The Use of the RETeval Portable Electroretinography Device for Low-Cost Screening: A Mini-Review.

Electroretinography (ERG) provides crucial insights into retinal function and the integrity of the visual pathways. However, ERG assessments classically require a complicated technical background with costly equipment. In addition, the placement of corneal or conjunctival electrodes is not always tolerated by the patients, which restricts the measurement for pediatric evaluations. In this short review, we give an overview of the use of the RETeval portable ERG device (LKC Technologies, Inc., Gaithersburg, MD, USA), a modern portable ERG device that can facilitate screening for diseases involving the retina and the optic nerve. We also review its potential to provide ocular biomarkers in systemic pathologies, such as Alzheimer's disease and central nervous system alterations, within the framework of oculomics.

Integrating of analytical techniques with enzyme-mimicking nanomaterials for the fabrication of microfluidic systems for biomedical analysis.

Bioanalysis faces challenges in achieving fast, reliable, and point-of-care (POC) determination methods for timely diagnosis and prognosis of diseases. POC devices often display lower sensitivity compared to laboratory-based methods, limiting their ability to quantify low concentrations of target analytes. To enhance sensitivity, the synthesis of new materials and improvement of the efficiency of the analytical strategies are necessary. Enzyme-mimicking materials have revolutionized the field of the fabrication of new high-throughput sensing devices. The integration of microfluidic chips with analytical techniques offers several benefits, such as easy miniaturization, need for low biological sample volume, etc., while also enhancing the sensitivity of the probe. The use enzyme-like nanomaterials in microfluidic systems can offer portable strategies for real-time and reliable detection of biological agents. Colorimetry and electrochemical methods are commonly utilized in the fabrication of nanozyme-based microfluidic systems. The review summarizes recent developments in enzyme-mimicking materials-integrated microfluidic analytical methods in biomedical analysis and discusses the current challenges, advantages, and potential future directions.

Biomimetic Exogenous "Tissue Batteries" as Artificial Power Sources for Implantable Bioelectronic Devices Manufacturing.

Implantable bioelectronic devices (IBDs) have gained attention for their capacity to conformably detect physiological and pathological signals and further provide internal therapy. However, traditional power sources integrated into these IBDs possess intricate limitations such as bulkiness, rigidity, and biotoxicity. Recently, artificial "tissue batteries" (ATBs) have diffusely developed as artificial power sources for IBDs manufacturing, enabling comprehensive biological-activity monitoring, diagnosis, and therapy. ATBs are on-demand and designed to accommodate the soft and confining curved placement space of organisms, minimizing interface discrepancies, and providing ample power for clinical applications. This review presents the near-term advancements in ATBs, with a focus on their miniaturization, flexibility, biodegradability, and power density. Furthermore, it delves into material-screening, structural-design, and energy density across three distinct categories of TBs, distinguished by power supply strategies. These types encompass innovative energy storage devices (chemical batteries and supercapacitors), power conversion devices that harness power from human-body (biofuel cells, thermoelectric nanogenerators, bio-potential devices, piezoelectric harvesters, and triboelectric devices), and energy transfer devices that receive and utilize external energy (radiofrequency-ultrasound energy harvesters, ultrasound-induced energy harvesters, and photovoltaic devices). Ultimately, future challenges and prospects emphasize ATBs with the indispensability of bio-safety, flexibility, and high-volume energy density as crucial components in long-term implantable bioelectronic devices.

An actively stabilized, miniaturized epi-fluorescence widefield microscope for real-time observation in vivo.

Recent developments in real-time, in vivo micro-imaging have allowed for the visualization of tissue pathological changes, facilitating rapid diagnosis. However, miniaturization, magnification, the field of view, and in vivo image stabilization remain challenging factors to reconcile. A key issue for this technology is ensuring it is user friendly for surgeons, enabling them to use the device manually and obtain instantaneous information necessary for surgical decision-making. This descriptive study introduces a handheld, actively stabilized, miniaturized epi-fluorescence widefield microscope (MEW-M) for real-time observation in vivo with high resolution. The methodology of MEW-M system includes high resolution microscopy miniaturization technology, thousandfold shaking suppression (actively stabilized), ultra-photosensitivity, and tailored image signal processing cell image capture and processing technology, which support for the excellent real-time imaging performance of MEW-M system in brain, mammary, liver, lung, and kidney tissue imaging of rats in vivo. With a single-objective and high-frame-rate imaging, the MEW-M system facilitates roving image acquisition, enabling contiguous analysis of large tissue areas. RESEARCH HIGHLIGHTS: A handheld, actively stabilized MEW-M system was introduced. Excellent real-time, in vivo imaging with high resolution and active stabilization in brain, mammary, liver, lung, and kidney tissue of rats.

Emerging technologies: analytical lab vs. clinical lab perspective. Common goals and gaps to be filled in the pursuit of green and sustainable solutions.

Analytical chemistry is a broad area of science comprised of many sub-disciplines. Although each sub-discipline has its own dominant trends, one trend is common to all of them: greenness and sustainability. Efforts to develop more ecological and environmentally friendly methods have been ongoing for over a decade with initial attempts largely focusing on limiting the necessary volume of solvents required and eliminating the use of toxic solvents. Over time, the miniaturization of analytical devices gained popularity as a way of not only reducing chemical usage, but also enabling analyses using smaller sample volumes and more "remote" applications (e.g., on-site sampling and analysis). Of course, miniaturization poses numerous challenges for researchers, for instance, in relation to the method's sensitivity and reproducibility. Developments in the design of detection systems have largely helped to mitigate these issues, but they also often restrict the potential for on-site analysis. Therefore, attempts have been made to improve analysis throughout the entire analytical process, from sampling through sample preparation and instrumental analysis to data handling. Furthermore, clinical chemistry labs must adhere to certain regulations and use certified protocols and materials, which precludes the rapid implementation of solutions developed in research labs. What are the obstacles in translating such innovations to practical applications, and what inventions can make a difference in the future? The answers to these two questions define the trends in analytical chemistry in the field of medical analysis.

Development of a new miniaturized system for ultrafiltration.

Acute decompensated heart failure and fluid overload are the most common causes of hospitalization in heart failure patients, and often, they contribute to disease progression. Initial treatment encompasses intravenous diuretics although there might be a percentual of patients refractory to this pharmacological approach. New technologies have been developed to perform extracorporeal ultrafiltration in fluid overloaded patients. Current equipment allows to perform ultrafiltration in most hospital and acute care settings. Extracorporeal ultrafiltration is then prescribed and conducted by specialized teams, and fluid removal is planned to restore a status of hydration close to normal. Recent clinical trials and European and North American practice guidelines suggest that ultrafiltration is indicated for patients with refractory congestion not responding to medical therapy. Close interaction between nephrologists and cardiologists may be the key to a collaborative therapeutic effort in heart failure patients. Further studies are today suggesting that wearable technologies might become available soon to treat patients in ambulatory and de-hospitalized settings. These new technologies may help to cope with the increasing demand for the care of chronic heart failure patients. Herein, we provide a state-of-the-art review on extracorporeal ultrafiltration and describe the steps in the development of a new miniaturized system for ultrafiltration, called AD1 (Artificial Diuresis).

ANDeS: An automated nanoliter droplet selection and collection device.

The Droplet Microarray (DMA) has emerged as a tool for high-throughput biological and chemical applications by enabling miniaturization and parallelization of experimental processes. Due to its ability to hold hundreds of nanoliter droplets, the DMA enables simple screening and analysis of samples such as cells and biomolecules. However, handling of nanoliter volumes poses a challenge, as manual recovery of nanoliter volumes is not feasible, and traditional laboratory equipment is not suited to work with such low volumes, and small array formats. To tackle this challenge, we developed the Automated Nanoliter Droplet Selection device (ANDeS), a robotic system for automated collection and transfer of nanoliter samples from DMA. ANDeS can automatically collect volumes from 50 to 350 nL from the flat surface of DMA with a movement accuracy of ±30 µm using fused silica capillaries. The system can automatically collect and transfer the droplets from DMA chip into other platforms, such as microtiter plates, conical tubes or another DMA. In addition, to ensure high throughput and multiple droplet collection, the uptake of multiple droplets within a single capillary, separated by air gaps to avoid mixing of the samples within the capillary, was optimized and demonstrated. This study shows the potential of ANDeS in laboratory applications by using it for the collection and transfer of biological samples, contained in nanoliter droplets, for subsequent analysis. The experimental results demonstrate the ability of ANDeS to increase the versatility of the DMA platform by allowing for automated retrieval of nanoliter samples from DMA, which was not possible manually on the level of individual droplets. Therefore, it widens the variety of analytical techniques that can be used for the analysis of content of individual droplets and experiments performed using DMA. Thus, ANDeS opens up opportunities to expand the development of miniaturized assays in such fields as cell screening, omics analysis and combinatorial chemistry.

Miniaturization of an enclosed electrospinning process to enhance reproducibility in the fabrication of rapidly dissolving cell-based biosensors.

There is broad interest in producing electrospun films embedded with biological materials. It is well known that electrospinning requires careful control of the process conditions, especially the environmental conditions such as relative humidity (RH). Given that commercial electrospinning systems are expensive (> $10,000) and are typically too large to be used in standard biological safety cabinets (BSC), we designed and built a miniaturized electrospinning box (E-Box) that will fit inside a BSC, and the RH can be easily controlled using simple instrumentation (gas cylinder, regulator, needle valve, rotameter). It uses an inexpensive computerized numerical control machine to control the spinneret positioning and collector rotational speed-all the parts for the device (except the syringe pump and voltage supply) can be purchased for approximately $1000. We demonstrate the usefulness of our design in optimizing the production of Escherichia coli-embedded pullulan-trehalose films to be used as rapidly dissolving biosensors for environmental monitoring. At a fixed electrospinning recipe, we showed that decreasing the RH from approximately 48% to 22% resulted in the average fiber diameter increasing from 240 (± 11) nm to 314 (± 8) nm. We also demonstrate the usefulness of our design in performing sequential electrospinning experiments to evaluate process performance reproducibility. For example, from just 1 mL of a polymer solution, we produced 16 electrospun films (approximately 3 cm by 8 cm each)-from those films we hole-punched approximately 80 biosensor discs which were then used in subsequent experiments to determine the amount of two different biocides (Grotan BK and triclosan) in aqueous samples. The technique developed in this study is ideal for creating electrospun materials in high quantities that are highly reproducible through the precise control of RH.

Miniaturization of flexible ureteroscopes: a comparative trend analysis of 59 flexible ureteroscopes.

The purpose of this review is to analyze the trend in miniaturization of flexible ureteroscopes over the past decades, identify the advantages and disadvantages, and determine the correlation of individual parameters with release period. Flexible ureteroscopes mentioned in the literature or those commercially available were searched. To minimize the search bias, the instruments were grouped by release date time periods of < 2000 year, 2000-2009, 2010-2019, and 2020 onwards. The final review included only those instrument models for which data on tip size, overall shaft, working length and channel size had been determined. The correlation among features investigated as well as with release period was also determined. 59 models of flexible ureteroscopes (26 fiber optic and 33 digital scopes) were included. Among the different features investigated among fiber optic endoscopes, only the sizes of the distal tip and overall shaft positively correlated with each other. In contrast to their fiber optic counterparts, a strong positive correlation was observed between tip and channel sizes, whereas negative correlation was found between channel size and overall shaft size and working length of digital scopes. Only distal tip of fiber optic flexible ureteroscopes and overall shaft of digital endoscopes were significantly reduced over their evolution. With the development of technology, there has been an improvement of flexible ureteroscopes and one of the indicators of this trend is a decrease in their size. With a definite trend towards miniaturization over the past decades, a significant correlation was observed in tip size and overall shaft for fiber optic and digital endoscopes, respectively.

Development of antibacterial neural stimulation electrodes via hierarchical surface restructuring and atomic layer deposition.

Miniaturization and electrochemical performance enhancement of electrodes and microelectrode arrays in emerging long-term implantable neural stimulation devices improves specificity, functionality, and performance of these devices. However, surgical site and post-implantation infections are amongst the most devastating complications after surgical procedures and implantations. Additionally, with the increased use of antibiotics, the threat of antibiotic resistance is significant and is increasingly being recognized as a global problem. Therefore, the need for alternative strategies to eliminate post-implantation infections and reduce antibiotic use has led to the development of medical devices with antibacterial properties. In this work, we report on the development of electrochemically active antibacterial platinum-iridium electrodes targeted for use in neural stimulation and sensing applications. A two-step development process was used. Electrodes were first restructured using femtosecond laser hierarchical surface restructuring. In the second step of the process, atomic layer deposition was utilized to deposit conformal antibacterial copper oxide thin films on the hierarchical surface structure of the electrodes to impart antibacterial properties to the electrodes with minimal impact on electrochemical performance of the electrodes. Morphological, compositional, and structural properties of the electrodes were studied using multiple modalities of microscopy and spectroscopy. Antibacterial properties of the electrodes were also studied, particularly, the killing effect of the hierarchically restructured antibacterial electrodes on Escherichia coli and Staphylococcus aureus-two common types of bacteria responsible for implant infections.

Miniature battery-free bioelectronics.

Miniature wireless bioelectronic implants that can operate for extended periods of time can transform how we treat disorders by acting rapidly on precise nerves and organs in a way that drugs cannot. To reach this goal, materials and methods are needed to wirelessly transfer energy through the body or harvest energy from the body itself. We review some of the capabilities of emerging energy transfer methods to identify the performance envelope for existing technology and discover where opportunities lie to improve how much-and how efficiently-we can deliver energy to the tiny bioelectronic implants that can support emerging medical technologies.

Miniaturization does not change conserved spider anatomy, a case study on spider Rayforstia (Araneae: Anapidae).

Miniaturization is an evolutionary trend observed in many animals. Some arachnid groups, such as spiders and mites, demonstrate a strong tendency toward miniaturization. Some of the most miniaturized spiders belong to the family Anapidae. In this study, using light and confocal microscopy and 3D modelling, we provide the first detailed description of the anatomy of a spider of the genus Rayforstia, which is only 900 µm long. In comparison with larger spiders, Rayforstia has no branching of the midgut in the prosoma and an increased relative brain volume. In contrast to many miniature insects and mites, the spider shows no reduction of whole organ systems, no allometry of the digestive and reproductive systems, and also no reduction of the set of muscles. Thus, miniature spider shows a more conserved anatomy than insects of a similar size. These findings expand our knowledge of miniaturization in terrestrial arthropods.

A strategy for Cas13 miniaturization based on the structure and AlphaFold.

The small size of the Cas nuclease fused with various effector domains enables a broad range of function. Although there are several ways of reducing the size of the Cas nuclease complex, no efficient or generalizable method has been demonstrated to achieve protein miniaturization. In this study, we establish an Interaction, Dynamics and Conservation (IDC) strategy for protein miniaturization and generate five compact variants of Cas13 with full RNA binding and cleavage activity comparable the wild-type enzymes based on a combination of IDC strategy and AlphaFold2. In addition, we construct an RNA base editor, mini-Vx, and a single AAV (adeno-associated virus) carrying a mini-RfxCas13d and crRNA expression cassette, which individually shows efficient conversion rate and RNA-knockdown activity. In summary, these findings highlight a feasible strategy for generating downsized CRISPR/Cas13 systems based on structure predicted by AlphaFold2, enabling targeted degradation of RNAs and RNA editing for basic research and therapeutic applications.

Implantable microfluidics: methods and applications.

Implantable microfluidics involves integrating microfluidic functionalities into implantable devices, such as medical implants or bioelectronic devices, revolutionizing healthcare by enabling personalized and precise diagnostics, targeted drug delivery, and regeneration of targeted tissues or organs. The impact of implantable microfluidics depends heavily on advancements in both methods and applications. Despite significant progress in the past two decades, continuous advancements are still required in fluidic control and manipulation, device miniaturization and integration, biosafety considerations, as well as the development of various application scenarios to address a wide range of healthcare issues. In this review, we discuss advancements in implantable microfluidics, focusing on methods and applications. Regarding methods, we discuss progress made in fluid manipulation, device fabrication, and biosafety considerations in implantable microfluidics. In terms of applications, we review advancements in using implantable microfluidics for drug delivery, diagnostics, tissue engineering, and energy harvesting. The purpose of this review is to expand research ideas for the development of novel implantable microfluidic devices for various healthcare applications.

Affordable, accurate and unbiased RNA sequencing by manual library miniaturization: A case study in barley.

We present an easy-to-reproduce manual miniaturized full-length RNA sequencing (RNAseq) library preparation workflow that does not require the upfront investment in expensive lab equipment or long setup times. With minimal adjustments to an established commercial protocol, we were able to manually miniaturize the RNAseq library preparation by a factor of up to 1:8. This led to cost savings for miniaturized library preparation of up to 86.1% compared to the gold standard. The resulting data were the basis of a rigorous quality control analysis that inspected: sequencing quality metrics, gene body coverage, raw read duplications, alignment statistics, read pair duplications, detected transcripts and sequence variants. We also included a deep dive data analysis identifying rRNA contamination and suggested ways to circumvent these. In the end, we could not find any indication of biases or inaccuracies caused by the RNAseq library miniaturization. The variance in detected transcripts was minimal and not influenced by the miniaturization level. Our results suggest that the workflow is highly reproducible and the sequence data suitable for downstream analyses such as differential gene expression analysis or variant calling.

Miniaturization and Automation Protocol of a Urinary Organic Acid Liquid-Liquid Extraction Method on GC-MS.

The aim of this study was to improve the extraction method for urinary organic acids by miniaturizing and automating the process. Currently, manual extraction methods are commonly used, which can be time-consuming and lead to variations in test results. To address these issues, we reassessed and miniaturized the in-house extraction method, reducing the number of steps and the sample-to-solvent volumes required. The evaluated miniaturized method was translated into an automated extraction procedure on a MicroLab (ML) Star (Hamilton Technologies) liquid handler. This was then validated using samples obtained from the ERNDIM External Quality Assurance program. The organic acid extraction method was successfully miniaturized and automated using the Autosampler robot. The linear range for most of the thirteen standard analytes fell between 0 to 300 mg/L in spiked synthetic urine, with low (50 mg/L), medium (100 mg/L), and high (500 mg/L) levels. The correlation coefficient (r) for most analytes was >0.99, indicating a strong relationship between the measured values. Furthermore, the automated extraction method demonstrated acceptable precision, as most organic acids had coefficients of variation (CVs) below 20%. In conclusion, the automated extraction method provided comparable or even superior results compared to the current in-house method. It has the potential to reduce solvent volumes used during extraction, increase sample throughput, and minimize variability and random errors in routine diagnostic settings.

Expansion of the Analytical Modeling of Capacitance for 1-N-1 Multilayered CID Structures with Monotonically Increasing/Decreasing Permittivity.

Capacitive sensors that utilize the Coplanar Interdigitated (CID) electrode structure are widely employed in various technical and analytical domains, such as healthcare, infectious disease management, pharmaceuticals, metrology, and environmental monitoring. The present exigency for lab-on-a-chip contrivances and the requisite for the miniaturization of sensors have led to the widespread adoption of CID sensors featuring multiple dielectric layers (DLs), either in the form of substrates or superstrates. Previously, we derived an analytical model for the capacitance of CID capacitive sensors with four distinct 1-N-1 patterns (namely, 1-1-1, 1-3-1, 1-5-1, and 1-11-1) using partial capacitance (PC) and conformal mapping (CM) techniques. The aforementioned model has been employed in various applications wherein the permittivity of successive layers exhibits a monotonic decrease as one moves away from the electrode plane, resulting in highly satisfactory outcomes. Nevertheless, the PC technique is inadequate for structures with multiple layers where the permittivity exhibits a monotonic increase as the distance from the electrodes increases. Given these circumstances, it is necessary to adapt the initial PC method to incorporate these novel configurations. In this work, we have discussed a new approach, splitting the concept of PC into partial parallel capacitance (PPC) and partial serial capacitance (PSC), where new CM transformations are proposed for the latter case. Thus, the present study proposes a novel methodology to expand upon our prior analytical framework, which aims to incorporate scenarios where the permittivity experiences a reduction across successive layers. The outcomes are juxtaposed with the finite element simulation and analytical findings.

Submillimeter Multifunctional Ferromagnetic Fiber Robots for Navigation, Sensing, and Modulation.

Small-scale robots capable of remote active steering and navigation offer great potential for biomedical applications. However, the current design and manufacturing procedure impede their miniaturization and integration of various diagnostic and therapeutic functionalities. Herein, submillimeter fiber robots that can integrate navigation, sensing, and modulation functions are presented. These fiber robots are fabricated through a scalable thermal drawing process at a speed of 4 meters per minute, which enables the integration of ferromagnetic, electrical, optical, and microfluidic composite with an overall diameter of as small as 250 µm and a length of as long as 150 m. The fiber tip deflection angle can reach up to 54o under a uniform magnetic field of 45 mT. These fiber robots can navigate through complex and constrained environments, such as artificial vessels and brain phantoms. Moreover, Langendorff mouse hearts model, glioblastoma micro platforms, and in vivo mouse models are utilized to demonstrate the capabilities of sensing electrophysiology signals and performing a localized treatment. Additionally, it is demonstrated that the fiber robots can serve as endoscopes with embedded waveguides. These fiber robots provide a versatile platform for targeted multimodal detection and treatment at hard-to-reach locations in a minimally invasive and remotely controllable manner.

Characterization of the electrocardiogram of microminipig in comparison with that of Clawn miniature swine: impacts of miniaturization of body size on electrocardiographic indices.

Effects of body size reduction on electrocardiographic indices were examined using microminipigs in comparison with Clawn miniature swine (Clawn). Electrocardiogram was recorded using Holter electrocardiograph in conscious state for 24 hr for microminipigs (male: 11.6 ± 0.1 kg, 12-17 months, n=5; and female: 9.9 ± 0.4 kg, 6 months, n=5) and Clawn (female: 20.3 ± 0.4 kg, 8-9 months, n=8). Microminipig had shorter PR interval and QRS width than Clawn, whereas no significant difference was detected in JTcF/QTcF between them. Ratios of PR interval, QRS width, and body weight cubic root for microminipigs to Clawn ranged between 0.713 and 0.830. These findings indicate that PR interval and QRS width will depend on distance for excitatory current propagation, whereas JTcF/QTcF may be governed by local electrical activities.

Enhanced magnetic modulation of surface plasmon polaritons on hyperbolic metasurfaces.

In this Letter we demonstrate a fundamentally new, to the best of our knowledge, concept to enhance the magnetic modulation of the surface plasmon polaritons (SPPs) by using hybrid magneto-plasmonic structures consisting of hyperbolic plasmonic metasurfaces and magnetic dielectric substrates. Our results show that the magnetic modulation of SPPs in the proposed structures can be an order of magnitude stronger than in the hybrid metal-ferromagnet multilayer structures conventionally used in active magneto-plasmonics. We believe that this effect will allow for the further miniaturization of magneto-plasmonic devices.