Moderating Effect of Burnout on the Relationship between Self-Efficacy and Job Performance among Psychiatric Nurses for COVID-19 in National Hospitals.

Background and Objective: The unprecedented spread of infectious diseases, such as the COVID-19 pandemic, in psychiatric units has affected the self-efficacy, burnout, and job performances of psychiatric nurses. We conducted a survey to investigate the moderating effect of burnout on the relationship between the self-efficacy and job performances of psychiatric nurses. Materials and Methods: Validated and structured questionnaires were used to collect data from 186 nurses in psychiatric units for COVID-19. The data were analyzed using descriptive statistics, Pearson's correlation coefficient, and a series of multiple linear regression analyses based on Baron and Kenny's method using the SPSS 26.0 program. Results: Job performance was positively correlated with self-efficacy (r = 0.75, p < 0.001) but had no significant correlation with burnout (r = -0.11, p = 0.150). Self-efficacy was negatively correlated with burnout (r = -0.22, p = 0.002). Burnout among psychiatric nurses had significant moderating effects on self-efficacy and job performance (ß = -0.11, p = 0.024). Conclusions: These findings indicate a need to prevent burnout and to enhance self-efficacy in psychiatric nurses to increase their job performances and serve as a basis for establishing strategies to deploy medical staff in the future.

Label-Free and Regenerative Electrochemical Microfluidic Biosensors for Continual Monitoring of Cell Secretomes.

Development of an efficient sensing platform capable of continual monitoring of biomarkers is needed to assess the functionality of the in vitro organoids and to evaluate their biological responses toward pharmaceutical compounds or chemical species over extended periods of time. Here, a novel label-free microfluidic electrochemical (EC) biosensor with a unique built-in on-chip regeneration capability for continual measurement of cell-secreted soluble biomarkers from an organoid culture in a fully automated manner without attenuating the sensor sensitivity is reported. The microfluidic EC biosensors are integrated with a human liver-on-a-chip platform for continual monitoring of the metabolic activity of the organoids by measuring the levels of secreted biomarkers for up to 7 d, where the metabolic activity of the organoids is altered by a systemically applied drug. The variations in the biomarker levels are successfully measured by the microfluidic regenerative EC biosensors and agree well with cellular viability and enzyme-linked immunosorbent assay analyses, validating the accuracy of the unique sensing platform. It is believed that this versatile and robust microfluidic EC biosensor that is capable of automated and continual detection of soluble biomarkers will find widespread use for long-term monitoring of human organoids during drug toxicity studies or efficacy assessments of in vitro platforms.

Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors.

Organ-on-a-chip systems are miniaturized microfluidic 3D human tissue and organ models designed to recapitulate the important biological and physiological parameters of their in vivo counterparts. They have recently emerged as a viable platform for personalized medicine and drug screening. These in vitro models, featuring biomimetic compositions, architectures, and functions, are expected to replace the conventional planar, static cell cultures and bridge the gap between the currently used preclinical animal models and the human body. Multiple organoid models may be further connected together through the microfluidics in a similar manner in which they are arranged in vivo, providing the capability to analyze multiorgan interactions. Although a wide variety of human organ-on-a-chip models have been created, there are limited efforts on the integration of multisensor systems. However, in situ continual measuring is critical in precise assessment of the microenvironment parameters and the dynamic responses of the organs to pharmaceutical compounds over extended periods of time. In addition, automated and noninvasive capability is strongly desired for long-term monitoring. Here, we report a fully integrated modular physical, biochemical, and optical sensing platform through a fluidics-routing breadboard, which operates organ-on-a-chip units in a continual, dynamic, and automated manner. We believe that this platform technology has paved a potential avenue to promote the performance of current organ-on-a-chip models in drug screening by integrating a multitude of real-time sensors to achieve automated in situ monitoring of biophysical and biochemical parameters.

Unbiased Analysis of the Impact of Micropatterned Biomaterials on Macrophage Behavior Provides Insights beyond Predefined Polarization States.

Macrophages are master regulators of immune responses toward implanted biomaterials. The activation state adopted by macrophages in response to biomaterials determines their own phenotype and function as well as those of other resident and infiltrating immune and nonimmune cells in the area. A wide spectrum of macrophage activation states exists, with M1 (pro-inflammatory) and M2 (anti-inflammatory) representing either ends of the spectrum. In biomaterials research, cell-instructive surfaces that favor or induce M2 macrophages have been considered as beneficial due to the anti-inflammatory and pro-regenerative properties of these cells. In this study, we used a gelatin methacryloyl (GelMA) hydrogel platform to determine whether micropatterned surfaces can modulate the phenotype and function of human macrophages. The effect of microgrooves/ridges and micropillars on macrophage phenotype, function, and gene expression profile were assessed using conventional methods (morphology, cytokine profile, surface marker expression, phagocytosis) and gene microarrays. Our results demonstrated that micropatterns did induce distinct gene expression profiles in human macrophages cultured on microgrooves/ridges and micropillars. Significant changes were observed in genes related to primary metabolic processes such as transcription, translation, protein trafficking, DNA repair, and cell survival. However, interestingly conventional phenotyping methods, relying on surface marker expression and cytokine profile, were not able to distinguish between the different conditions, and indicated no clear shift in cell activation towards M1 or M2 phenotypes. This highlights the limitations of studying the effect of different physicochemical conditions on macrophages by solely relying on conventional markers that are primarily developed to differentiate between cytokine polarized M1 and M2 macrophages. We therefore propose the adoption of unbiased screening methods in determining macrophage responses to biomaterials. Our data clearly show that the exclusive use of conventional markers and methods for determining macrophage activation status could lead to missed opportunities for understanding and exploiting macrophage responses to biomaterials.

Aptamer-Based Microfluidic Electrochemical Biosensor for Monitoring Cell-Secreted Trace Cardiac Biomarkers.

Continual monitoring of secreted biomarkers from organ-on-a-chip models is desired to understand their responses to drug exposure in a noninvasive manner. To achieve this goal, analytical methods capable of monitoring trace amounts of secreted biomarkers are of particular interest. However, a majority of existing biosensing techniques suffer from limited sensitivity, selectivity, stability, and require large working volumes, especially when cell culture medium is involved, which usually contains a plethora of nonspecific binding proteins and interfering compounds. Hence, novel analytical platforms are needed to provide noninvasive, accurate information on the status of organoids at low working volumes. Here, we report a novel microfluidic aptamer-based electrochemical biosensing platform for monitoring damage to cardiac organoids. The system is scalable, low-cost, and compatible with microfluidic platforms easing its integration with microfluidic bioreactors. To create the creatine kinase (CK)-MB biosensor, the microelectrode was functionalized with aptamers that are specific to CK-MB biomarker secreted from a damaged cardiac tissue. Compared to antibody-based sensors, the proposed aptamer-based system was highly sensitive, selective, and stable. The performance of the sensors was assessed using a heart-on-a-chip system constructed from human embryonic stem cell-derived cardiomyocytes following exposure to a cardiotoxic drug, doxorubicin. The aptamer-based biosensor was capable of measuring trace amounts of CK-MB secreted by the cardiac organoids upon drug treatments in a dose-dependent manner, which was in agreement with the beating behavior and cell viability analyses. We believe that, our microfluidic electrochemical biosensor using aptamer-based capture mechanism will find widespread applications in integration with organ-on-a-chip platforms for in situ detection of biomarkers at low abundance and high sensitivity.

Automated microfluidic platform of bead-based electrochemical immunosensor integrated with bioreactor for continual monitoring of cell secreted biomarkers.

There is an increasing interest in developing microfluidic bioreactors and organs-on-a-chip platforms combined with sensing capabilities for continual monitoring of cell-secreted biomarkers. Conventional approaches such as ELISA and mass spectroscopy cannot satisfy the needs of continual monitoring as they are labor-intensive and not easily integrable with low-volume bioreactors. This paper reports on the development of an automated microfluidic bead-based electrochemical immunosensor for in-line measurement of cell-secreted biomarkers. For the operation of the multi-use immunosensor, disposable magnetic microbeads were used to immobilize biomarker-recognition molecules. Microvalves were further integrated in the microfluidic immunosensor chip to achieve programmable operations of the immunoassay including bead loading and unloading, binding, washing, and electrochemical sensing. The platform allowed convenient integration of the immunosensor with liver-on-chips to carry out continual quantification of biomarkers secreted from hepatocytes. Transferrin and albumin productions were monitored during a 5-day hepatotoxicity assessment in which human primary hepatocytes cultured in the bioreactor were treated with acetaminophen. Taken together, our unique microfluidic immunosensor provides a new platform for in-line detection of biomarkers in low volumes and long-term in vitro assessments of cellular functions in microfluidic bioreactors and organs-on-chips.

Elastomeric free-form blood vessels for interconnecting organs on chip systems.

Conventional blood vessel-on-a-chip models are typically based on microchannel-like structures enclosed within bulk elastomers such as polydimethylsiloxane (PDMS). However, these bulk vascular models largely function as individual platforms and exhibit limited flexibility particularly when used in conjunction with other organ modules. Oftentimes, lengthy connectors and/or tubes are still needed to interface multiple chips, resulting in a large waste volume counterintuitive to the miniaturized nature of organs-on-chips. In this work, we report the development of a novel form of a vascular module based on PDMS hollow tubes, which closely emulates the morphology and properties of human blood vessels to integrate multiple organs-on-chips. Specifically, we present two templating strategies to fabricate hollow PDMS tubes with adjustable diameters and wall thicknesses, where metal rods or airflow were employed as the inner templates, while plastic tubes were used as the outer template. The PDMS tubes could then be functionalized by human umbilical vein endothelial cells (HUVECs) in their interior surfaces to further construct elastomeric biomimetic blood vessels. The endothelium developed biofunctionality as demonstrated by the expression of an endothelial biomarker (CD31) as well as dose-dependent responses in the secretion of von Willebrand factor and nitric oxide upon treatment with pharmaceutical compounds. We believe that with their clear advantages including high optical transparency, gas permeability, and tunable elasticity matching those of native blood vessels, these free-form PDMS vascular modules can supplement bulk vascular organoids and likely replace inert plastic tubes in integrating multiple organoids into a single microfluidic circuitry.

A Bioactive Carbon Nanotube-Based Ink for Printing 2D and 3D Flexible Electronics.

The development of electrically conductive carbon nanotube-based inks is reported. Using these inks, 2D and 3D structures are printed on various flexible substrates such as paper, hydrogels, and elastomers. The printed patterns have mechanical and electrical properties that make them beneficial for various biological applications.

Electrical graphene aptasensor for ultra-sensitive detection of anthrax toxin with amplified signal transduction.

Detection of the anthrax toxin, the protective antigen (PA), at the attomolar (aM) level is demonstrated by an electrical aptamer sensor based on a chemically derived graphene field-effect transistor (FET) platform. Higher affinity of the aptamer probes to PA in the aptamer-immobilized FET enables significant improvements in the limit of detection (LOD), dynamic range, and sensitivity compared to the antibody-immobilized FET. Transduction signal enhancement in the aptamer FET due to an increase in captured PA molecules results in a larger 30 mV/decade shift in the charge neutrality point (Vg,min ) as a sensitivity parameter, with the dynamic range of the PA concentration between 12 aM (LOD) and 120 fM. An additional signal enhancement is obtained by the secondary aptamer-conjugated gold nanoparticles (AuNPs-aptamer), which have a sandwich structure of aptamer/PA/aptamer-AuNPs, induce an increase in charge-doping in the graphene channel, resulting in a reduction of the LOD to 1.2 aM with a three-fold increase in the Vg,min shift.

pH sensing characteristics and biosensing application of solution-gated reduced graphene oxide field-effect transistors.

Solution-gated reduced graphene oxide field-effect transistors (R-GO FETs) were investigated for pH sensing and biochemical sensing applications. A channel of a networked R-GO film formed by self-assembly was incorporated as a sensing layer into a solution-gated FET structure for pH sensing and the detection of acetylcholine (Ach), which is a neurotransmitter in the nerve system, through enzymatic reactions. The fabricated R-GO FET was sensitive to protons (H(+)) with a pH sensitivity of 29 mV/pH in terms of the shift of the charge neutrality point (CNP), which is attributed to changes in the surface potential caused by the interaction of protons with OH surface functional groups present on the R-GO surface. The R-GO FET immobilized with acetylcholinesterase (AchE) was used to detect Ach in the concentration range of 0.1-10mM by sensing protons generated during the enzymatic reactions. The results indicate that R-GO FETs provide the capability to detect protons, demonstrating their applicability as a biosensing device for enzymatic reactions.

Reduced graphene oxide field-effect transistor for label-free femtomolar protein detection.

We report reduced graphene oxide field effect transistor (R-GO FET) biosensor for label-free ultrasensitive detection of a prostate cancer biomarker, prostate specific antigen/α1-antichymotrypsin (PSA-ACT) complex. The R-GO channel in the device was formed by reduction of graphene oxide nanosheets networked by a self-assembly process. Immunoreaction of PSA-ACT complexes with PSA monoclonal antibodies on the R-GO channel surface caused a linear response in the shift of the gate voltage, V(g,min), where the minimum conductivity occurs. The R-GO FET can detect protein-protein interactions down to femtomolar level with a dynamic range over 6-orders of magnitude in the V(g,min) shift as a sensitivity parameter. High association constants of 3.2 nM(-1) and 4.2 nM(-1) were obtained for the pH 6.2 and pH 7.4 analyte solutions, respectively. The R-GO FET biosensor showed a high specificity to other cancer biomarker in the phosphate buffered saline solutions as well as in the human serum.

Organic electrochemical transistor based immunosensor for prostate specific antigen (PSA) detection using gold nanoparticles for signal amplification.

We demonstrated a highly sensitive organic electrochemical transistor (OECT) based immunosensor with a low detection limit for prostate specific antigen/alpha1-antichymotrypsin (PSA-ACT) complex. The poly(styrenesulfonate) doped poly(3,4-ethylenedioxythiophene) (PEDOT:PSS) based OECT with secondary antibody conjugated gold nanoparticles (AuNPs) provided a detection limit of the PSA-ACT complex as low as 1pg/ml, as well as improved sensitivity and a dynamic range, due to the role of AuNPs in the signal amplification. The sensor performances were particularly improved in the lower concentration range where the detection is clinically important for the preoperative diagnosis and screening of prostate cancer. This result shows that the OECT-based immunosensor can be used as a transducer platform acceptable to the point-of-care (POC) diagnostic systems and demonstrates adaptability of organic electronics to clinical applications.