{"title":"A portable point-of-care testing device for forward blood typing with hemophilia diagnosis","authors":"Yaw-Jen Chang, Shang-Fen Yeh, Pin-Jyun Chen","doi":"10.1007/s10544-023-00678-8","DOIUrl":"10.1007/s10544-023-00678-8","url":null,"abstract":"<div><p>This paper presents a portable point-of-care testing (POCT) device to conduct simultaneous and on-site tests of ABO and Rh(D) forward blood typing and hemophilia diagnosis using only a small amount of human whole blood sample. The POCT device consisted of a spinning module, a measuring circuit, an interdigitated electrode (IDE) for hemophilia diagnosis, and three disposable microfluidic chips for bioassays with anti-A, anti-B, and anti-D, respectively, and measurement of the concentration of factor VIII. Agglutination will occur if red blood cells (RBCs) are exposed to the corresponding antibody. To evaluate the degree of RBC agglutination, a linear sweep voltage, ranging from − 0.5 to + 0.5 V, was applied to the electrodes of the microfluidic chip and the resulting current was measured. For different levels of agglutination, the measured I–V curves were explicitly discriminated, providing five clinical levels from non-agglutination (level 0) to strong agglutination (level 4). The quantitative norm obtained from cubic fitting function of each I–V curve served as the criterion to represent this agglutination level. The ABO blood type was determined by both agglutination levels of the blood sample reacting with anti-A and anti-B. The degree of agglutination with anti-D gave the Rh(D) type. Moreover, the concentration of factor VIII was detected for the determination of hemophilia. Without requiring expensive equipment, this POCT device is especially suitable for usage in emergency or natural disasters to provide quantitative testing in rescue and relief operations.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41100069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Satoru Kawakita, Shaopei Li, Huu Tuan Nguyen, Surjendu Maity, Reihaneh Haghniaz, Jamal Bahari, Ning Yu, Kalpana Mandal, Praveen Bandaru, Lei Mou, Menekse Ermis, Enam Khalil, Safoora Khosravi, Arne Peirsman, Rohollah Nasiri, Annie Adachi, Aya Nakayama, Remy Bell, Yangzhi Zhu, Vadim Jucaud, Mehmet Remzi Dokmeci, Ali Khademhosseini
{"title":"Rapid integration of screen-printed electrodes into thermoplastic organ-on-a-chip devices for real-time monitoring of trans-endothelial electrical resistance","authors":"Satoru Kawakita, Shaopei Li, Huu Tuan Nguyen, Surjendu Maity, Reihaneh Haghniaz, Jamal Bahari, Ning Yu, Kalpana Mandal, Praveen Bandaru, Lei Mou, Menekse Ermis, Enam Khalil, Safoora Khosravi, Arne Peirsman, Rohollah Nasiri, Annie Adachi, Aya Nakayama, Remy Bell, Yangzhi Zhu, Vadim Jucaud, Mehmet Remzi Dokmeci, Ali Khademhosseini","doi":"10.1007/s10544-023-00669-9","DOIUrl":"10.1007/s10544-023-00669-9","url":null,"abstract":"<div><p>Trans-endothelial electrical resistance (TEER) is one of the most widely used indicators to quantify the barrier integrity of endothelial layers. Over the last decade, the integration of TEER sensors into organ-on-a-chip (OOC) platforms has gained increasing interest for its efficient and effective measurement of TEER in OOCs. To date, microfabricated electrodes or direct insertion of wires has been used to integrate TEER sensors into OOCs, with each method having advantages and disadvantages. In this study, we developed a TEER-SPE chip consisting of carbon-based screen-printed electrodes (SPEs) embedded in a poly(methyl methacrylate) (PMMA)-based multi-layered microfluidic device with a porous poly(ethylene terephthalate) membrane in-between. As proof of concept, we demonstrated the successful cultures of hCMEC/D3 cells and the formation of confluent monolayers in the TEER-SPE chip and obtained TEER measurements for 4 days. Additionally, the TEER-SPE chip could detect changes in the barrier integrity due to shear stress or an inflammatory cytokine (i.e., tumor necrosis factor-α). The novel approach enables a low-cost and facile fabrication of carbon-based SPEs on PMMA substrates and the subsequent assembly of PMMA layers for rapid prototyping. Being cost-effective and cleanroom-free, our method lowers the existing logistical and technical barriers presenting itself as another step forward to the broader adoption of OOCs with TEER measurement capability.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41095682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicolas Mytzka, Skaiste Arbaciauskaite, Natalia Sandetskaya, Kai Mattern, Dirk Kuhlmeier
{"title":"A fully integrated duplex RT-LAMP device for the detection of viral infections","authors":"Nicolas Mytzka, Skaiste Arbaciauskaite, Natalia Sandetskaya, Kai Mattern, Dirk Kuhlmeier","doi":"10.1007/s10544-023-00676-w","DOIUrl":"10.1007/s10544-023-00676-w","url":null,"abstract":"<div><p>Respiratory viruses can cause epidemics or pandemics, which are worldwide outbreaks of disease. The severity of these events varies depending on the virus, its characteristics, along with environmental factors. The frequency of epidemics and pandemics caused by respiratory viruses is difficult to predict, but the potential severity of such events underlines the importance of continued monitoring, research, and preparation for emerging infectious diseases. To help improve pandemic preparedness, we created a fully integrated duplex reverse transcription loop-mediated isothermal amplification (RT-LAMP) device targeting two respiratory viruses, influenza A/X-31 virus and bovine coronavirus, as a replacement for SARS-CoV-2. This device can be adapted to any other respiratory virus. In this study, we showed and evaluated a prototype of a microfluidic system, and showed that duplex RT-LAMP can detect and distinguish between the two viruses, with LoDs of 2,000 copies/ml for bovine coronavirus and 200 copies/ml for influenza A/X-31 virus.</p><h3>Graphical abstract</h3>\u0000 <figure><div><div><div><picture><source><img></source></picture></div></div></div></figure>\u0000 </div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00676-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6551732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Domenic Pascual, Lisa Brauns, Ruth Domes, Matthias Tisler, Marco Kögel, Angelika Stumpf, Andreas Kirschniak, Jens Rolinger, Udo Kraushaar, Peter D. Jones
{"title":"A flexible implant for acute intrapancreatic electrophysiology","authors":"Domenic Pascual, Lisa Brauns, Ruth Domes, Matthias Tisler, Marco Kögel, Angelika Stumpf, Andreas Kirschniak, Jens Rolinger, Udo Kraushaar, Peter D. Jones","doi":"10.1007/s10544-023-00662-2","DOIUrl":"10.1007/s10544-023-00662-2","url":null,"abstract":"<div><p>Microelectrode arrays (MEAs) have proven to be a powerful tool to study electrophysiological processes over the last decades with most technology developed for investigation of the heart or brain. Other targets in the field of bioelectronic medicine are the peripheral nervous system and its innervation of various organs. Beyond the heart and nervous systems, the beta cells of the pancreatic islets of Langerhans generate action potentials during the production of insulin. <i>In vitro</i> experiments have demonstrated that their activity is a biomarker for blood glucose levels, suggesting that recording their activity <i>in vivo</i> could support patients suffering from diabetes mellitus with long-term automated read-out of blood glucose concentrations. Here, we present a flexible polymer-based implant having 64 low impedance microelectrodes designed to be implanted to a depth of 10 mm into the pancreas. As a first step, the implant will be used in acute experiments in pigs to explore the electrophysiological processes of the pancreas <i>in vivo</i>. Beyond use in the pancreas, our flexible implant and simple implantation method may also be used in other organs such as the brain.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00662-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10123442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kathrine Curtin, Jing Wang, Bethany J. Fike, Brandi Binkley, Peng Li
{"title":"A 3D printed microfluidic device for scalable multiplexed CRISPR-cas12a biosensing","authors":"Kathrine Curtin, Jing Wang, Bethany J. Fike, Brandi Binkley, Peng Li","doi":"10.1007/s10544-023-00675-x","DOIUrl":"10.1007/s10544-023-00675-x","url":null,"abstract":"<div><p>Accurate, rapid, and multiplexed nucleic acid detection is critical for environmental and biomedical monitoring. In recent years, CRISPR-Cas12a has shown great potential in improving the performance of DNA biosensing. However, the nonspecific <i>trans</i>-cleavage activity of Cas12a complicates the multiplexing capability of Cas12a biosensing. We report a 3D-printed composable microfluidic plate (cPlate) device that utilizes miniaturized wells and microfluidic loading for a multiplexed CRISPR-Cas12a assay. The device easily combines loop-mediated isothermal amplification (LAMP) and CRISPR-Cas12a readout in a simple and high-throughput workflow with low reagent consumption. To ensure the maximum performance of the device, the concentration of Cas12a and detection probe was optimized, which yielded a four-fold sensitivity improvement. Our device demonstrates sensitive detection to the fg mL<sup>− 1</sup> level for four waterborne pathogens including shigella, campylobacter, cholera, and legionella within 1 h, making it suitable for low-resource settings.</p><h3>Graphical Abstract</h3>\u0000 <div><figure><div><div><picture><source><img></source></picture></div></div></figure></div>\u0000 </div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10175383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Filipe Marques, Wouter van der Wijngaart, Niclas Roxhed
{"title":"Absorbable cyst brushes","authors":"Filipe Marques, Wouter van der Wijngaart, Niclas Roxhed","doi":"10.1007/s10544-023-00674-y","DOIUrl":"10.1007/s10544-023-00674-y","url":null,"abstract":"<div><p>Cytobrushes are used for low-invasive sample collection and screening in multiple diseases, with a significant impact on early detection, prevention, and diagnosis. This study focuses on improving the safety of cell brushing in hard-to-reach locations by exploring brush construction from absorbable materials. We investigated the efficacy of loop brushes made of absorbable suture wires of Chirlac, Chirasorb, Monocryl, PDS II, Vicryl Rapid, Glycolon, and Catgut during their operation in conjunction with fine-needle aspiration in an artificial cyst model. PDS II brushes demonstrated the highest efficiency, while Monocryl and Catgut also provided a significant brushing effect. Efficient brushes portrayed higher flexural rigidity than their counterparts, and their efficiency was inversely proportional to their plastic deformation by the needle. Our results open avenues for safer cell biopsies in hard-to-reach locations by utilizing brushes composed of absorbable materials.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10447279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10061831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chensong Xu, Gwenaël Bonfante, Jongho Park, Vincent Salles, Beomjoon Kim
{"title":"Fabrication of an electrospun polycaprolactone substrate for colorimetric bioassays","authors":"Chensong Xu, Gwenaël Bonfante, Jongho Park, Vincent Salles, Beomjoon Kim","doi":"10.1007/s10544-023-00673-z","DOIUrl":"10.1007/s10544-023-00673-z","url":null,"abstract":"<div><p>Colorimetric assays rely on detecting colour changes to measure the concentration of target molecules. Paper substrates are commonly used for the detection of biomarkers due to their availability, porous structure, and capillarity. However, the morphological and mechanical properties of paper, such as fibre diameter, pore size, and tensile strength, cannot be easily tuned to meet the specific requirements of colorimetric sensors, including liquid capacity and reagent immobilisation. As an alternative to paper materials, biodegradable polymeric membranes made of electrospun polycaprolactone (PCL) fibres can provide various tunable properties related to fibre diameter and pore size.</p><p>We aimed to obtain a glucose sensor substrate for colorimetric sensing using electrospinning with PCL. A feeding solution was created by mixing PCL/chloroform and 3,3’,5’,5’-tetramethylbenzidine (TMB)/ethanol solutions. This solution was electrospun to fabricate a porous membrane composed of microfibres consist of PCL and TMB. The central area of the membrane was made hydrophilic through air plasma treatment, and it was subsequently functionalized with a solution containing glucose oxidase, horseradish peroxidase, and trehalose.</p><p>The sensing areas were evaluated by measuring colour changes in glucose solutions of varying concentrations. The oxidation reactions of glucose and TMB in sensor substrates were recorded and analysed to establish the correlation between different glucose concentrations and colour changes. For comparison, conventional paper substrates prepared with same parameters were evaluated alongside the electrospun PCL substrates. As a result, better immobilization of reagents and higher sensitivity of glucose were achieved with PCL substrates, indicating their potential usage as a new sensing substrate for bioassays.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10435419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10057234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Suman Chatterjee, Rathin K. Joshi, Tushar Sakorikar, Bhagaban Behera, Nitu Bhaskar, Shabari Girishan KV, Mahesh Jayachandra, Hardik J. Pandya
{"title":"Design and fabrication of a microelectrode array for studying epileptiform discharges from rodents","authors":"Suman Chatterjee, Rathin K. Joshi, Tushar Sakorikar, Bhagaban Behera, Nitu Bhaskar, Shabari Girishan KV, Mahesh Jayachandra, Hardik J. Pandya","doi":"10.1007/s10544-023-00672-0","DOIUrl":"10.1007/s10544-023-00672-0","url":null,"abstract":"<div><p>Local field potentials, the extracellular electrical activities from brain regions, provide clinically relevant information about the status of neurophysiological conditions, including epilepsy. In this study, a 13-channel silicon-based single-shank microelectrode array (MEA) was designed and fabricated to record local field potentials (LFPs) from the different depths of a rat’s brain. A titanium/gold layer was patterned as electrodes on an oxidized silicon substrate, and silicon dioxide was deposited as a passivation layer. The fabricated array was implanted in the somatosensory cortex of the right hemisphere of an anesthetized rat. The developed MEA was interfaced with an OpenBCI Cyton Daisy Biosensing Board to acquire the local field potentials. The LFPs were acquired at three different neurophysiological conditions, including baseline signals, chemically-induced epileptiform discharges, and recovered baseline signals after anti-epileptic drug (AED) administration. Further, time-frequency analyses were performed on the acquired biopotentials to study the difference in spatiotemporal features. The processed signals and time-frequency analyses clearly distinguish between pre-convulsant and post-AED baselines and evoked epileptiform discharges.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10057230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A multi-depth spiral milli fluidic device for whole mount zebrafish antibody staining","authors":"Songtao Ye, Wei-Chun Chin, Chih-Wen Ni","doi":"10.1007/s10544-023-00670-2","DOIUrl":"10.1007/s10544-023-00670-2","url":null,"abstract":"<div><p>Whole mount zebrafish antibody staining (ABS) is a common staining technique used to localize protein information in a zebrafish embryo or larva. Like most biological assays, the whole mount zebrafish ABS is still largely conducted manually through labor intensive and time-consuming steps which affect both consistency and throughput of the assay. In this work, we develop a milli fluidic device that can automatically trap and immobilize the fixed chorion-less zebrafish embryos for the whole mount ABS. With just a single loading step, the zebrafish embryos can be trapped by the milli fluidic device through a chaotic hydrodynamic trapping process. Moreover, a consistent body orientation (i.e., head point inward) for the trapped zebrafish embryos can be achieved without additional orientation adjustment device. Furthermore, we employed a consumer-grade SLA 3D printer assisted method for device prototyping which is ideal for labs with limited budgets. Notably, the milli fluidic device has enabled the optimization and successful implementation of whole mount zebrafish Caspase-3 ABS. We demonstrated our device can accelerate the overall procedure by reducing at least 50% of washing time in the standard well-plate-based manual procedure. Also, the consistency is improved, and manual steps are reduced using the milli fluidic device. This work fills the gap in the milli fluidic application for whole mount zebrafish immunohistochemistry. We hope the device can be accepted by the zebrafish community and be used for other types of whole mount zebrafish ABS procedures or expanded to more complicated <i>in situ</i> hybridization (ISH) procedure.</p><h3>Graphical Abstract</h3>\u0000 <div><figure><div><div><picture><source><img></source></picture></div></div></figure></div>\u0000 </div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10427545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10113836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Valentina Di Francesco, Daniela P. Boso, Thomas L. Moore, Bernhard A. Schrefler, Paolo Decuzzi
{"title":"Machine learning instructed microfluidic synthesis of curcumin-loaded liposomes","authors":"Valentina Di Francesco, Daniela P. Boso, Thomas L. Moore, Bernhard A. Schrefler, Paolo Decuzzi","doi":"10.1007/s10544-023-00671-1","DOIUrl":"10.1007/s10544-023-00671-1","url":null,"abstract":"<div><p>The association of machine learning (ML) tools with the synthesis of nanoparticles has the potential to streamline the development of more efficient and effective nanomedicines. The continuous-flow synthesis of nanoparticles via microfluidics represents an ideal playground for ML tools, where multiple engineering parameters – flow rates and mixing configurations, type and concentrations of the reagents – contribute in a non-trivial fashion to determine the resultant morphological and pharmacological attributes of nanomedicines. Here we present the application of ML models towards the microfluidic-based synthesis of liposomes loaded with a model hydrophobic therapeutic agent, curcumin. After generating over 200 different liposome configurations by systematically modulating flow rates, lipid concentrations, organic:water mixing volume ratios, support-vector machine models and feed-forward artificial neural networks were trained to predict, respectively, the liposome dispersity/stability and size. This work presents an initial step towards the application and cultivation of ML models to instruct the microfluidic formulation of nanoparticles.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10404166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10412855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}