Marta K. Orlowska, James R. Krycer, Janice D. Reid, Richard J. Mills, Michael R. Doran, James E. Hudson
{"title":"A miniaturized culture platform for control of the metabolic environment","authors":"Marta K. Orlowska, James R. Krycer, Janice D. Reid, Richard J. Mills, Michael R. Doran, James E. Hudson","doi":"10.1063/5.0169143","DOIUrl":"https://doi.org/10.1063/5.0169143","url":null,"abstract":"The heart is a metabolic “omnivore” and adjusts its energy source depending on the circulating metabolites. Human cardiac organoids, a three-dimensional in vitro model of the heart wall, are a useful tool to study cardiac physiology and pathology. However, cardiac tissue naturally experiences shear stress and nutrient fluctuations via blood flow in vivo, whilst in vitro models are conventionally cultivated in a static medium. This necessitates the regular refreshing of culture media, which creates acute cellular disturbances and large metabolic fluxes. To culture human cardiac organoids in a more physiological manner, we have developed a perfused bioreactor for cultures in a 96-well plate format. The designed bioreactor is easy to fabricate using a common culture plate and a 3D printer. Its open system allows for the use of traditional molecular biology techniques, prevents flow blockage issues, and provides easy access for sampling and cell assays. We hypothesized that a perfused culture would create more stable environment improving cardiac function and maturation. We found that lactate is rapidly produced by human cardiac organoids, resulting in large fluctuations in this metabolite under static culture. Despite this, neither medium perfusion in bioreactor culture nor lactate supplementation improved cardiac function or maturation. In fact, RNA sequencing revealed little change across the transcriptome. This demonstrates that cardiac organoids are robust in response to fluctuating environmental conditions under normal physiological conditions. Together, we provide a framework for establishing an easily accessible perfusion system that can be adapted to a range of miniaturized cell culture systems.","PeriodicalId":8855,"journal":{"name":"Biomicrofluidics","volume":"4 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140018702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Niloy Barua, Ashlee M. Herken, Natalie Melendez-Velador, Thomas G. Platt, Ryan R. Hansen
{"title":"Photo-addressable microwell devices for rapid functional screening and isolation of pathogen inhibitors from bacterial strain libraries","authors":"Niloy Barua, Ashlee M. Herken, Natalie Melendez-Velador, Thomas G. Platt, Ryan R. Hansen","doi":"10.1063/5.0188270","DOIUrl":"https://doi.org/10.1063/5.0188270","url":null,"abstract":"Discovery of new strains of bacteria that inhibit pathogen growth can facilitate improvements in biocontrol and probiotic strategies. Traditional, plate-based co-culture approaches that probe microbial interactions can impede this discovery as these methods are inherently low-throughput, labor-intensive, and qualitative. We report a second-generation, photo-addressable microwell device, developed to iteratively screen interactions between candidate biocontrol agents existing in bacterial strain libraries and pathogens under increasing pathogen pressure. Microwells (0.6 pl volume) provide unique co-culture sites between library strains and pathogens at controlled cellular ratios. During sequential screening iterations, library strains are challenged against increasing numbers of pathogens to quantitatively identify microwells containing strains inhibiting the highest numbers of pathogens. Ring-patterned 365 nm light is then used to ablate a photodegradable hydrogel membrane and sequentially release inhibitory strains from the device for recovery. Pathogen inhibition with each recovered strain is validated, followed by whole genome sequencing. To demonstrate the rapid nature of this approach, the device was used to screen a 293-membered biovar 1 agrobacterial strain library for strains inhibitory to the plant pathogen Agrobacterium tumefaciens sp. 15955. One iterative screen revealed nine new inhibitory strains. For comparison, plate-based methods did not uncover any inhibitory strains from the library (n = 30 plates). The novel pathogen-challenge screening mode developed here enables rapid selection and recovery of strains that effectively suppress pathogen growth from bacterial strain libraries, expanding this microwell technology platform toward rapid, cost-effective, and scalable screening for probiotics, biocontrol agents, and inhibitory molecules that can protect against known or emerging pathogens.","PeriodicalId":8855,"journal":{"name":"Biomicrofluidics","volume":"79 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140004423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Harnessing the power of Microscale AcoustoFluidics: A perspective based on BAW cancer diagnostics","authors":"C. L. Harshbarger","doi":"10.1063/5.0180158","DOIUrl":"https://doi.org/10.1063/5.0180158","url":null,"abstract":"Cancer directly affects one in every three people, and mortality rates strongly correlate with the stage at which diagnosis occurs. Each of the multitude of methods used in cancer diagnostics has its own set of advantages and disadvantages. Two common drawbacks are a limited information value of image based diagnostic methods and high invasiveness when opting for methods that provide greater insight. Microfluidics offers a promising avenue for isolating circulating tumor cells from blood samples, offering high informational value at predetermined time intervals while being minimally invasive. Microscale AcoustoFluidics, an active method capable of manipulating objects within a fluid, has shown its potential use for the isolation and measurement of circulating tumor cells, but its full potential has yet to be harnessed. Extensive research has focused on isolating single cells, although the significance of clusters should not be overlooked and requires attention within the field. Moreover, there is room for improvement by designing smaller and automated devices to enhance user-friendliness and efficiency as illustrated by the use of bulk acoustic wave devices in cancer diagnostics. This next generation of setups and devices could minimize streaming forces and thereby enable the manipulation of smaller objects, thus aiding in the implementation of personalized oncology for the next generation of cancer treatments.","PeriodicalId":8855,"journal":{"name":"Biomicrofluidics","volume":"1 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140004456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomicrofluidicsPub Date : 2024-02-27eCollection Date: 2024-01-01DOI: 10.1063/5.0180394
Pinja Elomaa, Tuomas Ojalehto, Darshan Kumar, Ville Jokinen, Päivi Saavalainen
{"title":"Manually pressurized droplet digital PCR chip for rapid SARS-CoV-2 diagnostics.","authors":"Pinja Elomaa, Tuomas Ojalehto, Darshan Kumar, Ville Jokinen, Päivi Saavalainen","doi":"10.1063/5.0180394","DOIUrl":"10.1063/5.0180394","url":null,"abstract":"<p><p>Droplet digital PCR (ddPCR) is a technique in which PCR reaction is divided into thousands of nanoliter-sized droplets and has proven to be a great tool in virus diagnostics. Compared to the gold standard system quantitative real-time PCR (RT-qPCR), ddPCR functions particularly well when dealing with samples with low template counts, such as viral concentration. This feature makes the technique suitable for early detection of the virus. In this study, a novel portable PDMS ddPCR chip is introduced. The chip functions without external pumps using manual pressurization with a multichannel pipet. The created droplets are monodispersed and form a monolayer on the chip's collection chamber, from where they can be effortlessly imaged. Droplets were analyzed and counted using artificial intelligence. The use of the manually pressurized chip was demonstrated for a SARS-CoV-2 assay, which takes advantage of isothermal strand invasion-based amplification (SIBA) technology, allowing quick and accurate, even point-of-care analysis of the sample. The results demonstrate that SIBA assays can be divided into nanoliter-sized droplets and used as quantitative assays, giving an approximation of the samples' viral count.</p>","PeriodicalId":8855,"journal":{"name":"Biomicrofluidics","volume":"18 1","pages":"014106"},"PeriodicalIF":3.2,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10901548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Surface-dominant micro/nanofluidics for efficient green energy conversion","authors":"Cong Wang, Eunseok Seo, Jungyul Park","doi":"10.1063/5.0190934","DOIUrl":"https://doi.org/10.1063/5.0190934","url":null,"abstract":"Green energy conversion in aqueous systems has attracted considerable interest owing to the sustainable clean energy demand resulting from population and economic growth and urbanization, as well as the significant potential energy from water resources and other regenerative sources coupled with fluids. In particular, molecular motion based on intrinsic micro/nanofluidic phenomena at the liquid–solid interface (LSI) is crucial for efficient and sustainable green energy conversion. The electrical double layer is the main factor affecting transport, interaction between molecules and surfaces, non-uniform ion distribution, synthesis, stimulated reactions, and motion by external renewable resources in both closed nanoconfinement and open surfaces. In this review, we summarize the state-of-the-art progress in physical and chemical reaction-based green energy conversion in LSI, including nanoscale fabrication, key mechanisms, applications, and limitations for practical implementation. The prospects for resolving critical challenges in this field and inspiring other promising research areas in the infancy stage (studying chemical and biological dynamics at the single-molecule level and nanofluidic neuromorphic computing) are also discussed.","PeriodicalId":8855,"journal":{"name":"Biomicrofluidics","volume":"5 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139762771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tao Peng, Chenxiao Zhou, Zhexin Zhang, Yingying Liu, Xiaodong Lin, Yongqing Ye, Yunlong Zhong, Ping Wang, Yanwei Jia
{"title":"Review on bile dynamics and microfluidic-based component detection: Advancing the understanding of bilestone pathogenesis in the biliary tract","authors":"Tao Peng, Chenxiao Zhou, Zhexin Zhang, Yingying Liu, Xiaodong Lin, Yongqing Ye, Yunlong Zhong, Ping Wang, Yanwei Jia","doi":"10.1063/5.0186602","DOIUrl":"https://doi.org/10.1063/5.0186602","url":null,"abstract":"Bilestones are solid masses found in the gallbladder or biliary tract, which block the normal bile flow and eventually result in severe life-threatening complications. Studies have shown that bilestone formation may be related to bile flow dynamics and the concentration level of bile components. The bile flow dynamics in the biliary tract play a critical role in disclosing the mechanism of bile stasis and transportation. The concentration of bile composition is closely associated with processes such as nucleation and crystallization. Recently, microfluidic-based biosensors have been favored for multiple advantages over traditional benchtop detection assays for their less sample consumption, portability, low cost, and high sensitivity for real-time detection. Here, we reviewed the developments in bile dynamics study and microfluidics-based bile component detection methods. These studies may provide valuable insights into the bilestone formation mechanisms and better treatment, alongside our opinions on the future development of in vitro lithotriptic drug screening of bilestones and bile characterization tests.","PeriodicalId":8855,"journal":{"name":"Biomicrofluidics","volume":"20 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139762341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Microfluidic devices integrated with plasmonic nanostructures for sensitive fluorescent immunoassays.","authors":"Xuefeng Xu, Guangyang Li, Lingyue Xue, Shurong Dong, Jikui Luo, Zhen Cao","doi":"10.1063/5.0174653","DOIUrl":"10.1063/5.0174653","url":null,"abstract":"<p><p>The robust identification and quantification of various biomarkers is of utmost significance in clinical diagnostics and precision medicine. Fluorescent immunoassays are widely used and considered as a gold standard for biomarker detection due to their high specificity and accuracy. However, current commercial immunoassay tests suffer from limited detection sensitivity and complicated, labor-intensive operation procedures, making them impractical for point-of-care diagnosis, particularly in resource-limited regions. Recently, microfluidic immunoassay devices integrated with plasmonic nanostructures have emerged as a powerful tool for sensitive detection of biomarkers, addressing specific issues, such as integration schemes, easy operation, multiplexed detection, and sensitivity enhancement. In this paper, we provide a discussion on the recent advances in the plasmonic nanostructures integrated with microfluidic devices for fluorescent immunoassays. We shed light on the nanofabrication strategies and various fluidic designs for rapid, sensitive, and highly efficient sensing of antigens. Finally, we share our perspectives on the potential directions of these integrated devices for practical applications.</p>","PeriodicalId":8855,"journal":{"name":"Biomicrofluidics","volume":"18 1","pages":"011303"},"PeriodicalIF":3.2,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10869169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139740260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomicrofluidicsPub Date : 2024-02-07eCollection Date: 2024-01-01DOI: 10.1063/5.0189413
Yudong Wang, Niladri Talukder, Bharath Babu Nunna, Eon Soo Lee
{"title":"Dean vortex-enhanced blood plasma separation in self-driven spiral microchannel flow with cross-flow microfilters.","authors":"Yudong Wang, Niladri Talukder, Bharath Babu Nunna, Eon Soo Lee","doi":"10.1063/5.0189413","DOIUrl":"10.1063/5.0189413","url":null,"abstract":"<p><p>Point-of-care (POC) diagnostic devices have been developing rapidly in recent years, but they are mainly using saliva instead of blood as a test sample. A highly efficient self-separation during the self-driven flow without power systems is desired for expanding the point-of-care diagnostic devices. Microfiltration stands out as a promising technique for blood plasma separation but faces limitations due to blood cell clogging, resulting in reduced separation speed and efficiency. These limitations are mainly caused by the high viscosity and hematocrit in the blood flow. A small increment in the hematocrit of the blood significantly increases the pressure needed for the blood plasma separation in the micro-filters and decreases the separation speed and efficiency. Addressing this challenge, this study explores the feasibility of diluting whole blood within a microfluidic device without external power systems. This study implemented a spiral microchannel utilizing the inertial focusing and Dean vortex effects to focus the red blood cells and extract the blood with lower hematocrit. The inertial migration of the particles during the capillary flow was first investigated experimentally; a maximum of 88% of the particles migrated to the bottom and top equilibrium positions in the optimized 350 × 60 <i>μ</i>m (cross-sectional area, 5.8 aspect ratio) microchannel. With the optimized dimension of the microchannel, the whole blood samples within the physiological hematocrit range were tested in the experiments, and more than 10% of the hematocrit reduction was compared between the outer branch outlet and inner branch outlet in the 350 × 60 <i>μ</i>m microchannel.</p>","PeriodicalId":8855,"journal":{"name":"Biomicrofluidics","volume":"18 1","pages":"014104"},"PeriodicalIF":2.6,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10853010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vamsi Vikram Gande, Prem K. R. Podupu, Bianca Berry, Nandkishor K. Nere, S. Pushpavanam, Meenesh R. Singh
{"title":"Engineering advancements in microfluidic systems for enhanced mixing at low Reynolds numbers","authors":"Vamsi Vikram Gande, Prem K. R. Podupu, Bianca Berry, Nandkishor K. Nere, S. Pushpavanam, Meenesh R. Singh","doi":"10.1063/5.0178939","DOIUrl":"https://doi.org/10.1063/5.0178939","url":null,"abstract":"Mixing within micro- and millichannels is a pivotal element across various applications, ranging from chemical synthesis to biomedical diagnostics and environmental monitoring. The inherent low Reynolds number flow in these channels often results in a parabolic velocity profile, leading to a broad residence time distribution. Achieving efficient mixing at such small scales presents unique challenges and opportunities. This review encompasses various techniques and strategies to evaluate and enhance mixing efficiency in these confined environments. It explores the significance of mixing in micro- and millichannels, highlighting its relevance for enhanced reaction kinetics, homogeneity in mixed fluids, and analytical accuracy. We discuss various mixing methodologies that have been employed to get a narrower residence time distribution. The role of channel geometry, flow conditions, and mixing mechanisms in influencing the mixing performance are also discussed. Various emerging technologies and advancements in microfluidic devices and tools specifically designed to enhance mixing efficiency are highlighted. We emphasize the potential applications of micro- and millichannels in fields of nanoparticle synthesis, which can be utilized for biological applications. Additionally, the prospects of machine learning and artificial intelligence are offered toward incorporating better mixing to achieve precise control over nanoparticle synthesis, ultimately enhancing the potential for applications in these miniature fluidic systems.","PeriodicalId":8855,"journal":{"name":"Biomicrofluidics","volume":"10 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139590531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiomicrofluidicsPub Date : 2024-01-25eCollection Date: 2024-01-01DOI: 10.1063/5.0172550
Meenakshi Pinnenti, Muhammad Ahsan Sami, Umer Hassan
{"title":"Enabling biomedical technologies for chronic myelogenous leukemia (CML) biomarkers detection.","authors":"Meenakshi Pinnenti, Muhammad Ahsan Sami, Umer Hassan","doi":"10.1063/5.0172550","DOIUrl":"10.1063/5.0172550","url":null,"abstract":"<p><p>Chronic myelogenous/myeloid leukemia (CML) is a type of cancer of bone marrow that arises from hematopoietic stem cells and affects millions of people worldwide. Eighty-five percent of the CML cases are diagnosed during chronic phase, most of which are detected through routine tests. Leukocytes, micro-Ribonucleic Acids, and myeloid markers are the primary biomarkers for CML diagnosis and are mainly detected using real-time reverse transcription polymerase chain reaction, flow cytometry, and genetic testing. Though multiple therapies have been developed to treat CML, early detection still plays a pivotal role in the overall patient survival rate. The current technologies used for CML diagnosis are costly and are confined to laboratory settings which impede their application in the point-of-care settings for early-stage detection of CML. This study provides detailed analysis and insights into the significance of CML, patient symptoms, biomarkers used for testing, and best possible detection techniques responsible for the enhancement in survival rates. A critical and detailed review is provided around potential microfluidic devices that can be adapted to detect the biomarkers associated with CML while enabling point-of-care testing for early diagnosis of CML to improve patient survival rates.</p>","PeriodicalId":8855,"journal":{"name":"Biomicrofluidics","volume":"18 1","pages":"011501"},"PeriodicalIF":2.6,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10817778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139569875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}