Ahmed Hamza, Anagha Navale, Qingchuan Song, Sagar Bhagwat, Frederik Kotz-Helmer, Pegah Pezeshkpour, Bastian E. Rapp
{"title":"3D printed microfluidic valve on PCB for flow control applications using liquid metal","authors":"Ahmed Hamza, Anagha Navale, Qingchuan Song, Sagar Bhagwat, Frederik Kotz-Helmer, Pegah Pezeshkpour, Bastian E. Rapp","doi":"10.1007/s10544-024-00697-z","DOIUrl":"10.1007/s10544-024-00697-z","url":null,"abstract":"<div><p>Direct 3D printing of active microfluidic elements on PCB substrates enables high-speed fabrication of stand-alone microdevices for a variety of health and energy applications. Microvalves are key components of microfluidic devices and liquid metal (LM) microvalves exhibit promising flow control in microsystems integrated with PCBs. In this paper, we demonstrate LM microvalves directly 3D printed on PCB using advanced digital light processing (DLP). Electrodes on PCB are coated by carbon ink to prevent alloying between gallium-based LM plug and copper electrodes. We used DLP 3D printers with in-house developed acrylic-based resins, Isobornyl Acrylate, and Diurethane Dimethacrylate (DUDMA) and functionalized PCB surface with acrylic-based resin for strong bonding. Valving seats are printed in a 3D caterpillar geometry with chamber diameter of 700 µm. We successfully printed channels and nozzles down to 90 µm. Aiming for microvalves for low-power applications, we applied square-wave voltage of 2 V<sub>pp</sub> at a range of frequencies between 5 to 35 Hz. The results show precise control of the bistable valving mechanism based on electrochemical actuation of LMs.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10827904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139574377","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}
Youngeun Kim, Mary Beth Lewis, Jihyun Hwang, Zheyu Wang, Rohit Gupta, Yuxiong Liu, Tuhina Gupta, James P. Barber, Srikanth Singamaneni, Fred Quinn, Mark R. Prausnitz
{"title":"Microneedle patch-based enzyme-linked immunosorbent assay to quantify protein biomarkers of tuberculosis","authors":"Youngeun Kim, Mary Beth Lewis, Jihyun Hwang, Zheyu Wang, Rohit Gupta, Yuxiong Liu, Tuhina Gupta, James P. Barber, Srikanth Singamaneni, Fred Quinn, Mark R. Prausnitz","doi":"10.1007/s10544-024-00694-2","DOIUrl":"10.1007/s10544-024-00694-2","url":null,"abstract":"<div><p>There is a clinical need for differential diagnosis of the latent versus active stages of tuberculosis (TB) disease by a simple-to-administer test. Alpha-crystallin (Acr) and early secretory antigenic target-6 (ESAT-6) are protein biomarkers associated with the latent and active stages of TB, respectively, and could be used for differential diagnosis. We therefore developed a microneedle patch (MNP) designed for application to the skin to quantify Acr and ESAT-6 in dermal interstitial fluid by enzyme-linked immunosorbent assay (ELISA). We fabricated mechanically strong microneedles made of polystyrene and coated them with capture antibodies against Acr and ESAT-6. We then optimized assay sensitivity to achieve a limit of detection of 750 pg/ml and 3,020 pg/ml for Acr and ESAT-6, respectively. This study demonstrates the feasibility of an MNP-based ELISA for differential diagnosis of latent TB disease.</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":3.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139574382","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":"Magnetic nanoparticles fabricated/integrated with microfluidics for biological applications: A review","authors":"Mahtab Ghasemi Toudeshkchouei, Hassan Abdoos","doi":"10.1007/s10544-023-00693-9","DOIUrl":"10.1007/s10544-023-00693-9","url":null,"abstract":"<div><p>Nanostructured materials have gained significant attention in recent years for their potential in biological applications, such as cell and biomolecular sorting, as well as early detection of metastatic cancer. Among these materials, magnetic nanoparticles (MNPs) stand out for their easy functionalization, high specific surface area, chemical stability, and superparamagnetic properties. However, conventional fabrication methods can lead to inconsistencies in MNPs' characteristics and performance, highlighting the need for a cost-effective, controllable, and reproducible synthesis approach. In this review, we will discuss the utilization of microfluidic technology as a cutting-edge strategy for the continuous and regulated synthesis of MNPs. This approach has proven effective in producing MNPs with a superior biomedical performance by offering precise control over particle size, shape, and surface properties. We will examine the latest research findings on developing and integrating MNPs synthesized through continuous microfluidic processes for a wide range of biological applications. By providing an overview of the current state of the field, this review aims to showcase the advantages of microfluidics in the fabrication and integration of MNPs, emphasizing their potential to revolutionize diagnostic and therapeutic methods within the realm of biotechnology.</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":3.0,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545178","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":"Metal-based nanoparticles in antibacterial application in biomedical field: Current development and potential mechanisms","authors":"Hao Jiang, Lingzhi Li, Zhong Li, Xiang Chu","doi":"10.1007/s10544-023-00686-8","DOIUrl":"10.1007/s10544-023-00686-8","url":null,"abstract":"<div><p>The rise in drug resistance in pathogenic bacteria greatly endangers public health in the post-antibiotic era, and drug-resistant bacteria currently pose a great challenge not only to the community but also to clinical procedures, including surgery, stent implantation, organ transplantation, and other medical procedures involving any open wound and compromised human immunity. Biofilm-associated drug failure, as well as rapid resistance to last-resort antibiotics, necessitates the search for novel treatments against bacterial infection. In recent years, the flourishing development of nanotechnology has provided new insights for exploiting promising alternative therapeutics for drug-resistant bacteria. Metallic agents have been applied in antibacterial usage for several centuries, and the functional modification of metal-based biomaterials using nanotechnology has now attracted great interest in the antibacterial field, not only for their intrinsic antibacterial nature but also for their ready on-demand functionalization and enhanced interaction with bacteria, rendering them with good potential in further translation. However, the possible toxicity of MNPs to the host cells and tissue still hinders its application, and current knowledge on their interaction with cellular pathways is not enough. This review will focus on recent advances in developing metallic nanoparticles (MNPs), including silver, gold, copper, and other metallic nanoparticles, for antibacterial applications, and their potential mechanisms of interaction with pathogenic bacteria as well as hosts.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"26 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10806003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139519510","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}
Mohamed Adel, Ahmed Allam, Ashraf E. Sayour, Hani F. Ragai, Shinjiro Umezu, Ahmed M. R. Fath El-Bab
{"title":"Design and development of a portable low-cost QCM-based system for liquid biosensing","authors":"Mohamed Adel, Ahmed Allam, Ashraf E. Sayour, Hani F. Ragai, Shinjiro Umezu, Ahmed M. R. Fath El-Bab","doi":"10.1007/s10544-024-00696-0","DOIUrl":"10.1007/s10544-024-00696-0","url":null,"abstract":"<div><p>Quartz crystal microbalance (QCM) is a versatile sensing platform that has gained increasing attention for its use in bioapplications due to its high sensitivity, real-time measurement capabilities, and label-free detection. This article presents a portable QCM system for liquid biosensing that uses a modified Hartley oscillator to drive 14 mm-diameter commercial QCM sensors. The system is designed to be low-cost, easy to use, and highly sensitive, making it ideal for various bioapplications. A new flow cell design to deliver samples to the surface of the sensor has been designed, fabricated, and tested. For portability and miniaturization purposes, a micropump-based pumping system is used in the current system. The system has a built-in temperature controller allowing for accurate frequency measurements. In addition, the system can be used in benchtop mode. The capability of the present system to be used in liquid biosensing is demonstrated through an experimental test for sensitivity to changes in the viscosity of glycerol samples. It was found to have a sensitivity of 263.51 Hz/mPa.s using a 10 MHz QCM sensor. Future work regarding potential applications was suggested.</p><h3>Graphical Abstract</h3><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":3.0,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10796497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139484372","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}
Jacob A. VanderBurgh, Grant T. Corso, Stephen L. Levy, Harold G. Craighead
{"title":"A multiplexed microfluidic continuous-flow electroporation system for efficient cell transfection","authors":"Jacob A. VanderBurgh, Grant T. Corso, Stephen L. Levy, 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}
Yanan Mao, Xiufeng Zhang, Yanfang Sun, Zhong Shen, Chao Zhong, Lei Nie, Amin Shavandi, Khaydar E. Yunusov, Guohua Jiang
{"title":"Fabrication of lidocaine-loaded polymer dissolving microneedles for rapid and prolonged local anesthesia","authors":"Yanan Mao, Xiufeng Zhang, Yanfang Sun, Zhong Shen, Chao Zhong, Lei Nie, Amin Shavandi, Khaydar E. Yunusov, 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, 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<sub>DES</sub> 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<sup>−1</sup>) in the linear range of 5–100 pg mL<sup>−1</sup>. 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}
Tzu-Cheng Su, Hien Vu-Dinh, Shu-Hui Lin, Loc Do Quang, Trinh Chu Duc, Chun-Ping Jen
{"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, Hien Vu-Dinh, Shu-Hui Lin, Loc Do Quang, Trinh Chu Duc, 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}
Yusheng Li, Fan Xu, Jing liu, Qi Zhang, Yiqiang Fan
{"title":"Rapid-release reversible bonding of PMMA-based microfluidic devices with PBMA coating","authors":"Yusheng Li, Fan Xu, Jing liu, Qi Zhang, 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}