Melike Bilgi Kamaç, Muhammed Altun, Merve Yılmaz, Ayla Yılmaz Aktan, Soner Aktan, Mustafa Kemal Sezgintürk
{"title":"Point-of-care testing: a disposable label-free electrochemical CA125 and HE4 immunosensors for early detection of ovarian cancer","authors":"Melike Bilgi Kamaç, Muhammed Altun, Merve Yılmaz, Ayla Yılmaz Aktan, Soner Aktan, Mustafa Kemal Sezgintürk","doi":"10.1007/s10544-023-00659-x","DOIUrl":"10.1007/s10544-023-00659-x","url":null,"abstract":"<div><p>Cancer antigen 125 (CA125) and human epididymal secretory protein 4 (HE4) are critical biomarkers for ovarian cancer diagnosis and progression monitoring; therefore, sensitive determination of their levels in body fluids is crucial. In recent study, label-free CA125 and HE4 immunosensors were prepared using disposable screen-printed carbon electrodes modified with reduced graphene oxide, polythionine, and gold nanoparticles for the sensitive, fast, and practical determination of CA125 and HE4. Differential pulse voltammetry, square wave voltammetry, and electrochemical impedance spectroscopy methods were used for the electrochemical determination of antigens in four different linear ranges (1-100 pg mL<sup>− 1</sup>, 0.01-10 ng mL<sup>− 1</sup>, 10–50 ng mL<sup>− 1,</sup> and 50–500 ng mL<sup>− 1</sup>). High sensitivity, low limit of detection, and limit of quantification were obtained for each linear range with a correlation coefficient above 0.99. The application stability of CA125 and HE4 immunosensors was determined as 60 days, and the storage stability was determined as 16 weeks. Immunosensors showed high selectivity in nine different antigen mixtures. The reusability of the immunosensors has been tested up to 9 cycles. The Risk of Ovarian Malignancy Algorithm score% values were calculated using the concentration of CA125 and HE4 in the blood serum and evaluated in terms of ovarian cancer risk. For the point-of-care testing, CA125 and HE4 levels at pg mL<sup>− 1</sup> concentration were measured in blood serum samples using the developed immunosensors and a hand-held electrochemical reader in approximately 20–30 s, and high recoveries were obtained. These disposable label-free immunosensors are user-friendly and can be used in point-of-care tests for rapid and practical detection of CA125 and HE4 with high selectivity, sensitivity, and repeatability.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00659-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4178360","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}
{"title":"Paper-based multiplex biosensors for inexpensive healthcare diagnostics: a comprehensive review","authors":"Shrishti Kumari, Monsur Islam, Ankur Gupta","doi":"10.1007/s10544-023-00656-0","DOIUrl":"10.1007/s10544-023-00656-0","url":null,"abstract":"<div><p>Multiplex detection is a smart and an emerging approach in point-of-care testing as it reduces analysis time and testing cost by detecting multiple analytes or biomarkers simultaneously which are crucial for disease detection at an early stage. Application of inexpensive substrate such as paper has immense potential and matter of research interest in the area of point of care testing for multiplexed analysis as it possesses several unique advantages. This study presents the use of paper, strategies adopted to refine the design created on paper and lateral flow strips to enhance the signal, increase the sensitivity and specificity of multiplexed biosensors. An overview of different multiplexed detection studies performed using biological samples has also been reviewed along with the challenges and advantages offered by multiplexed analysis.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00656-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4137791","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}
Matthew A A Smith, M Ibrahim Khot, Silvia Taccola, Nicholas R Fry, Pirkko L Muhonen, Joanne L Tipper, David G Jayne, Robert W Kay, Russell A Harris
{"title":"A digitally driven manufacturing process for high resolution patterning of cell formations","authors":"Matthew A A Smith, M Ibrahim Khot, Silvia Taccola, Nicholas R Fry, Pirkko L Muhonen, Joanne L Tipper, David G Jayne, Robert W Kay, Russell A Harris","doi":"10.1007/s10544-023-00655-1","DOIUrl":"10.1007/s10544-023-00655-1","url":null,"abstract":"<div><p>This paper presents the engineering and validation of an enabling technology that facilitates new capabilities in <i>in vitro</i> cell models for high-throughput screening and tissue engineering applications. This is conducted through a computerized system that allows the design and deposition of high-fidelity microscale patterned coatings that selectively alter the chemical and topographical properties of cell culturing surfaces. Significantly, compared to alternative methods for microscale surface patterning, this is a digitally controlled and automated process thereby allowing scientists to rapidly create and explore an almost infinite range of cell culture patterns. This new capability is experimentally validated across six different cell lines demonstrating how the precise microscale deposition of these patterned coatings can influence spatiotemporal growth and movement of endothelial, fibroblast, neuronal and macrophage cells. To further demonstrate this platform, more complex patterns are then created and shown to guide the behavioral response of colorectal carcinoma cells.</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 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00655-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4812586","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}
Kuiguo Han, Bin Jiang, Yanqun Tong, Wen Zhang, Xiaobo Zou, Jiyong Shi, Xiaoyu Su
{"title":"Flexible-fabricated sensor module with programmable magnetic actuators coupled to L-cysteine functionalized Ag@Fe3O4 complexes for Cu2+ detection in fish tissues","authors":"Kuiguo Han, Bin Jiang, Yanqun Tong, Wen Zhang, Xiaobo Zou, Jiyong Shi, Xiaoyu Su","doi":"10.1007/s10544-023-00654-2","DOIUrl":"10.1007/s10544-023-00654-2","url":null,"abstract":"<div><h2>Abstract\u0000</h2><div><p>Heavy metal contamination for seafood, particularly fish, is arising great concerns, and consequentially it is necessary to develop a simple and direct detection method. In this work, Ag@Fe<sub>3</sub>O<sub>4</sub> is successfully prepared by simple solvothermal method, and we present a flexible-fabricated sensor module with assembled programmable magnetic actuators. The resulting sensor integrates a three-electrode system with two programmable magnetic actuators at the bottom of the device, which regulates the amount of current by adjusting the brake to control the adsorption force and vibration. The L-Cysteine functionalized Ag@Fe<sub>3</sub>O<sub>4</sub> is coated on the surface of the electrode, then the Cu<sup>2+</sup> is dropped into the reaction tank. Its performance is studied by cyclic voltammetry and electrochemical impedance spectroscopy, and the key experimental conditions such as deposition potential, deposition time, and electrolyte pH are gradually optimized. Under optimal conditions, Cu<sup>2+</sup> can be detected over a wide linear range (0.01 ~ 4 μM) and at a low LOD (0.34 nM). The results show that the proposed method has a good application prospect in the detection of Cu<sup>2+</sup>. This method is successfully applied to Cu<sup>2+</sup> analysis in fish samples with an acceptable recovery of 93 ~ 102%.</p></div></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4406032","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}
James Comolli, David I. Walsh III, Johanna Bobrow, Chelsea L. Lennartz, Nicholas J. Guido, Todd Thorsen
{"title":"An in vitro platform for study of the human gut microbiome under an oxygen gradient","authors":"James Comolli, David I. Walsh III, Johanna Bobrow, Chelsea L. Lennartz, Nicholas J. Guido, Todd Thorsen","doi":"10.1007/s10544-023-00653-3","DOIUrl":"10.1007/s10544-023-00653-3","url":null,"abstract":"<div><p>The complex, dynamic environment of the human lower gastrointestinal tract is colonized by hundreds of bacterial species that impact health and performance. Ex vivo study of the functional interactions between microbial community members in conditions representative of those in the gut is an ongoing challenge. We have developed an <i>in vitro</i> 40-plex platform that provides an oxygen gradient to support simultaneous maintenance of microaerobic and anaerobic microbes from the gut microbiome that can aid in rapid characterization of microbial interactions and direct comparison of individual microbiome samples. In this report, we demonstrate that the platform more closely maintained the microbial diversity and composition of human donor fecal microbiome samples than strict anaerobic conditions. The oxygen gradient established in the platform allowed the stratification and subsequent sampling of diverse microbial subpopulations that colonize microaerobic and anaerobic micro-environments. With the ability to run forty samples in parallel, the platform has the potential to be used as a rapid screening tool to understand how the gut microbiome responds to environmental perturbations such as toxic compound exposure, dietary changes, or pharmaceutical treatments.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00653-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4149111","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}
{"title":"A two-minute assay for electronic quantification of antibodies in saliva enabled through a reusable microfluidic multi-frequency impedance cytometer and machine learning analysis","authors":"Zhongtian Lin, Jianye Sui, Mehdi Javanmard","doi":"10.1007/s10544-023-00647-1","DOIUrl":"10.1007/s10544-023-00647-1","url":null,"abstract":"<div><p>The use of saliva as a diagnostic fluid has always been appealing due to the ability for rapid and non-invasive sampling for monitoring health status and the onset and progression of disease and treatment progress. Saliva is rich in protein biomarkers and provides a wealth of information for diagnosis and prognosis of various disease conditions. Portable electronic tools which rapidly monitor protein biomarkers would facilitate point-of-care diagnosis and monitoring of various health conditions. For example, the detection of antibodies in saliva can enable rapid diagnosis and tracking disease pathogenesis of various auto-immune diseases like sepsis. Here, we present a novel method involving immuno-capture of proteins on antibody coated beads and electrical detection of dielectric properties of the beads. The changes in electrical properties of a bead when capturing proteins are extremely complex and difficult to model physically in an accurate manner. The ability to measure impedance of thousands of beads at multiple frequencies, however, allows for a data-driven approach for protein quantification. By moving from a physics driven approach to a data driven approach, we have developed, for the first time ever to the best of our knowledge, an electronic assay using a reusable microfluidic impedance cytometer chip in conjunction with supervised machine learning to quantifying immunoglobulins G (IgG) and immunoglobulins A (IgA) in saliva within two minutes.\u0000</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00647-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4727920","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}
Kaixin sun, Ben Whiteside, Michael Hebda, Yiqiang Fan, Yajun Zhang, Yumeng Xie, KunMing Liang
{"title":"A low-cost and hand-hold PCR microdevice based on water-cooling technology","authors":"Kaixin sun, Ben Whiteside, Michael Hebda, Yiqiang Fan, Yajun Zhang, Yumeng Xie, KunMing Liang","doi":"10.1007/s10544-023-00652-4","DOIUrl":"10.1007/s10544-023-00652-4","url":null,"abstract":"<div><p>Polymerase chain reaction (PCR) has become a powerful tool for detecting various diseases due to its high sensitivity and specificity. However, the long thermocycling time and the bulky system have limited the application of PCR devices in Point-of-care testing. Herein, we have proposed an efficient, low-cost, and hand-hold PCR microdevice, mainly including a control module based on water-cooling technology and an amplification module fabricated by 3D printing. The whole device is tiny and can be easily hand-held with a size of about 110 mm × 100 mm × 40 mm and a weight of about 300 g at a low cost of about $170.83. Based on the water-cooling technology, the device can efficiently perform 30 thermal cycles within 46 min at a heating/cooling rate of 4.0/8.1 ℃/s. To test our instrument, plasmid DNA dilutions were amplified with this device; the results demonstrate successful nucleic acid amplification of the plasmid DNA and exhibit the promise of this device for Point-of-care testing.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00652-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4727921","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}
{"title":"Cellular microarrays for assessing single-cell phenotypic changes in vascular cell populations","authors":"E. Smith, M. Zagnoni, M. E. Sandison","doi":"10.1007/s10544-023-00651-5","DOIUrl":"10.1007/s10544-023-00651-5","url":null,"abstract":"<div><p>Microengineering technologies provide bespoke tools for single-cell studies, including microarray approaches. There are many challenges when culturing adherent single cells in confined geometries for extended periods, including the ability of migratory cells to overcome confining cell-repellent surfaces with time. Following studies suggesting clonal expansion of only a few vascular smooth muscle cells (vSMCs) contributes to plaque formation, the investigation of vSMCs at the single-cell level is central to furthering our understanding of atherosclerosis. Herein, we present a medium throughput cellular microarray, for the tracking of single, freshly-isolated vSMCs as they undergo phenotypic modulation <i>in vitro</i>. Our solution facilitates long-term cell confinement (> 3 weeks) utilising novel application of surface functionalisation methods to define individual culture microwells. We demonstrate successful tracking of hundreds of native vSMCs isolated from rat aortic and carotid artery tissue, monitoring their proliferative capacity and uptake of oxidised low-density lipoprotein (oxLDL) by live-cell microscopy. After 7 days <i>in vitro</i>, the majority of viable SMCs remained as single non-proliferating cells (51% aorta, 78% carotid). However, a sub-population of vSMCs demonstrated high proliferative capacity (≥ 10 progeny; 18% aorta, 5% carotid), in line with reports that a limited number of medial SMCs selectively expand to populate atherosclerotic lesions. Furthermore, we show that, when exposed to oxLDL, proliferative cells uptake higher levels of lipoproteins, whilst also expressing greater levels of galectin-3. Our microwell array approach enables long-term characterisation of multiple phenotypic characteristics and the identification of new cellular sub-populations in migratory, proliferative adherent cell types.</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 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00651-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4656891","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}
E. Alperay Tarim, Muge Anil Inevi, Ilayda Ozkan, Seren Kecili, Eyup Bilgi, M. Semih Baslar, Engin Ozcivici, Ceyda Oksel Karakus, H. Cumhur Tekin
{"title":"Microfluidic-based technologies for diagnosis, prevention, and treatment of COVID-19: recent advances and future directions","authors":"E. Alperay Tarim, Muge Anil Inevi, Ilayda Ozkan, Seren Kecili, Eyup Bilgi, M. Semih Baslar, Engin Ozcivici, Ceyda Oksel Karakus, H. Cumhur Tekin","doi":"10.1007/s10544-023-00649-z","DOIUrl":"10.1007/s10544-023-00649-z","url":null,"abstract":"<div><p>The COVID-19 pandemic has posed significant challenges to existing healthcare systems around the world. The urgent need for the development of diagnostic and therapeutic strategies for COVID-19 has boomed the demand for new technologies that can improve current healthcare approaches, moving towards more advanced, digitalized, personalized, and patient-oriented systems. Microfluidic-based technologies involve the miniaturization of large-scale devices and laboratory-based procedures, enabling complex chemical and biological operations that are conventionally performed at the macro-scale to be carried out on the microscale or less. The advantages microfluidic systems offer such as rapid, low-cost, accurate, and on-site solutions make these tools extremely useful and effective in the fight against COVID-19. In particular, microfluidic-assisted systems are of great interest in different COVID-19-related domains, varying from direct and indirect detection of COVID-19 infections to drug and vaccine discovery and their targeted delivery. Here, we review recent advances in the use of microfluidic platforms to diagnose, treat or prevent COVID-19. We start by summarizing recent microfluidic-based diagnostic solutions applicable to COVID-19. We then highlight the key roles microfluidics play in developing COVID-19 vaccines and testing how vaccine candidates perform, with a focus on RNA-delivery technologies and nano-carriers. Next, microfluidic-based efforts devoted to assessing the efficacy of potential COVID-19 drugs, either repurposed or new, and their targeted delivery to infected sites are summarized. We conclude by providing future perspectives and research directions that are critical to effectively prevent or respond to future pandemics.</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 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00649-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4838856","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}
Yuntian Zhu, Zhengdi Shi, Weiping Ding, Chengpan Li
{"title":"Correction to: On-chip construction of a fully structured scaffold-free vascularized renal tubule","authors":"Yuntian Zhu, Zhengdi Shi, Weiping Ding, Chengpan Li","doi":"10.1007/s10544-023-00650-6","DOIUrl":"10.1007/s10544-023-00650-6","url":null,"abstract":"","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 2","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4471987","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}