Microfluidics for nano-drug delivery systems: from fundamentals to industrialization

In recent years, owing to the miniaturization of the fluidic environment, microfluidic technology offers unique opportunities for the implementation of nano drug delivery systems (NDDSs) production processes. Compared with traditional methods, microfluidics improves the controllability and uniformity of NDDSs. The fast mixing and laminar flow properties achieved in the microchannels can tune the physicochemical properties of NDDSs, including particle size, distribution and morphology, resulting in narrow particle size distribution and high drug-loading capacity. The success of lipid nanoparticles encapsulated mRNA vaccines against coronavirus disease 2019 by microfluidics also confirmed its feasibility for scaling up the preparation of NDDSs via parallelization or numbering-up. In this review, we provide a comprehensive summary of microfluidics-based NDDSs, including the fundamentals of microfluidics, microfluidic synthesis of NDDSs, and their industrialization. The challenges of microfluidics-based NDDSs in the current status and the prospects for future development are also discussed. We believe that this review will provide good guidance for microfluidics-based NDDSs.Copyright © 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences

Thoracic ultrasound.

Ultrasound is an imaging technique based on the interaction of ultrasound with biological tissues, generated and received by a probe and processed by an ultrasound scanner into a two-dimensional image. Available ultrasound equipment is not designed to study lung paren-chyma, which due to its physical characteristics completely reflects the ultrasound, generating an artefactual picture. However, the presence of pathological conditions affecting the pleura and parenchyma unveils the organ, allowing an accurate study of superficial pathological changes and finding application in the pathology of the chest wall, pleura, lung parenchyma and in the study of diaphragmatic dynamics, adapting itself to multiple clinical contexts. Technological evolution and miniaturization have undoubtedly helped the method to spread widely, also helped by the COVID-19 pandemic. Artificial intelligence technologies are currently being studied to improve the diagnostic yield by supporting operators in interpreting pathological pictures, but the production of images of good quality remains a limit.Copyright © by Associazione Italiana Pneumologi Ospeda-lieri - Italian Thoracic Society (AIPO - ITS).

Present status of microfluidic PCR chip in nucleic acid detection and future perspective

Polymerase chain reaction (PCR) amplifies specific fragment of DNA molecules and has been extensively applied in fields of pathogens and gene mutation detection, food safety and clinical diagnosis which on the other hand, holds the drawbacks of large size instrument, high heat dissipation etc. It has been demonstrated that microfluidics technique coupling with PCR reaction exhibits characteristics of integration, automatization, miniaturization, and portability. Meanwhile, various designed fabrication of microchip could contribute to diverse applications. In this review, we summarized major works about a variety of microfluidic chips equipped with several kinds of PCR techniques (PCR, RT-PCR, mPCR, dPCR) and detection methods like fluorescence, electrochemistry, and electrophoresis detection. The development and application of PCR-based microfluidic chip in pathogen and gene mutation detection, diseases prevention and diagnosis, DNA hybridization and low-volume sample treatment were also discussed. Copyright © 2022 Elsevier B.V.

Engineering Design, Implementation, and Sensing Mechanisms of Wearable Bioelectronic Sensors in Clinical Settings

Wearable sensing devices have transformed the hourly analysis of events such as body signals and environmental risks into real‐time monitoring in minutes or seconds. Wearable sensors have facilitated the ability to obtain useful data by monitoring the physiological parameters and activities of an aided and a healthy individual. Wearable devices employ detectable biomarkers in the human body, such as in tears, saliva, interstitial fluid, sweat, and so on. These can deliver relevant information on human health, online activity monitoring, and therapeutic treatments. This section outlines the significance of sample types and associated biomarkers as indicators in the development and manufacturing of wearable biosensors. We have emphasized the most recent advances of wearables based on skin‐like and textile, giving attention to personalized health monitoring to record signals of motion and physiological and body fluid investigation. Furthermore, this review categorizes wearable biosensors based on the sensing mechanism, electrochemical, optical, and mechanical. Additionally, the recent wearables related to the detection of the newly havoc‐causing pandemic, COVID‐19, and the future perspective for the development of much more advanced and potent wearable biosensors have been highlighted. The final section highlights unmet difficulties and gaps in wearable sensors in personalized therapy. [ FROM AUTHOR]

The Unaccounted Morbidity of Covid 19 Pandemic: A Tertiary Level Center's Assessment of Impact of Pandemic on Urolithiasis Patients

Introduction &Objective: Severe acute respiratory syndrome coronavirus 2 causes coronavirus disease 2019 (COVID-19). Since March 2020, this pandemic has caused unprecedented human suffering. With limiting medical services available and prolonged neglect, patients with urolithiasis have seen significant increase in morbidity during this pandemic. Method(s): The study was conducted at a tertiary level apex medical centre of north India from November 2020 to July 2021. Patients who were diagnosed with urolithiasis before March 2020 but could not receive timely management due to pandemic situations were enrolled for study. Result(s): The study included 91 patients(53-male, 38-female) with mean age of 40.3 +/- 13.2 (18-65) years. Among these 83 patients had urolithiasis whereas 8 patients had encrusted DJS. Sixty four (70.3%) patients had primary stones whereas 21 (23.1%) had recurrent stones. Proposed management at initial assessment of these patients pre-pandemic was Medical (5), ESWL (38), URSL (17), RIRS (5), DJR (8) and PCNL (18). The mean (range) stone size (n = 83) pre pandemic was 13.8 +/- 8.43 (5-55) mm and at the time of final management due to pandemic delay was 19.1 +/- 10.1 (6-60) mm. This translates into a mean increase of stone size of 5.3 +/- 5.7 (0-35) mm. Mean (range) delay in management of these patients was found to be 11.2 +/- 5.8 (9-15) months. Thirty-two patients required change in management due to delay as a result of Covid pandemic. Despite restrictions during the pandemic, a total of 19 patients had to visit emergency department out of which 7 patients required percutaneous nephrostomy (PCN) placement. Among seven patients undergoing PCN placement, 3 had accidental slippage of PCN which required additional emergency department visit for PCN re-placement. Two patients who were planned for URSL at initial presentation with stone sizes of 8mm and 7mm in the lower ureter passed their stone spontaneously with self-continued medical expulsive therapy During the pandemic imposed restrictions, 8 patients presented with encrusted stents and underwent URSL in 5, CLT in 2 and URSL,CLT with PCNL in 1 patient for stent removal. Conclusion(s): Effect of Covid 19 pandemic on urolithiasis has been immense. Urolithiasis patients need to be carefully evaluated and in presence of complications or loss of renal function early intervention should be offered. Role of non ot procedures like ESWL, DJ stenting, PCN insertion have to be given importance beyond traditional practices. Surgical interventions providing maximal clearance in least attempts should be chosen over miniaturization.

A self-assembling split aptamer multiplex assay for SARS-COVID19 and miniaturization of a malachite green DNA-based aptamer.

Multiplex assays often rely on expensive sensors incorporating covalently linked fluorescent dyes. Herein, we developed a self-assembling aptamer-based multiplex assay. This multiplex approach utilizes a previously established split aptamer sensor in conjugation with a novel split aptamer sensor based upon a malachite green DNA aptamer. This system was capable of simultaneous fluorescent detection of two SARS COVID-19-related sequences in one sample with individual sensors that possesses a limit of detection (LOD) in the low nM range. Optimization of the Split Malachite Green (SMG) sensor yielded a minimized aptamer construct, Mini-MG, capable of inducing fluorescence of malachite green in both a DNA hairpin and sensor format.

Identification of potent inhibitors of SARS-CoV-2 exoribonuclease by fluorescence polarization assay

The emergence of SARS-CoV-2 has triggered a pandemic with devastating consequences to the world. One of the proteins essential to the virus life cycle is nsp14, which is a bifunctional protein that encodes a 3'to 5' exoribonuclease activity in its N-terminus, and a methyl transferase activity in its C-terminus. Nsp14 in complex with the accessory protein nsp10 is involved in a proofreading mechanism that ensures the genetic stability of its massive viral genome, and is associated to the resistance against nucleotide analogs targeting the polymerase nsp12. Because of its key role, nsp14-nsp10 complex constitutes an attractive target for antiviral development. Here we present a fluorescence polarization (FP) assay development to measure the exoribonuclease activity and its inhibition in vitro. The FP method is sensitive, robust, amenable to miniaturization and offers confirmation by visualizing the degradation of the fluorescent RNA in acrylamide gels. We performed a screening of a focused library of 113 metal chelators at 20 and 5 μM compound concentration and IC50 measurement of 9 hits showing efficiency at micromolar level. We also tested the focused library in SARS-CoV-2 infected Vero cells and we confirmed 3 hits previously detected in the in vitro screening out of 6 promising inhibitors. In conclusion the FP method proposed is a reliable tool to discover inhibitors of the SARS-CoV-2 exoribonuclease activity and will help to find new antivirals to be used in combination with nucleoside analogs.

Engineering Design, Implementation, and Sensing Mechanisms of Wearable Bioelectronic Sensors in Clinical Settings

Wearable sensing devices have transformed the hourly analysis of events such as body signals and environmental risks into real-time monitoring in minutes or seconds. Wearable sensors have facilitated the ability to obtain useful data by monitoring the physiological parameters and activities of an aided and a healthy individual. Wearable devices employ detectable biomarkers in the human body, such as in tears, saliva, interstitial fluid, sweat, and so on. These can deliver relevant information on human health, online activity monitoring, and therapeutic treatments. This section outlines the significance of sample types and associated biomarkers as indicators in the development and manufacturing of wearable biosensors. We have emphasized the most recent advances of wearables based on skin-like and textile, giving attention to personalized health monitoring to record signals of motion and physiological and body fluid investigation. Furthermore, this review categorizes wearable biosensors based on the sensing mechanism, electrochemical, optical, and mechanical. Additionally, the recent wearables related to the detection of the newly havoc-causing pandemic, COVID-19, and the future perspective for the development of much more advanced and potent wearable biosensors have been highlighted. The final section highlights unmet difficulties and gaps in wearable sensors in personalized therapy. © 2022 Wiley-VCH GmbH.

What's Next For Wearable Sensing?

The commercial explosion of wearable sensing devices in the early 2010s forever changed the landscape of wearable computing. In a few short years, wrist-mounted devices such as wristbands and smart watches dominated the market.1 In 2017, this department featured an article titled “What will we wear after smartphones?” highlighting potential pathways for wearable computing as the early enthusiasm for commercial wearable sensors began to wane, and new form factors like on-skin devices gained traction in the research community.2 In the past few years, we have witnessed substantial changes in many of the domains discussed in that article. Sensor validation and comparison with other state of the art or reference systems has become of paramount importance in a saturated wearables market. Similarly, FDA approval or CE marking of smartphone or sensor-based medical applications is now a priority of many of the players targeting healthcare applications. For traditional form factors such as wristbands and other accessories, large improvements have also been made in hardware, thanks to further miniaturization and improved design (see Figure 1). Figure 1. Phone cameras, watches, and rings have become widespread sensing modalities for accurate monitoring of biometric data. Figure 2. Graphs show mean deviation from baseline (lines) with 95% CIs (shaded areas) for daily resting heart rate (RHR), sleep quantity, and step count during −7 to 133 days after symptom onset for COVID-19–positive versus COVID-19–negative participants (panels (a), (c), and (e)) and for COVID-19–positive participants grouped by mean change in RHR during days 28 to 56 after symptom onset (panels (b), (d), and (f)). Acquired with permission from Radin et al.8

Low Volume in Vitro Diagnostic Proton NMR Spectroscopy of Human Blood Plasma for Lipoprotein and Metabolite Analysis: Application to SARS-CoV-2 Biomarkers.

The utility of low sample volume in vitro diagnostic (IVDr) proton nuclear magnetic resonance (1H NMR) spectroscopic experiments on blood plasma for information recovery from limited availability or high value samples was exemplified using plasma from patients with SARS-CoV-2 infection and normal controls. 1H NMR spectra were obtained using solvent-suppressed 1D, spin-echo (CPMG), and 2-dimensional J-resolved (JRES) spectroscopy using both 3 mm outer diameter SampleJet NMR tubes (100 µL plasma) and 5 mm SampleJet NMR tubes (300 µL plasma) under in vitro diagnostic conditions. We noted near identical diagnostic models in both standard and low volume IVDr lipoprotein analysis (measuring 112 lipoprotein parameters) with a comparison of the two tubes yielding R2 values ranging between 0.82 and 0.99 for the 40 paired lipoprotein parameters samples. Lipoprotein measurements for the 3 mm tubes were achieved without time penalty over the 5 mm tubes as defined by biomarker recovery for SARS-CoV-2. Overall, biomarker pattern recovery for the lipoproteins was extremely similar, but there were some small positive offsets in the linear equations for several variables due to small shimming artifacts, but there was minimal degradation of the biological information. For the standard untargeted 1D, CPMG, and JRES NMR experiments on the same samples, the reduced signal-to-noise was more constraining and required greater scanning times to achieve similar differential diagnostic performance (15 min per sample per experiment for 3 mm 1D and CPMG, compared to 4 min for the 5 mm tubes). We conclude that the 3 mm IVDr method is fit-for-purpose for quantitative lipoprotein measurements, allowing the preparation of smaller volumes for high value or limited volume samples that is common in clinical studies. If there are no analytical time constraints, the lower volume experiments are equally informative for untargeted profiling.

Recent Development in Micromanufacturing of Metallic Materials.

Product miniaturization is a trend for facilitating product usage, enabling product functions to be implemented in microscale geometries, and aimed at reducing product weight, volume, cost and pollution. Driven by ongoing miniaturization in diverse areas including medical devices, precision equipment, communication devices, micro-electromechanical systems (MEMS) and microsystems technology (MST), the demands for micro metallic products have increased tremendously. Such a trend requires development of advanced micromanufacturing technology of metallic materials for producing high-quality micro metallic products that possess excellent dimensional tolerances, required mechanical properties and improved surface quality. Micromanufacturing differs from conventional manufacturing technology in terms of materials, processes, tools, and machines and equipment, due to the miniaturization nature of the whole micromanufacturing system, which challenges the rapid development of micromanufacturing technology. Against such a background, the Special Issue "Micromanufacturing of Metallic Materials" was proposed to present the recent developments of micromanufacturing technologies of metallic materials. The papers collected in the Special Issue include research articles, literature review and technical notes, which have been highlighted in this editorial.micromanufacturing; metallic materials; miniaturization; micro products.

The vision of point-of-care PCR tests for the COVID-19 pandemic and beyond.

Infectious diseases, such as the most recent case of coronavirus disease 2019, have brought the prospect of point-of-care (POC) diagnostic tests into the spotlight. A rapid, accurate, low-cost, and easy-to-use test in the field could stop epidemics before they develop into full-blown pandemics. Unfortunately, despite all the advances, it still does not exist. Here, we critically review the limited number of prototypes demonstrated to date that is based on a polymerase chain reaction (PCR) and has come close to fulfill this vision. We summarize the requirements for the POC-PCR tests and then go on to discuss the PCR product-detection methods, the integration of their functional components, the potential applications, and other practical issues related to the implementation of lab-on-a-chip technologies. We conclude our review with a discussion of the latest findings on nucleic acid-based diagnosis.