Biomedical Microdevices最新文献

{"title":"A multiplexed microfluidic continuous-flow electroporation system for efficient cell transfection","authors":"Jacob A. VanderBurgh,&nbsp;Grant T. Corso,&nbsp;Stephen L. Levy,&nbsp;Harold G. Craighead","doi":"10.1007/s10544-023-00692-w","DOIUrl":"10.1007/s10544-023-00692-w","url":null,"abstract":"<div><p>Cellular therapies have the potential to advance treatment for a broad array of diseases but rely on viruses for genetic reprogramming. The time and cost required to produce viruses has created a bottleneck that constricts development of and access to cellular therapies. Electroporation is a non-viral alternative for genetic reprogramming that bypasses these bottlenecks, but current electroporation technology suffers from low throughput, tedious optimization, and difficulty scaling to large-scale cell manufacturing. Here, we present an adaptable microfluidic electroporation platform with the capability for rapid, multiplexed optimization with 96-well plates. Once parameters are optimized using small volumes of cells, transfection can be seamlessly scaled to high-volume cell manufacturing without re-optimization. We demonstrate optimizing transfection of plasmid DNA to Jurkat cells, screening hundreds of different electrical waveforms of varying shapes at a speed of ~3 s per waveform using ~20 µL of cells per waveform. We selected an optimal set of transfection parameters using a low-volume flow cell. These parameters were then used in a separate high-volume flow cell where we obtained similar transfection performance by design. This demonstrates an alternative non-viral and economical transfection method for scaling to the volume required for producing a cell therapy without sacrificing performance. Importantly, this transfection method is disease-agnostic with broad applications beyond cell therapy.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139401286","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":"Fabrication of lidocaine-loaded polymer dissolving microneedles for rapid and prolonged local anesthesia","authors":"Yanan Mao,&nbsp;Xiufeng Zhang,&nbsp;Yanfang Sun,&nbsp;Zhong Shen,&nbsp;Chao Zhong,&nbsp;Lei Nie,&nbsp;Amin Shavandi,&nbsp;Khaydar E. Yunusov,&nbsp;Guohua Jiang","doi":"10.1007/s10544-024-00695-1","DOIUrl":"10.1007/s10544-024-00695-1","url":null,"abstract":"<div><p>There is an urgent need for research into effective interventions for pain management to improve patients’ life quality. Traditional needle and syringe injection were used to administer the local anesthesia. However, it causes various discomforts, ranging from brief stings to trypanophobia and denial of medical operations. In this study, a dissolving microneedles (MNs) system made of composite matrix materials of polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), and sodium hyaluronate (HA) was successfully developed for the loading of lidocaine hydrochloride (LidH). The morphology, size and mechanical properties of the MNs were also investigated. After the insertion of MNs into the skin, the matrix at the tip of the MNs was swelled and dissolved by absorption of interstitial fluid, leading to a rapid release of loaded LidH from MNs’ tips. And the LidH in the back patching was diffused into deeper skin tissue through microchannels created by MNs insertion, forming a prolonged anesthesia effect. In addition, the back patching of MNs could be acted as a drug reservoir to form a prolonged local anesthesia effect. The results showed that LidH MNs provided a superior analgesia up to 8 h, exhibiting a rapid and long-lasting analgesic effects. Additionally, tissue sectioning and in vitro cytotoxicity tests indicated that the MNs patch we developed had a favorable biosafety profile.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139376958","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 disposable impedimetric immunosensor for the analysis of CA125 in human serum samples","authors":"Merve Yılmaz,&nbsp;Melike Bilgi","doi":"10.1007/s10544-023-00691-x","DOIUrl":"10.1007/s10544-023-00691-x","url":null,"abstract":"<div><p>Cancer antigen 125 (CA125) is the most common biomarker used to diagnose and monitor ovarian cancer progression for the last four decades, and precise detection of its levels in blood serum is crucial. In this work, label-free impedimetric CA125 immunosensors were fabricated by using screen-printed carbon electrodes modified with poly toluidine blue (PTB) (in deep eutectic solvent)/gold nanoparticles (AuNP) for the sensitive, environmentally friendly, economical, and practical analysis of CA125. The materials of PTB_DES and AuNP were characterized by Fourier Transform Infrared (FT-IR), Scanning Electron Microscope (FE-SEM), and X-ray Diffraction (XRD). The analysis of the CA125 was performed by electrochemical impedance spectroscopy and the developed immunosensor. The immunosensor's repeatability, reproducibility, reusability, selectivity, and storage stability were examined. The developed label-free immunosensor allowed the determination of CA125 in fast, good repeatability and a low limit of detection (1.20 pg mL⁻¹) in the linear range of 5–100 pg mL⁻¹. The stable surface of the fabricated immunosensor was successfully regenerated ten times. The application of immunosensors in commercial human blood serum was performed, and good recoveries were achieved. The disposable label-free impedimetric CA125 immunosensor developed for the rapid and practical detection of CA125 is a candidate for use in point-of-care tests in clinical applications of ovarian cancer.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139096983","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":"The effect of magnetic bead size on the isolation efficiency of lung cancer cells in a serpentine microchannel with added cavities","authors":"Tzu-Cheng Su,&nbsp;Hien Vu-Dinh,&nbsp;Shu-Hui Lin,&nbsp;Loc Do Quang,&nbsp;Trinh Chu Duc,&nbsp;Chun-Ping Jen","doi":"10.1007/s10544-023-00689-5","DOIUrl":"10.1007/s10544-023-00689-5","url":null,"abstract":"<div><p>An investigation was conducted to examine the effect of magnetic bead (MB) size on the effectiveness of isolating lung cancer cells using the immunomagnetic separation (IMS) method in a serpentine microchannel with added cavities (SMAC) structure. Carboxylated magnetic beads were specifically conjugated to target cells through a modification procedure using aptamer materials. Cells immobilized with different sizes (in micrometers) of MBs were captured and isolated in the proposed device for comparison and analysis. The study yields significance regarding the clarification of device working principles by using a computational model. Furthermore, an accurate evaluation of the MB size impact on capture efficiency was achieved, including the issue of MB-cell accumulation at the inlet-channel interface, despite it being overlooked in many previous studies. As a result, our findings demonstrated an increasing trend in binding efficiency as the MB size decreased, evidenced by coverages of 50.5%, 60.1%, and 73.4% for sizes of 1.36 μm, 3.00 μm, and 4.50 μm, respectively. Additionally, the overall capture efficiency (without considering the inlet accumulation) was also higher for smaller MBs. However, when accounting for the actual number of cells entering the channel (i.e., the effective capture), larger MBs showed higher capture efficiency. The highest effective capture achieved was 88.4% for the size of 4.50 μm. This research provides an extensive insight into the impact of MB size on the performance of IMS-based devices and holds promise for the efficient separation of circulating cancer cells (CTCs) in practical applications.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139085298","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":"Rapid-release reversible bonding of PMMA-based microfluidic devices with PBMA coating","authors":"Yusheng Li,&nbsp;Fan Xu,&nbsp;Jing liu,&nbsp;Qi Zhang,&nbsp;Yiqiang Fan","doi":"10.1007/s10544-023-00690-y","DOIUrl":"10.1007/s10544-023-00690-y","url":null,"abstract":"<div><p>PMMA-based microfluidics have been widely used in various applications in biological and chemical fields. In the fabrication process of PMMA-based microfluidics, the substrate and cover plate usually need to be bonded to enclose the microchannel. The bonding process could be permanent or reversible. In some application scenarios, reversible bonding is needed to retrieve the samples inside the channel or reuse the chip. Current reversible bonding methods for PMMA-based microfluidics usually have drawbacks on bonding strength and contaminations from the adhesives used in the bonding process. In this study, a new approach is proposed for the reversible bonding of PMMA-based microfluidics, a layer of PBMA (with a very similar structure to PMMA) was coated on the surface of PMMA and then use the thermal fusion method to achieve the bonding with a high bonding strength, a tensile bonding strength of around 0.8 MPa was achieved. For debond process, a rapid temperature drop will trigger the immediate release of the bonding within several seconds. Detailed bonding strength measurement and biocompatibility tests were also conducted in this study. The proposed bonding method could have wide application potential in the fabrication of PMMA-based microfluidics.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138883822","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":"Classification of fetal and adult red blood cells based on hydrodynamic deformation and deep video recognition","authors":"Peter Johannes Tejlgaard Kampen,&nbsp;Gustav Ragnar Støttrup-Als,&nbsp;Nicklas Bruun-Andersen,&nbsp;Joachim Secher,&nbsp;Freja Høier,&nbsp;Anne Todsen Hansen,&nbsp;Morten Hanefeld Dziegiel,&nbsp;Anders Nymark Christensen,&nbsp;Kirstine Berg-Sørensen","doi":"10.1007/s10544-023-00688-6","DOIUrl":"10.1007/s10544-023-00688-6","url":null,"abstract":"<div><p>Flow based deformation cytometry has shown potential for cell classification. We demonstrate the principle with an injection moulded microfluidic chip from which we capture videos of adult and fetal red blood cells, as they are being deformed in a microfluidic chip. Using a deep neural network - SlowFast - that takes the temporal behavior into account, we are able to discriminate between the cells with high accuracy. The accuracy was larger for adult blood cells than for fetal blood cells. However, no significant difference was observed between donors of the two types.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00688-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138631195","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":"Performance gain and electro-mechanical design optimization of microneedles for wearable sensor systems","authors":"Marco Fratus,&nbsp;Muhammad Ashraful Alam","doi":"10.1007/s10544-023-00683-x","DOIUrl":"10.1007/s10544-023-00683-x","url":null,"abstract":"<p>Minimally invasive microneedle (MN) is an emerging technology platform for wearable and implantable diagnostics and therapeutics systems. These short MNs offer pain-free insertion and simple operation. Among the MN technologies proposed to enhance interstitial fluid (ISF) extraction, porous and swellable (P-S) hydrogels absorb analyte molecules across the entire lateral surface. Currently, the design, development, and optimization of the MNs rely on empirical, iterative approaches. Based on theory of fluid flow and analyte diffusion through geometrically complex biomimetic systems, here we derive a generalized physics-guided model for P-S MN sensors. The framework (a) quantifies MN extracting efficiency <span>({eta _textrm{PS}})</span> in terms of its geometric and physical properties, and (b) suggests strategies to optimize sensor response while satisfying the mechanical constraints related to various skin-types (e.g., mouse, pig, humans, etc.). Our results show that, despite the differences in geometry and composition, P-S MNs obey a universal scaling response, <span>({eta }_textrm{PS} sim zeta left( frac{textrm{h}_textrm{T} textrm{l}_textrm{n}^textrm{2}}{textrm{D}_textrm{n}textrm{s}} right) ^textrm{n})</span> with <span>(textrm{l}_textrm{n}, textrm{D}_textrm{n}, textrm{s})</span> being MN length, diffusivity, and radius, respectively, and <span>({zeta })</span>, <span>(textrm{h}_textrm{T})</span> and <span>(textrm{n})</span> are the ratio between approximate vs. exact analytical solutions, the effective biofluid transfer coefficient between dermis and skin, and the exponent for the power-law approximation, respectively. These parameters quantify the biomolecule transfer through the dermis-to-MN interface at different scaling limits. P-S MNs outperform hollow MNs by a 2-6x enhancement factor; however, the buckling-limit of insertion defines the maximized functionality of the sensor. Our model, validated against experimental results and numerical simulations, offers a predictive design framework to significantly reduce the optimization time for P-S MN-based sensor platforms.</p>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138631355","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":"Label-free microfluidic chip for segregation and recovery of circulating leukemia cells: clinical applications in acute myeloid leukemia","authors":"Dongfang Ouyang,&nbsp;Ningxin Ye,&nbsp;Yue Jiang,&nbsp;Yiyang Wang,&nbsp;Lina Hu,&nbsp;Shuen Chao,&nbsp;Martin Yarmush,&nbsp;Memet Tuner,&nbsp;Yonghua Li,&nbsp;Bin Tang","doi":"10.1007/s10544-023-00687-7","DOIUrl":"10.1007/s10544-023-00687-7","url":null,"abstract":"<div><p>We present a label-free microfluidic chip for the segregation of circulating leukemia cells (CLCs) from blood samples, with a focus on its clinical applications in Acute Myeloid Leukemia (AML). The microfluidic chip achieved an approximate capture efficiency of 92%. The study analyzed a comprehensive set of 66 blood specimens from AML patients in different disease stages, including newly diagnosed and relapsing cases, patients in complete remission, and those in partial remission. The results showed a significant difference in CLC counts between active disease stages and remission stages (p &lt; 0.0001), with a proposed threshold of 5 CLCs to differentiate between the two. The microfluidic chip exhibited a sensitivity of 95.4% and specificity of 100% in predicting disease recurrence. Additionally, the captured CLCs were subjected to downstream molecular analysis using droplet digital PCR, allowing for the identification of genetic mutations associated with AML. Comparative analysis with bone marrow aspirate processing by FACS demonstrated the reliability and accuracy of the microfluidic chip in tracking disease burden, with highly agreement results obtained between the two methods. The non-invasive nature of the microfluidic chip and its ability to provide real-time insights into disease progression make it a promising tool for the proactive monitoring and personalized patient care of AML.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138570812","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":"Embedded macrophages induce intravascular coagulation in 3D blood vessel-on-chip","authors":"H.H.T. Middelkamp,&nbsp;H.J. Weener,&nbsp;T. Gensheimer,&nbsp;K. Vermeul,&nbsp;L.E. de Heus,&nbsp;H.J. Albers,&nbsp;A. van den Berg,&nbsp;A.D. van der Meer","doi":"10.1007/s10544-023-00684-w","DOIUrl":"10.1007/s10544-023-00684-w","url":null,"abstract":"<div><p>Macrophages are innate immune cells that prevent infections and help in wound healing and vascular inflammation. While these cells are natural helper cells, they also contribute to chronic diseases, e.g., by infiltrating the endothelial layer in early atherosclerosis and by promoting vascular inflammation. There is a crosstalk between inflammatory pathways and key players in thrombosis, such as platelets and endothelial cells – a phenomenon known as ‘thromboinflammation’. The role of the embedded macrophages in thromboinflammation in the context of vascular disease is incompletely understood. Blood vessels-on-chips, which are microfluidic vascular cell culture models, have been used extensively to study aspects of vascular disease, like permeability, immune cell adhesion and thrombosis. Blood perfusion assays in blood vessel-on-chip models benefit from multiple unique aspects of the models, such as control of microvessel structure and well-defined flow patterns, as well as the ability to perform live imaging. However, due to their simplified nature, blood vessels-on-chip models have not yet been used to capture the complex cellular crosstalk that is important in thromboinflammation. Using induced pluripotent stem cell-derived endothelial cells and polarized THP-1 monocytes, we have developed and systematically set up a 3D blood vessel-on-chip with embedded (lipid-laden) macrophages, which is created using sequential cell seeding in viscous finger patterned collagen hydrogels. We have set up a human whole blood perfusion assay for these 3D blood vessels-on-chip. An increased deposition of fibrin in the blood vessel-on-chip models containing lipid-laden macrophages was observed. We anticipate the future use of this advanced vascular <i>in vitro</i> model in drug development for early atherosclerosis or aspects of other vascular diseases.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-023-00684-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138570824","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":"An in silico model of the capturing of magnetic nanoparticles in tumour spheroids in the presence of flow","authors":"Barbara Wirthl,&nbsp;Christina Janko,&nbsp;Stefan Lyer,&nbsp;Bernhard A. Schrefler,&nbsp;Christoph Alexiou,&nbsp;Wolfgang A. Wall","doi":"10.1007/s10544-023-00685-9","DOIUrl":"10.1007/s10544-023-00685-9","url":null,"abstract":"<p>One of the main challenges in improving the efficacy of conventional chemotherapeutic drugs is that they do not reach the cancer cells at sufficiently high doses while at the same time affecting healthy tissue and causing significant side effects and suffering in cancer patients. To overcome this deficiency, magnetic nanoparticles as transporter systems have emerged as a promising approach to achieve more specific tumour targeting. Drug-loaded magnetic nanoparticles can be directed to the target tissue by applying an external magnetic field. However, the magnetic forces exerted on the nanoparticles fall off rapidly with distance, making the tumour targeting challenging, even more so in the presence of flowing blood or interstitial fluid. We therefore present a computational model of the capturing of magnetic nanoparticles in a test setup: our model includes the flow around the tumour, the magnetic forces that guide the nanoparticles, and the transport within the tumour. We show how a model for the transport of magnetic nanoparticles in an external magnetic field can be integrated with a multiphase tumour model based on the theory of porous media. Our approach based on the underlying physical mechanisms can provide crucial insights into mechanisms that cannot be studied conclusively in experimental research alone. Such a computational model enables an efficient and systematic exploration of the nanoparticle design space, first in a controlled test setup and then in more complex <i>in vivo</i> scenarios. As an effective tool for minimising costly trial-and-error design methods, it expedites translation into clinical practice to improve therapeutic outcomes and limit adverse effects for cancer patients.</p>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10678808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440118","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}