR = 1.347) were important predictors of T2DM. Conclusion: This study demonstrates that stacking models show great potential in diabetes detection, and by integrating multiple machine learning algorithms, stacking models can significantly improve the accuracy and stability of diabetes prediction and provide strong support for disease prevention, early diagnosis, and individualized treatment., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

Organic modification can generally endow inorganic materials with novel and promotional characteristics to fit into new functionalities. In this paper, new cement-based composite materials, with Portland cement as the substrate and polyacrylamide (PAM, alone) and PAM/chitosan as the functional components mixed with cement (bulk modified) or served as the surface coating (surface modified), were prepared and engineered as sampling substrates for biofilm and coral co-culture. In comparison to the bulk modified substrate and pure cement material, the surface modified substrate showed a balanced mechanical property, considering both bending and compressive strengths and distinctive surface features toward facilitating biofilm and coral growth, as characterized by spectroscopic, morphological, mechanical, and biofilm and coral co-culture experiments. We, thus, believe that the as-prepared surface modified substrate has the very potential to be applied as a substitute/alternative for the conventional cement material in the construction and engineering of artificial facilities with ecological protection functions., (2024 Published under an exclusive license by the AVS.)

The demand for ambulatory blood pressure monitoring (ABPM) is increasing due to the global rise in cardiovascular disease patients. However, conventional ABPM methods are discontinuous and can disrupt daily activities and sleep patterns. Photoplethysmography (PPG) is gaining attention from researchers due to its simplicity, portability, affordability, and ease of signal acquisition. This paper critically examines the advancements achieved in the technology of PPG-guided noninvasive blood pressure (BP) monitoring and explores future opportunities. We have performed a literature search using the Web of Science and PubMed search engines, from January 2018 to October 2023, for PPG signal quality assessment (SQA), cuffless BP estimation using single PPG, and associations between circadian rhythm and BP. Based on this foundation, we first examine the impact of PPG signal quality on blood pressure estimation results while focusing on methods for assessing PPG signal quality. Subsequently, the methods documented for estimating cuff-free BP from PPG signals are summarized. Furthermore, the study examines how individual differences affect the accuracy of BP estimation, incorporating the factors that influence arterial blood pressure (ABP) and elucidating the impact of circadian rhythm on blood pressure. Finally, there will be a summary of the study's findings and suggestions for future research directions., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

Novel hearable technology is securely and comfortably positioned within the ear canal minimizing inaccuracies caused by accessory movements during activities. Despite extensive research on hearable technologies within the outer ear, there is a lack of research in the field of vascular imaging and quantitative analysis in the outer ear in vivo , which is one of the crucial factors to select the appropriate sensor position. Therefore, in this paper, we introduced optical coherence tomography angiography (OCTA)-based qualitative and quantitative analyses to visualize the inner vasculature of the outer ear to acquire vascular maps for microvascular assessments in vivo . By generating maximum amplitude projection images from three-dimensional blood vascular volume, we identified variations of blood vessel signal caused by the different biological characteristics and curvature of the ear among individuals. The performance of micro-vascular mapping using the proposed method was validated through the comparison and analysis of individual vascular parameters using extracted 20 vascular-related variables. In addition, we extracted pulsatile blood flow signals, demonstrating its potential to provide photoplethysmographic signals and ear blood maps simultaneously. Therefore, our proposed OCTA-based method for ear vascular mapping successfully provides quantitative information about ear vasculature, which is potentially used for determining the position of system-on-chip sensors for health monitoring in hearable devices., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

Human platelet lysates (HPLs) from allogeneic platelet concentrates (PCs) are biomaterials, which are rich in various trophic factors, increasingly used in regenerative medicine and biotherapy. Understanding how preparation methods influence the HPL protein profile, biological function, and clinical outcomes is crucial. Our study sheds light on the proteomes and functionality of different HPLs, with the aim of advancing their scientifically grounded clinical applications. To achieve this, PCs suspended in plasma underwent three distinct processing methods, resulting in seven HPL types. We used three characterization techniques: label-free proteomics and tandem mass tag (TMT)-based quantitative proteomics, both before and after the immunodepletion of abundant plasma proteins. Bioinformatic tools assessed the proteome, and western blotting validated our quantitative proteomics data. Subsequent pre-clinical studies with fluorescent labeling and label-free proteomics were used as a proof of concept for brain diffusion. Our findings revealed 1441 proteins detected using the label-free method, 952 proteins from the TMT experiment before and after depletion, and 1114 proteins from the subsequent TMT experiment on depleted HPLs. Most detected proteins were cytoplasmic, playing key roles in catalysis, hemostasis, and immune responses. Notably, the processing methodologies significantly influenced HPL compositions, their canonical pathways, and, consequently, their functionality. Each HPL exhibited specific abundant proteins, providing valuable insight for tailored clinical applications. Immunoblotting results for selected proteins corroborated our quantitative proteomics data. The diffusion and differential effects to the hippocampus of a neuroprotective HPL administered intranasally to mice were demonstrated. This proteomics study advances our understanding of HPLs, suggesting ways to standardize and customize their production for better clinical efficacy in regenerative medicine and biotherapy. Proteomic analyses also offered objective evidence that HPPL, upon intranasal delivery, not only effectively diffuses to the hippocampus but also alters protein expression in mice, bolstering its potential as a treatment for memory impairments., Competing Interests: T.B. is one co-founder of Invenis Biotherapies and is listed as the inventor on patent applications owned by Taipei Medical University and University of Lille. The authors declare that they have no known competing financial interest or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Author(s).)

Lipid membranes and proteins, which are part of us throughout our lives, have been studied for decades. However, every year, new discoveries show how little we know about them. In a reader-friendly manner for people not involved in the field, this paper tries to serve as a bridge between physicists and biologists and new young researchers diving into the field to show its relevance, pointing out just some of the plethora of lines of research yet to be unraveled. It illustrates how new ways, from experimental to theoretical approaches, are needed in order to understand the structures and interactions that take place in a single lipid, protein, or multicomponent system, as we are still only scratching the surface., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).)

Planar supported lipid bilayers (PSLBs) are an ideal model for the study of lipid membrane structures and dynamics when using sum-frequency vibrational spectroscopy (SFVS). In this paper, we describe the construction of asymmetric PSLBs and the basic SFVS theory needed to understand and make measurements on these membranes. Several examples are presented, including the determination of phospholipid orientation and measuring phospholipid transmembrane translocation (flip-flop)., (2024 Published under an exclusive license by the AVS.)

This paper introduces a physical neuron model that incorporates magnetoelectric nanoparticles (MENPs) as an essential electrical circuit component to wirelessly control local neural activity. Availability of such a model is important as MENPs, due to their magnetoelectric effect, can wirelessly and noninvasively modulate neural activity, which, in turn, has implications for both finding cures for neurological diseases and creating a wireless noninvasive high-resolution brain-machine interface. When placed on a neuronal membrane, MENPs act as magnetic-field-controlled finite-size electric dipoles that generate local electric fields across the membrane in response to magnetic fields, thus allowing to controllably activate local ion channels and locally initiate an action potential. Herein, the neuronal electrical characteristic description is based on ion channel activation and inhibition mechanisms. A MENP-based memristive Hodgkin-Huxley circuit model is extracted by combining the Hodgkin-Huxley model and an equivalent circuit model for a single MENP. In this model, each MENP becomes an integral part of the neuron, thus enabling wireless local control of the neuron's electric circuit itself. Furthermore, the model is expanded to include multiple MENPs to describe collective effects in neural systems., (2024 Published under an exclusive license by the AVS.)

Cancer, with high morbidity and high mortality, is one of the major burdens threatening human health globally. Intervention procedures via percutaneous puncture have been widely used by physicians due to its minimally invasive surgical approach. However, traditional manual puncture intervention depends on personal experience and faces challenges in terms of precisely puncture, learning-curve, safety and efficacy. The development of puncture interventional surgery robotic (PISR) systems could alleviate the aforementioned problems to a certain extent. This paper attempts to review the current status and prospective of PISR systems for thoracic and abdominal application. In this review, the key technologies related to the robotics, including spatial registration, positioning navigation, puncture guidance feedback, respiratory motion compensation, and motion control, are discussed in detail., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

Meta-biomaterials, engineered materials with distinctive combinations of mechanical, physical, and biological properties stemming from their micro-architecture, have emerged as a promising domain within biomedical engineering. Correspondingly, meta-implants, which serve as the device counterparts of meta-biomaterials, offer exceptional functionalities, holding great potential for addressing complex skeletal diseases. This paper presents a comprehensive overview of the various types of meta-implants, including hybrid, shape-morphing, metallic clay, and deployable meta-implants, highlighting their unprecedented properties and recent achievement in the field. This paper also delves into the potential future developments of meta-implants, addressing the exploration of multi-functionalities in meta-biomaterials and their applications in diverse biomedical fields., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

In transitioning toward a sustainable economy, mycelial materials are recognized for their adaptability, biocompatibility, and eco-friendliness. This paper updates the exploration of mycelial materials, defining their scope and emphasizing the need for precise terminology. It discusses the importance of mycelial type and characteristics, reviews existing and future research directions, and highlights the need for improved understanding, clarity, and standardization in this emerging field, aiming to foster and guide future research and development in sustainable material science., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)

Unlike conventional glasses, corneal contact lenses (CLs) can directly contact the surface of the tear film through the application of biopolymer materials, to achieve therapeutic and cosmetic purposes. Since the advent of polymethylmethacrylate, a material that has gained widespread use and attention, statistically, there are now more than 150 × 106 people around the world who wear corneal contact lenses. However, the associated complications caused by the interaction of contact lenses with the ocular surface, tear film, endogenous and environmental microorganisms, and components of the solution affect nearly one-third of the wearer population. The application of corneal contact lenses in correcting vision and myopia control has been widely recognized. With the development of related materials, corneal contact lenses are applied to the treatment of ocular surface diseases, including corneal bandage lenses, drug-loaded corneal contact lenses, biosensors, and other new products, while minimizing the side effects associated with CL wear. This paper summarized the development history and material properties of CLs, focused on the current main clinical applications and mechanisms, as well as clarified the possible complications in wearing therapeutic contact lenses and the direction for improvement in the future., (2023 Published under an exclusive license by the AVS.)

Asthma is often characterized by tissue-level mechanical phenotypes that include remodeling of the airway and an increase in airway tightening, driven by the underlying smooth muscle. Existing therapies only provide symptom relief and do not improve the baseline narrowing of the airway or halt progression of the disease. To investigate such targeted therapeutics, there is a need for models that can recapitulate the 3D environment present in this tissue, provide phenotypic readouts of contractility, and be easily integrated into existing assay plate designs and laboratory automation used in drug discovery campaigns. To address this, we have developed DEFLCT, a high-throughput plate insert that can be paired with standard labware to easily generate high quantities of microscale tissues in vitro for screening applications. Using this platform, we exposed primary human airway smooth muscle cell-derived microtissues to a panel of six inflammatory cytokines present in the asthmatic niche, identifying TGF-β1 and IL-13 as inducers of a hypercontractile phenotype. RNAseq analysis further demonstrated enrichment of contractile and remodeling-relevant pathways in TGF-β1 and IL-13 treated tissues as well as pathways generally associated with asthma. Screening of 78 kinase inhibitors on TGF-β1 treated tissues suggests that inhibition of protein kinase C and mTOR/Akt signaling can prevent this hypercontractile phenotype from emerging, while direct inhibition of myosin light chain kinase does not. Taken together, these data establish a disease-relevant 3D tissue model for the asthmatic airway, which combines niche specific inflammatory cues and complex mechanical readouts that can be utilized in drug discovery efforts., Competing Interests: Yes, all authors are current or prior employees (were employees at the time of their contributions to the paper) of Novartis., (© 2023 Author(s).)

In this paper, we stimulated M1-like macrophages (obtained from U937 cells) with low-intensity pulsed ultrasound (LIPUS) to lower pro-inflammatory cytokine production. A systematic screening of different frequencies, intensities, duty cycles, and exposure times was performed. The optimal stimulation conditions leading to a marked decrease in the release of inflammatory cytokines were determined to be 38 kHz, 250 mW/cm 2 , 20%, and 90 min, respectively. Using these parameters, we verified that up to 72 h LIPUS did not affect cell viability, resulting in an increase in metabolic activity and in a reduction of reactive oxygen species (ROS) production. Moreover, we found that two mechanosensitive ion channels (PIEZO1 and TRPV1) were involved in the LIPUS-mediated cytokine release modulation. We also assessed the role of the nuclear factor κB (NF-κB) signaling pathway and observed an enhancement of actin polymerization. Finally, transcriptomic data suggested that the bioeffects of LIPUS treatment occur through the modulation of p38 MAPK signaling pathway., Competing Interests: The authors have no conflicts to disclose., (© 2023 Author(s).)

When polymer chains are grafted to solid surfaces at sufficiently high density, they form brushes that can modify the surface properties. In particular, polymer brushes are increasingly being used to reduce friction in water-lubricated systems close to the very low levels found in natural systems, such as synovial joints. New types of polymer brush are continually being developed to improve with lower friction and adhesion, as well as higher load-bearing capacities. To complement experimental studies, molecular simulations are increasingly being used to help to understand how polymer brushes reduce friction. In this paper, we review how molecular simulations of polymer brush friction have progressed from very simple coarse-grained models toward more detailed models that can capture the effects of brush topology and chemistry as well as electrostatic interactions for polyelectrolyte brushes. We pay particular attention to studies that have attempted to match experimental friction data of polymer brush bilayers to results obtained using molecular simulations. We also critically look at the remaining challenges and key limitations to overcome and propose future modifications that could potentially improve agreement with experimental studies, thus enabling molecular simulations to be used predictively to modify the brush structure for optimal friction reduction.

The scientific community has shown increasing interest in laser scribing for the direct fabrication of conductive graphene-based tracks on different substrates. This can enable novel routes for the noninvasive analysis of biofluids (such as sweat or other noninvasive matrices), whose results can provide the rapid evaluation of a person's health status. Here, we present a wearable sensing platform based on laser induced graphene (LIG) porous electrodes scribed on a flexible polyimide sheet, which samples sweat through a paper sampler. The device is fully laser manufactured and features a two layer design with LIG-based vertical interconnect accesses. A detailed characterization of the LIG electrodes including pore size, surface groups, surface area in comparison to electroactive surface area, and the reduction behavior of different LIG types was performed. The bare LIG electrodes can detect the electrochemical oxidation of both uric acid and tyrosine. Further modification of the surface of the LIG working electrode with an indoaniline derivative [4-((4-aminophenyl)imino)-2,6-dimethoxycyclohexa-2,5-dien-1-one] enables the voltammetric measurement of pH with an almost ideal sensitivity and without interference from other analytes. Finally, electrochemical impedance spectroscopy was used to measure the concentrations of ions through the analysis of the sweat impedance. The device was successfully tested in a real case scenario, worn on the skin during a sports session. In vitro tests proved the non-cytotoxic effect of the device on the A549 cell line., (© 2022 Author(s).)

This paper summarizes the early research results on studying proteins and peptides at interfaces using sum frequency generation (SFG) vibrational spectroscopy. SFG studies in the C-H stretching frequency region to examine the protein side-chain behavior and in the amide I frequency region to investigate the orientation and conformation of interfacial peptides/proteins are presented. The early chiral SFG research and SFG isotope labeling studies on interfacial peptides/proteins are also discussed. These early SFG studies demonstrate the feasibility of using SFG to elucidate interfacial molecular structures of peptides and proteins in situ, which built a foundation for later SFG investigations on peptides and proteins at interfaces.

Atomic spectroscopy and atomic physics papers represent a significant part of publications in Journal of Physical and Chemical Reference Data (JPCRD). Critical compilations of spectroscopic data, accurate calculations of collisional parameters, and bibliography on spectral line profiles and shifts provided much needed information for plasma physics, astrophysics, lithography, fusion research, and other fields of science. We present a brief overview of the atomic physics research published in JPCRD over its first 50 years., Competing Interests: 6.1. Conflict of Interest The author has no conflicts to disclose.

Skin is one of the indispensable organs for life. The epidermis at the outermost surface provides a permeability barrier to infectious agents, chemicals, and excessive loss of water, while the dermis and subcutaneous tissue mechanically support the structure of the skin and appendages, including hairs and secretory glands. The integrity of the integumentary system is a key for general health, and many techniques have been developed to measure and control this protective function. In contrast, the effective skin barrier is the major obstacle for transdermal delivery and detection. Changes in the electrical properties of skin, such as impedance and ionic activity, is a practical indicator that reflects the structures and functions of the skin. For example, the impedance that reflects the hydration of the skin is measured for quantitative assessment in skincare, and the current generated across a wound is used for the evaluation and control of wound healing. Furthermore, the electrically charged structure of the skin enables transdermal drug delivery and chemical extraction. This paper provides an overview of the electrical aspects of the skin and summarizes current advances in the development of devices based on these features., (© 2021 Author(s).)

Hepatocytes are parenchymal cells of the liver responsible for drug detoxification, urea and bile production, serum protein synthesis, and glucose homeostasis. Hepatocytes are widely used for drug toxicity studies in bioartificial liver devices and for cell-based liver therapies. Because hepatocytes are highly differentiated cells residing in a complex microenvironment in vivo , they tend to lose hepatic phenotype and function in vitro . This paper first reviews traditional culture approaches used to rescue hepatic function in vitro and then discusses the benefits of emerging microfluidic-based culture approaches. We conclude by reviewing integration of hepatocyte cultures with bioanalytical or sensing approaches., (© 2021 Author(s).)

The complexity of the human brain creates significant, almost insurmountable challenges for neurological drug development. Advanced in vitro platforms are increasingly enabling researchers to overcome these challenges, by mimicking key features of the brain's composition and functionality. Many of these platforms are called "Brains-on-a-Chip"-a term that was originally used to refer to microfluidics-based systems containing miniature engineered tissues, but that has since expanded to describe a vast range of in vitro central nervous system (CNS) modeling approaches. This Perspective seeks to refine the definition of a Brain-on-a-Chip for the next generation of in vitro platforms, identifying criteria that determine which systems should qualify. These criteria reflect the extent to which a given platform overcomes the challenges unique to in vitro CNS modeling (e.g., recapitulation of the brain's microenvironment; inclusion of critical subunits, such as the blood-brain barrier) and thereby provides meaningful added value over conventional cell culture systems. The paper further outlines practical considerations for the development and implementation of Brain-on-a-Chip platforms and concludes with a vision for where these technologies may be heading., (© 2021 Author(s).)

A prominent feature of coronaviruses is the presence of a large glycoprotein spike protruding from a lipidic membrane. This glycoprotein spike determines the interaction of coronaviruses with the environment and the host. In this paper, we perform all atomic molecular dynamics simulations of the interaction between the SARS-CoV-2 trimeric glycoprotein spike and surfaces of materials. We considered a material with high hydrogen bonding capacity (cellulose) and a material capable of strong hydrophobic interactions (graphite). Initially, the spike adsorbs to both surfaces through essentially the same residues belonging to the receptor binding subunit of its three monomers. Adsorption onto cellulose stabilizes in this configuration, with the help of a large number of hydrogen bonds developed between cellulose and the three receptor-binding domains of the glycoprotein spike. In the case of adsorption onto graphite, the initial adsorption configuration is not stable and the surface induces a substantial deformation of the glycoprotein spike with a large number of adsorbed residues not pertaining to the binding subunits of the spike monomers.

The cardiovascular system demonstrates left-right (LR) asymmetry: most notably, the LR asymmetric looping of the bilaterally symmetric linear heart tube. Similarly, the orientation of the aortic arch is asymmetric as well. Perturbations to the asymmetry have been associated with several congenital heart malformations and vascular disorders. The source of the asymmetry, however, is not clear. Cell chirality, a recently discovered and intrinsic LR asymmetric cellular morphological property, has been implicated in the heart looping and vascular barrier function. In this paper, we summarize recent advances in the field of cell chirality and describe various approaches developed for studying cell chirality at multi- and single-cell levels. We also examine research progress in asymmetric cardiovascular development and associated malformations. Finally, we review evidence connecting cell chirality to cardiac looping and vascular permeability and provide thoughts on future research directions for cell chirality in the context of cardiovascular development and disease., (© 2020 Author(s).)

The controlled modification of surface properties represents a pervasive requirement to be fulfilled when developing new technologies. In this paper, we propose an easy-to-implement protocol for the functionalization of glass with self-assembled monolayers (SAMs). The adaptivity of the synthesis route was demonstrated by the controlled anchoring of thiol, amino, glycidyloxy, and methacrylate groups onto the glass surface. The optimization of the synthetic pathway was mirrored by extremely smooth SAMs (approximately 150 pm roughness), layer thickness comparable to the theoretical molecule length, absence of silane islands along the surface, quasi-unitary degree of packing, and tailored wettability and charge. The functionalization kinetics of two model silanes, 3-mercapto- and 3-amino-propyltrimethoxysilane, was determined by cross-comparing x-ray photoelectron spectroscopy and time of flight secondary ion mass spectrometry data. Our SAMs with tailored physicochemical attributes will be implemented as supports for the crystallization of pharmaceuticals and biomolecules in upcoming studies. Here, the application to a small molecule drug model, namely aspirin, was discussed as a proof of concept.

Many individuals perform cell viability assays as a measure of biocompatibility whether the focus of their research is on novel drug discovery, development of novel biomedical devices, or the study of biointerfacial phenomena. In this tutorial paper, the most commonly used methods available to users to perform biocompatibility testing are discussed. This includes a brief introduction into the benefits and drawbacks of the techniques, including which are best used as screening assays, which are better suited to experienced users, the relative cost of the assays per unit, and what detection techniques are most appropriate for use in conjunction with the assays. In addition to helping users ensure the rigor and reproducibility of their research design, this tutorial is meant to assist reviewers of interdisciplinary journals (such as Biointerphases itself), whose expertise is in other areas of this research but do not have the experience with cell-based assays themselves.

The most common bulk acoustic wave device used in biosensing applications is the quartz crystal microbalance (QCM), in which a resonant pure shear acoustic wave is excited via electrodes on both major faces of a thin AT-cut quartz plate. For biosensing, the QCM is used to detect the capture of a target by a target-capture film. The sensitivity of the QCM is typically based solely on the detection of mechanical property changes, as electrical property change detection is limited by the electrode on its sensing surface. A modification of the QCM called the lateral field excited (LFE) QCM (LFE-QCM) has been developed with a bare sensing surface as both electrodes are now on a single face of the quartz plate. Compared to the QCM, the LFE-QCM exhibits significantly higher sensitivity to both electrical and mechanical property changes. This paper presents theoretical and experimental aspects of LFE-QCMs. In particular, the presence and strength of the usual and newfound LFE-QCM modes depend on the electrical properties of the film and/or sensing environment. This work also presents examples of experimental setups for measuring the response of an LFE-QCM, followed by results of LFE-QCMs used to detect liquid electrical and mechanical properties, chemical targets, and biological targets. Finally, details are given about the attachment of various target-capture films to the LFE-QCM surface to capture biomarkers associated with diseases such as cancer.

This paper presents the use of a commercial quartz crystal microbalance (QCM) to investigate live-cell activity in water-based toxic solutions. The QCM used in this research has a resonant frequency of 10 MHz and consists of an AT-cut quartz crystal with gold electrodes on both sides. This QCM was transformed into a functional biosensor by integrating with polydimethylsiloxane culturing chambers. Rainbow trout gill epithelial cells were cultured on the resonators as a sensorial layer. The fluctuation of the resonant frequency, due to the change of cell morphology and adhesion, is an indicator of water toxicity. The shift in the resonant frequency provides information about the viability of the cells after exposure to toxicants. The toxicity result shows distinct responses after exposing cells to 0.526 μM of pentachlorophenol (PCP) solution, which is the Military Exposure Guidelines concentration. This research demonstrated that the QCM is sensitive to a low concentration of PCP and no further modification of the QCM surface was required.

This Perspective paper advances a hypothesis of mechanosensation by endothelial cells in which the cell is a dynamic crowded system, driven by continuous enzyme activity, that can be shifted from one non-equilibrium state to another by external force. The nature of the shift will depend on the direction, rate of change, and magnitude of the force. Whether force induces a pathophysiological or physiological change in cell biology will be determined by whether the dynamics of a cellular system can accommodate the dynamics and magnitude of the force application. The complex interplay of non-static cytoskeletal structures governs internal cellular rheology, dynamic spatial reorganization, and chemical kinetics of proteins such as integrins, and a flaccid membrane that is dynamically supported; each may constitute the necessary dynamic properties able to sense external fluid shear stress and reorganize in two and three dimensions. The resulting reorganization of enzyme systems in the cell membrane and cytoplasm may drive the cell to a new physiological state. This review focuses on endothelial cell mechanotransduction of shear stress, but may lead to new avenues of investigation of mechanobiology in general requiring new tools for interrogation of mechanobiological systems, tools that will enable the synthesis of large amounts of spatial and temporal data at the molecular, cellular, and system levels., (© Author(s).)

Ti-6Al-4V alloy, as a widely used orthopedic and dental implant, has excellent biocompatibility and machinability. However, its poor corrosion resistance and antibacterial property may lead to tissue inflammation and postoperative infection, which hinders its further development. In this paper, to solve the above problems, copper (Cu) and zinc (Zn) ions were coimplanted into a titanium nitride (TiN) coated Ti-6Al-4V alloy via a plasma immersion ion implantation system (PIII). Then, the structure and composition of Cu/Zn coimplanted TiN (Cu/Zn-TiN-PIII) were characterized by scanning electron microscopy and x-ray photoelectron spectroscopy. Also, the results of the corrosion test, the water contact angles test, and the protein electrophoresis experiment showed that the corrosion resistance, hydrophilicity, and the protein adsorption capacity of Cu/Zn-TiN-PIII were improved simultaneously. In addition, compared with TiN-PIII, Cu/Zn-TiN-PIII promoted both cytocompatibility and the antibacterial property according to L929 cells and Escherichia coli assays in vitro. Therefore, Cu/Zn-TiN-PIII may be a good candidate for orthopedic implants.

Networks of amyloid-like nanofibrils assembled from short peptide sequences have the ability to form scaffolds that can encapsulate clinically relevant stem cells encouraging their attachment, growth, and differentiation into various lineages which can be used in tissue engineering applications to treat a range of diseases and traumas. In this review, the author highlights a selection of important proof-of-principle papers that show how this class of self-assembled networks is highly suited to biomaterial scaffold development. The author highlights recent studies which have shown that these scaffolds can be used to promote cell and tissue regeneration both in vitro and in vivo. The author also presents some fundamental knowledge gaps which are preventing the widespread translation of such scaffolds. Finally, the author outlines a selection of studies that elucidate molecular assembly mechanisms and biophysical properties of amyloid-like peptide nanofibrils and suggests how studies like these might lead to the ability to generate nanofibril scaffolds with bespoke properties for tissue engineering.

Monitoring cell metabolism in vitro is considered a relevant methodology in several scientific fields ranging from fundamental biology research to neuro-toxicology. In the last 20 years, several in vitro neuro-pharmacological and neuro-toxicological approaches have been developed, with the intent of addressing the increasing demand for real-time, non-invasive in vitro systems capable of continuously and reliably monitoring cellular activity. In this paper, an Organic Charge Modulated Field Effect Transistor-based device is proposed as a promising tool for neuro-pharmacological applications, thanks to its ultra-high pH sensitivity and a simple fabrication technology. The preliminary characterization of this versatile organic device with primary neuronal cultures shows how these remarkable properties can be exploited for the realization of ultra-sensitive metabolic probes, which are both reference-less and low cost. These features, together with the already assessed capability of this sensor to also monitor the electrical activity of electrogenic cells, could provide important advances in the fabrication of multi-sensing lab-on-chip devices, thus opening up interesting perspectives in the neuro-pharmacological field.

This paper provides an empirical formula to calculate the extinction efficiencies of gold nanoparticles over the size range 1-1000 nm in fluids with refractive indexes which extend from n  = 1 to n  = 1.62. The formula contains a shape factor to account for nonspherical particles and aggregates. The empirical curves are fitted to values calculated from accurate Mie and T-Matrix theory and confirm previous descriptions which are restricted to nearly spherical particles in water of diameter between 5 and 100 nm. This paper demonstrates that these previous descriptions will be in error for fluids other than water and for nonspherical particles greater than 100 nm in size. An empirical description is provided which matches calculated values to within a few percent across most of the range. The description also matches experimental data to within the standard relative error, currently 5% at best, using other methods which directly measure the particle concentration. These extinction efficiencies can be used to validate the concentration of gold nanoparticles in a wide range of situations to support the drive for reproducibility in nanoparticle research.

Electrocardiography is a valuable tool to aid in medical understanding and treatment of heart-related ailments, specifically atrial fibrillation (AF) and other irregular cardiac behavior. Although signs of AF will manifest in conventional electrocardiogram (ECG) recordings, interpretation and localization of AF sources require significant clinical expertise. In this vein, electrocardiographic imaging has emerged as an important medical imaging modality that provides reconstructions of the heart's electrical activity from non-invasive multi-lead body-surface ECG and anatomical x-ray computed tomography images. In this paper, we present a nonlinear inversion model for computing this mapping to improve upon the reconstruction performance of current methods. While contemporary techniques typically determine an inverse solution by discretizing and inverting an underdetermined linear system of partial differential equations governing the relationship between voltage potentials of the heart and torso, the presented technique re-casts this problem as a task in function approximation and provides a direct parameterization of the inverse operator using a polynomial neural network. That is, the outlined nonlinear inversion technique is a generalization of contemporary reconstruction techniques which allows geometrical and material parameterizations of the forward-model to be optimized using real experimental data collected from patients suffering from AF, as to better represent the inverse operator with respect to reconstruction metrics applicable to electrophysiology. The accuracy of our model is evaluated against a dataset of real-patient recordings to demonstrate its validity, and mathematical analysis is provided to support the polynomial expansion used in our inversion model.

Recent technological breakthroughs in our ability to derive and differentiate induced pluripotent stem cells, organoid biology, organ-on-chip assays, and 3-D bioprinting have all contributed to a heightened interest in the design, assembly, and manufacture of living systems with a broad range of potential uses. This white paper summarizes the state of the emerging field of "multi-cellular engineered living systems," which are composed of interacting cell populations. Recent accomplishments are described, focusing on current and potential applications, as well as barriers to future advances, and the outlook for longer term benefits and potential ethical issues that need to be considered.

This paper critically reviews the current evidence of research in biomedical applications of selenium nanoparticles (SeNPs) and their effects at cellular and tissue levels. In recent years, interest in SeNPs as a natural trace element nanomaterial for nanomedicine has resulted in a number of studies evaluating their bioactivities, such as anticancer, antimicrobial, and antioxidant properties. Significant data have been generated to demonstrate the effectiveness of SeNPs alone or in combination with other reagents. Their activities are demonstrated through in vitro and in vivo experimentation; yet, the levels of efficacy need to be improved, particularly when compared with those of pharmaceutical drugs (such as antibiotics and cytotoxic chemotherapeutic drugs). However, promising evidence suggests decreased toxicity when using SeNPs, and more importantly their ability to perform as an interfacing biomaterial with cells and tissues. SeNPs have demonstrated unique antibacterial properties: they inhibit bacterial adhesion, growth, and/or quorum sensing and as a result prevent biofilm formation on medical devices, to name a few. Therefore, as with other nanomaterials, SeNPs warrant further study as part of the biomaterial-based therapeutic toolkit as an alternative to traditional pharmaceutical agents. This paper will provide a succinct review of recent studies on SeNPs to critically assess the findings in the light of effectiveness, particularly highlighting the roles of the cellular interface. Finally, an outlook of the potential of SeNPs will be presented to highlight the need for more intensive studies of material stability, mechanistic understanding at subcellular levels, and investigations into their combinational and/or synergistic effects with other bioactive reagents including pharmaceutical drugs.

It is well known that at the interface between neuronal tissue and recording electrode low electrical impedance is required. However, if simultaneous optical detection or stimulation is an issue, good optical transmittance of the electrode material is desirable as well. State-of-the-art titanium nitride electrodes provide superior low impedance compared to gold or iridium, but are nontransparent. Transparent electrode materials like the transparent conducting oxide, indium tin oxide (ITO), or graphene offer high light transmittance (>80%) but reveal relatively high impedance. In this paper, the authors propose the conducting polymer poly(3,4-ethylenedioxythiophene) with the counter ion NO 3 - as the electrode material for low impedance and good optical transmittance properties. The polymer is electrochemically deposited onto ITO improving the relatively high impedance of ITO. This multilayer electrode allows not only for electrophysiological recordings of cardiomyocytes but also for monitoring of cell contraction under the microscope. Electrochemical impedance spectroscopy and action potential recordings reveal that the new transparent electrodes are a good compromise in terms of low impedance and transparency if deposition parameters are optimized.

Collective motions of groups of cells are observed in many biological settings such as embryo development, tissue formation, and cancer metastasis. To effectively model collective cell movement, it is important to incorporate cell specific features such as cell size, cell shape, and cell mechanics, as well as active behavior of cells such as protrusion and force generation, contractile forces, and active biochemical signaling mechanisms that regulate cell behavior. In this paper, we develop a comprehensive model of collective cell migration in confluent epithelia based on the vertex modeling approach. We develop a method to compute cell-cell viscous friction based on the vertex model and incorporate RhoGTPase regulation of cortical myosin contraction. Global features of collective cell migration are examined by computing the spatial velocity correlation function. As active cell force parameters are varied, we found rich dynamical behavior. Furthermore, we find that cells exhibit nonlinear phenomena such as contractile waves and vortex formation. Together our work highlights the importance of active behavior of cells in generating collective cell movement. The vertex modeling approach is an efficient and versatile approach to rigorously examine cell motion in the epithelium.

Assessing the efficiency of the next generation of protective marine coatings is highly relevant for their optimization. In this paper, a parallelized microfluidic testing device is presented to quantify the accumulation of a model organism (Navicula perminuta) under constant laminar flow. Using automated microscopy in conjunction with image analysis, the adhesion densities on the tested surfaces could be determined after exposure to a flow of suspended algae for 90 min. The optimized protocol for the assay is presented, and the reproducibility of the densities of attached diatoms was verified on four identical surfaces (self-assembled dodecanethiol monolayers). A set of well-characterized self-assembled monolayers with different chemical terminations was used to validate the performance of the assay and its capability to discriminate diatom accumulation on different surface chemistries under dynamic conditions. The observed trends are in good agreement with previously published results obtained in single channel accumulation and detachment assays. To demonstrate the practical relevance of the dynamic experiment, diatom attachment on four technically relevant silicone coatings with different fouling-release properties could clearly be distinguished.

Most soft biological tissues exhibit a remarkable ability to adapt to sustained changes in mechanical loads. These macroscale adaptations, resulting from mechanobiological cellular responses, are important determinants of physiological behaviors and thus clinical outcomes. Given the complexity of such adaptations, computational models can significantly increase our understanding of how contributions of different cell types or matrix constituents, and their rates of turnover and evolving properties, ultimately change the geometry and biomechanical behavior at the tissue level. In this paper, we examine relative roles of the rates of tissue responses and external loading and present a new rate-independent approach for modeling the evolution of soft tissue growth and remodeling. For illustrative purposes, we also present numerical results for arterial adaptations. In particular, we show that, for problems defined by particular characteristic times, this approximate theory captures well the predictions of a fully general constrained mixture theory at a fraction of the computational cost.

One of the key challenges in engineering tissues for cell-based therapies is developing biocompatible scaffold materials to direct cell behavior. In this paper, the cytocompatibilities of a flexible three-dimensional graphene scaffold (3D-G) and the same scaffold implanted with nitrogen ions (N + /3D-G) are compared using an in vitro assay based on 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. The N + /3D-G samples were prepared from low-temperature hydrothermally synthesized flexible 3D-G by ion implantation and were found to display improved adhesion and proliferation of rat osteoblast and mouse fibroblast cells. In particular, the N + /3D-G sample with a nitrogen content of ∼10% showed the highest levels of cell viability and proliferation. The flexible N + /3D-G has potential applications as a biocompatible scaffold material that provides improved surface area and hydrophilic groups for cell growth and proliferation.

Brain imaging using time-of-flight secondary ion mass spectrometry (ToF-SIMS) has been reported to produce the distorted biomolecular distributions due to the cholesterol-induced matrix effect when cholesterol migrates to the surface, particularly in white matter, which contains a high level of cholesterol. Frozen-hydrated analysis has been used to inhibit the movement of cholesterol in the brain. In this paper, the authors propose new sample preparation and drying methods that can be used to obtain accurate biomolecular images at room temperature, instead of frozen-hydrated analysis using liquid-nitrogen, which must be continuously supplied to maintain the sample at -160 °C during the experiment. The rat brain prepared by the tape-supporting method on a precooled (-20 °C) stainless steel plate was freeze-dried in a load-lock chamber of ToF-SIMS for about an hour and moved directly to the main chamber. Using this preparation method, the authors found that cholesterol did not migrate to the surface in the corpus callosum (white matter) of the rat brain and sulfatide-related signals obtained from the cerebellum were not reduced in white matter. Our tape-supporting and freeze-drying sampling method for brain tissues could be a useful tool to study important metabolites of neurodegenerative diseases.

In this paper, reference values and reference correlations for the thermal conductivity and viscosity of pure fluids are reviewed. Reference values and correlations for the thermal conductivity and the viscosity of pure fluids provide thoroughly evaluated data or functional forms and serve to help calibrate instruments, validate or extend models, and underpin some commercial transactions or designs, among other purposes. The criteria employed for the selection of thermal conductivity and viscosity reference values are also discussed; such values, which have the lowest uncertainties currently achievable, are typically adopted and promulgated by international bodies. Similar criteria are employed in the selection of reference correlations, which cover a wide range of conditions, and are often characterized by low uncertainties in their ranges of definition.

This paper presents a new wide-ranging correlation for the viscosity of ammonia based on critically evaluated experimental data. The correlation is designed to be used with a recently developed equation of state, and it is valid from the triple point to 725 K, at pressures up to 50 MPa. The estimated uncertainty varies depending on the temperature and pressure, from 0.6% to 5%. The correlation behaves in a physically reasonable manner when extrapolated to 100 MPa, however care should be taken when using the correlations outside of the validated range.