{"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":"On-chip construction of a fully structured scaffold-free vascularized renal tubule","authors":"Yuntian Zhu, Zhengdi Shi, Weiping Ding, Chengpan Li","doi":"10.1007/s10544-023-00648-0","DOIUrl":"10.1007/s10544-023-00648-0","url":null,"abstract":"<div><p>Renal tubule chips have emerged as a promising platform for drug nephrotoxicity testing. However, the reported renal tubule chips hardly replicate the unique structure of renal tubules with thick proximal and distal tubules and a thin loop of Henle. In this study, we developed a fully structured scaffold-free vascularized renal tubule on a microfluidic chip. On the chip, the renal epithelial cell-laden hollow calcium-polymerized alginate tube with thick segments at both ends and a thin middle segment was U-shaped embedded in collagen hydrogel, parallel to the endothelial cell-laden hollow calcium-polymerized alginate tube with uniform tube diameter. After the alginate tubes were on-chip degraded, the renal epithelial cells and endothelial cells automatically attached to the collagen hydrogel and proliferated to form the renal tubule with proximal tubule, loop of Henle and distal tubule as well as peritubular blood vessel. We evaluated the viability of cells on the hollow alginate tubes, characterized the distribution and morphology of cells before and after the degradation of the alginate tube, and confirmed the proliferation of cells and the metabolic function of cells in terms of ATP synthesis, fibronectin secretion and VEGFR2 expression on the chip. The enhanced metabolic functions of renal epithelial cells and endothelial cells were preliminarily demonstrated. This study provides new insights into designing a more biomimetic renal tubule on a microfluidic chip.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00648-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5267012","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}
Yang Xu, Sundeep Mangla, Paul Gschneidner, Yong Shi
{"title":"A multi-asperity adhesive contact model for catheter and vascular artery contact in endovascular surgery","authors":"Yang Xu, Sundeep Mangla, Paul Gschneidner, Yong Shi","doi":"10.1007/s10544-023-00646-2","DOIUrl":"10.1007/s10544-023-00646-2","url":null,"abstract":"<div><h2>Abstract\u0000</h2><div><p>Contact behaviors of medical devices, such as guidewires and catheters, are critical in endovascular surgeries. In this work, a new method to predict adhesive contact force between catheter and vascular artery is presented. Multi-asperity adhesion on the surface of vascular artery, deformation of asperity and deformation of vascular substrate are all considered. The single asperity behavior is described with Johnson-Kendall-Roberts (JKR) contact model. The multi-asperity behavior is based on Greenwood–Williamson (GW) asperity model. Vascular substrate is considered as elastic bulk substrate and its deformation is determined with Hertzian pressure from asperity on a circular region on the elastic half space. The model shows that the deformation of vascular substrate accounts for the majority of the total contact deformation and significantly affects the predicted contact force. The model is verified with published experimental data. The comparison shows that the model produces very accurate prediction of contact force between catheter and vascular artery when the contact force is compressive. Parametric analysis based on asperity topography is carried out. The analysis shows that the diameter of the circular region of the interface between asperity and vascular substrate has more significant effect on the estimation of contact force than the radius of asperity. Further validation of prediction accuracy of the model under experiment is needed.</p></div></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00646-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5176530","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}
Panpan Qiao, Luo Yu, Hongying Liu, Xueping Yan, Xitian Pi
{"title":"An intelligent intestinal bleeding diagnosis and treatment capsule system based on color recognition","authors":"Panpan Qiao, Luo Yu, Hongying Liu, Xueping Yan, Xitian Pi","doi":"10.1007/s10544-022-00642-y","DOIUrl":"10.1007/s10544-022-00642-y","url":null,"abstract":"<div><p>To our best knowledge, there are no non-invasive and painless means for the diagnosis and treatment of intestinal bleeding as of now, especially the segment of intestine that cannot be reached by endoscopy. We proposed an intelligent intestinal bleeding diagnosis and treatment capsule (IBDTC) system for the first time to diagnose and treat intestinal bleeding with low power consumption, estimated to be about 2.16mW. A hue-saturation-light (HSL) color space method was applied to diagnose bleeding according to H (hue) values of the film dyed by blood. A MEMS-based micro-igniter works as the critical component of the micro-thruster that houses the propellant (74.6% potassium nitrate, 11.9% sulfur, 13.5% charcoal) and the detonating agent (dinitrodiazophenol), to help release drug. Bleeding detection and ignition tests were performed to justify its feasibility and reliability. Results demonstrated that the bleeding diagnosis module of the IBDTC can effectively detect bleeding and the micro-igniter can successfully ignite the propellant. Owing to its simplicity and intelligence, the IBDTC system will pave a way for future accurate treatment of small intestinal bleeding with no injury, no pain, no complicated supporting equipment, no need for <i>in vitro</i> operation and positioning.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-022-00642-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4967987","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":"Piezoelectric micropump with integrated elastomeric check valves: design, performance characterization and primary application for 3D cell culture","authors":"Joseph Benjamin Holman, Xiaolu Zhu, Hao Cheng","doi":"10.1007/s10544-022-00645-9","DOIUrl":"10.1007/s10544-022-00645-9","url":null,"abstract":"<div><p>This paper reports on the study of a piezoelectric actuated micropump with integrated elastomeric check valves that can transport small amounts of fluid in a highly controllable manner. The proposed micropump consists of a piezoelectric actuated fluid chamber with two integrated elastomeric check valves for regulating input and output flow direction, while restricting backflows. The actuation, fluid dynamic response and fluid–structure interactions at various working cycles are studied through a fully coupled multiphysics simulation (solid mechanics, electrostatic and fluid flow). The pump bodies are manufactured by micromachining of PMMA sheets, while the middle elastomeric membrane and diaphragm are fabricated by spin-coating PDMS. The experimental results confirm that the micropump can provide sufficiently low-velocity outflow for biomedical applications between 3.4 – 41.8 µl/min. The performance of the micropump is improved significantly through a convenient geometric modification of an off-the-shelf piezoelectric brass disc. Furthermore, the combination of this micropump with the 3D cell-culture microfluidic chip realizes the dynamic culture of cells encapsulated in 3D hydrogels with a continuous flowing medium, which offers the potential for changing the traditional mode of 3D cell culture with a static supply of nutrition and factors.</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 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4682596","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}
Timothy R. Olsen, Claudia Tapia-Alveal, Kechun Wen, Tilla S. Worgall, Milan N. Stojanovic, Qiao Lin
{"title":"Microfluidic isolation of aptamers with affinity towards multiple myeloma monoclonal immunoglobulins","authors":"Timothy R. Olsen, Claudia Tapia-Alveal, Kechun Wen, Tilla S. Worgall, Milan N. Stojanovic, Qiao Lin","doi":"10.1007/s10544-022-00643-x","DOIUrl":"10.1007/s10544-022-00643-x","url":null,"abstract":"<div><p>Multiple myeloma (MM) is a bone marrow cancer of resident plasma cells that affects 125,000 patients in the U.S. with about 30,000 new cases per year. Its signature is the clonal proliferation of a single plasma cell that secretes a patient specific monoclonal immunoglobulin (M-Ig). Targeting the M-Ig in patient serum could allow sensitive and noninvasive identification of minimal residual disease in multiple myeloma. Aptamers, which are single-stranded oligonucleotides with affinity and specificity to a target molecule, have recently been introduced as affinity reagents for recognition of MM M-Igs. Here we exploit microfluidic SELEX technology to enable rapid and efficient generation of aptamers against M-Ig proteins from MM patients. We first characterize the technology by isolating aptamers with affinity towards the monoclonal antibody rituximab as a model M-Ig and then apply the technology to isolating aptamers specifically targeting M-Igs obtained from serum samples of MM patients. We demonstrate that high-affinity DNA aptamers (K<sub>D</sub> < 50 nM) for M-Ig proteins from a patient sample could be isolated via microfluidic SELEX within approximately 12 h and using less than 100 micrograms of patient M-Ig. Such aptamers can potentially be used in personalized monitoring of minimal residual disease in MM patients.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2022-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4331216","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}
Shadi Emam, Mehdi Nasrollahpour, John Patrick Allen, Yifan He, Hussein Hussein, Harsh Shailesh Shah, Fariborz Tavangarian, Nian-Xiang Sun
{"title":"A handheld electronic device with the potential to detect lung cancer biomarkers from exhaled breath","authors":"Shadi Emam, Mehdi Nasrollahpour, John Patrick Allen, Yifan He, Hussein Hussein, Harsh Shailesh Shah, Fariborz Tavangarian, Nian-Xiang Sun","doi":"10.1007/s10544-022-00638-8","DOIUrl":"10.1007/s10544-022-00638-8","url":null,"abstract":"<div><p>Lung cancer is the leading cause of cancer death in the United States. It has the lowest 5-year survival rate among the most common cancers and therefore, early diagnosis is critical to improve the survival rate. In this paper, a new handheld electronic device is proposed to detect nine lung cancer biomarkers in the exhaled breath. An electrochemical gas sensor was produced through deposition of a thin layer of graphene and Prussian blue on a chromium-modified silicon substrate. Selective binding of the analyte was formed by molecular imprinting polymer (MIP). Subsequent polymerization and removal of the analyte yielded a layer of a conductive polymer on top of the sensor containing molecularly imprinted cavities selective for the target molecule. The sensors were tested over 1–20 parts per trillion (ppt) level of concentration while the sensor resistance has been monitored as the sensors react to the analyte by resistance change. Pentane sensor was also tested for selectivity. A printed circuit board was designed to measure the resistance of each sensor and send the data to a developed application in smartphone through Bluetooth. This handheld device has the potential to be used as a diagnostic method in the near future.</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":"24 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2022-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4735056","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}
Fariba Malekpour Galogahi, Abolfazl Ansari, Adrian J. T. Teo, Haotian Cha, Hongjie An, Nam-Trung Nguyen
{"title":"Fabrication and characterization of core–shell microparticles containing an aqueous core","authors":"Fariba Malekpour Galogahi, Abolfazl Ansari, Adrian J. T. Teo, Haotian Cha, Hongjie An, Nam-Trung Nguyen","doi":"10.1007/s10544-022-00637-9","DOIUrl":"10.1007/s10544-022-00637-9","url":null,"abstract":"<div><p>Core–shell microparticles containing an aqueous core have demonstrated their value for microencapsulation and drug delivery systems. The most important step in generating these uniquely structured microparticles is the formation of droplets and double emulsion. The droplet generator must meet the performance and reliability requirements, including accurate size control with tunability and monodispersity. Herein, we present a facile technique to generate surfactant-free core–shell droplets with an aqueous core in a microfluidic device. We demonstrate that the geometry of the core–shell droplets can be precisely adjusted by the flow rates of the droplet components. As the shell is polymerized after the formation of the core–shell droplets, the resulting solid microparticles ensure the encapsulation of the aqueous core and prevent undesired release. We then study experimentally and theoretically the behaviour of resultant microparticles under heating and compression. The microparticles demonstrate excellent stability under both thermal and mechanical loads. We show that the rupture force can be quantitatively predicted from the shell thickness relative to the outer shell radius. Experimental results and theoretical predictions confirm that the rupture force scales directly with the shell thickness.</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":"24 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2022-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-022-00637-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4433927","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}
Abdulwadood Al-Ali, Ahmed Elwakil, Brent Maundy, Sohaib Majzoub
{"title":"Fast Sub-Hz potentiostatic/galvanostatic bio-impedance measurements using chaotic oscillators","authors":"Abdulwadood Al-Ali, Ahmed Elwakil, Brent Maundy, Sohaib Majzoub","doi":"10.1007/s10544-022-00641-z","DOIUrl":"10.1007/s10544-022-00641-z","url":null,"abstract":"<div><p>The measurement of bio-impedance spectra at ultra low frequencies (sub-Hz) is known to require a considerably long time with the classical frequency-sweep method or other narrow-band periodic excitation signals. In this work, an impedance measurement technique based on using wide-band chaotic signals is proposed and experimentally validated over the frequency range <span>(10,mHz-1,Hz)</span>. The technique was tested in both potentiostatic and galvanostatic modes, first using commercial components and then using an enhanced Howland current pump designed and fabricated in a 65nm CMOS technology. The accuracy of the proposed technique was assessed on fruit samples compared to measurements conducted using a research-grade Biologic VSP-300 electro-chemical station.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"24 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2022-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4402986","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}