IU Indianapolis ScholarWorks :: Browsing by Subject "Microfluidics"

Browsing by Subject "Microfluidics"

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Acoustofluidic Assembly of 3D Neurospheroids to Model Alzheimer’s Disease
(Royal Society of Chemistry, 2020-09-28) Cai, Hongwei; Ao, Zheng; Hu, Liya; Moon, Younghye; Wu, Zhuhao; Lu, Hui-Chen; Kim, Jungsu; Guo, Feng; Medical and Molecular Genetics, School of Medicine
Neuroinflammation plays a central role in the progression of many neurodegenerative diseases such as Alzheimer's disease, and challenges remain in modeling the complex pathological or physiological processes. Here, we report an acoustofluidic method that can rapidly construct 3D neurospheroids and inflammatory microenvironments for modeling microglia-mediated neuroinflammation in Alzheimer's disease. By incorporating a unique contactless and label-free acoustic assembly, this cell culture platform can assemble dissociated embryonic mouse brain cells into hundreds of uniform 3D neurospheroids with controlled cell numbers, composition (e.g. neurons, astrocytes, and microglia), and environmental components (e.g. amyloid-β aggregates) in hydrogel within minutes. Moreover, this platform can maintain and monitor the interaction among neurons, astrocytes, microglia, and amyloid-β aggregates in real-time for several days to weeks, after the integration of a high-throughput, time-lapse cell imaging approach. We demonstrated that our engineered 3D neurospheroids can represent the amyloid-β neurotoxicity, which is one of the main pathological features of Alzheimer's disease. Using this method, we also investigated the microglia migratory behaviors and activation in the engineered 3D inflammatory microenvironment at a high throughput manner, which is not easy to achieve in 2D neuronal cultures or animal models. Along with the simple fabrication and setup, the acoustofluidic technology is compatible with conventional Petri dishes and well-plates, supports the fine-tuning of the cellular and environmental components of 3D neurospheroids, and enables the high-throughput cellular interaction investigation. We believe our technology may be widely used to facilitate 3D in vitro brain models for modeling neurodegenerative diseases, discovering new drugs, and testing neurotoxicity.
Acoustofluidic assembly of primary tumor-derived organotypic cell clusters for rapid evaluation of cancer immunotherapy
(BMC, 2023-02-04) Wu, Zhuhao; Ao, Zheng; Cai, Hongwei; Li, Xiang; Chen, Bin; Tu, Honglei; Wang, Yijie; Lu, Rongze Olivia; Gu, Mingxia; Cheng, Liang; Lu, Xin; Guo, Feng; Medicine, School of Medicine
Cancer immunotherapy shows promising potential for treating breast cancer. While patients may have heterogeneous treatment responses for adjuvant therapy, it is challenging to predict an individual patient’s response to cancer immunotherapy. Here, we report primary tumor-derived organotypic cell clusters (POCCs) for rapid and reliable evaluation of cancer immunotherapy. By using a label-free, contactless, and highly biocompatible acoustofluidic method, hundreds of cell clusters could be assembled from patient primary breast tumor dissociation within 2 min. Through the incorporation of time-lapse living cell imaging, the POCCs could faithfully recapitulate the cancer-immune interaction dynamics as well as their response to checkpoint inhibitors. Superior to current tumor organoids that usually take more than two weeks to develop, the POCCs can be established and used for evaluation of cancer immunotherapy within 12 h. The POCCs can preserve the cell components from the primary tumor due to the short culture time. Moreover, the POCCs can be assembled with uniform fabricate size and cell composition and served as an open platform for manipulating cell composition and ratio under controlled treatment conditions with a short turnaround time. Thus, we provide a new method to identify potentially immunogenic breast tumors and test immunotherapy, promoting personalized cancer therapy.
Integrated micro PEM fuel cell with self-regulated hydrogen generation from ammonia borane
(2015-08) Zamani Farahani, Mahmoud Reza; Zhu, Likun
An integrated micro PEM fuel cell system with self-regulated hydrogen generation from ammonia borane is reported to power portable electronics. Hydrogen is generated via catalytic hydrolysis reaction of ammonia borane solution in microchannels with nanoporous platinum catalyst electroplated inside the microchannels. The self-regulation of the ammonia borane solution is achieved by using directional growth and selective venting of hydrogen bubbles in microchannels, which leads to agitation and addition of fresh solution without power consumption. The device is fabricated on combination of polystyrene sheets cut by graphic cutter, a stainless steel layer cut using wire electrical discharge machining and bonding layers with double-sided polyimide tape. Due to the seamless bonding between the hydrogen generator and the micro fuel cell, the dead volume in the gas connection loops can be significantly reduced and the response time of self-regulation is reduced.
Integrated sensing and delivery of oxygen for next-generation smart wound dressings
(Springer Nature, 2020-05-18) Ochoa, Manuel; Rahimi, Rahim; Zhou, Jiawei; Jiang, Hongjie; Yoon, Chang Keun; Maddipatla, Dinesh; Narakathu, Binu Baby; Jain, Vaibhav; Oscai, Mark Michael; Morken, Thaddeus Joseph; Oliveira, Rebeca Hannah; Campana, Gonzalo L.; Cummings, Oscar W.; Zieger, Michael A.; Sood, Rajiv; Atashbar, Massood Z.; Ziaie, Babak; Pathology and Laboratory Medicine, School of Medicine
Chronic wounds affect over 6.5 million Americans and are notoriously difficult to treat. Suboptimal oxygenation of the wound bed is one of the most critical and treatable wound management factors, but existing oxygenation systems do not enable concurrent measurement and delivery of oxygen in a convenient wearable platform. Thus, we developed a low-cost alternative for continuous O2 delivery and sensing comprising of an inexpensive, paper-based, biocompatible, flexible platform for locally generating and measuring oxygen in a wound region. The platform takes advantage of recent developments in the fabrication of flexible microsystems including the incorporation of paper as a substrate and the use of a scalable manufacturing technology, inkjet printing. Here, we demonstrate the functionality of the oxygenation patch, capable of increasing oxygen concentration in a gel substrate by 13% (5 ppm) in 1 h. The platform is able to sense oxygen in a range of 5–26 ppm. In vivo studies demonstrate the biocompatibility of the patch and its ability to double or triple the oxygen level in the wound bed to clinically relevant levels.
Low power steering electrodes within microfluidic channels for blood cancer cell separation for MRD applications
(2015-12) Suryadevara, Vinay Kumar; Rizkalla, Maher; Farag, Sherif S.; Salama, Paul
In this study, a novel model for manipulating cancer blood cells based on multi-stage micro channels under varied low field concepts is proposed. Steering Device approach was followed to manipulate the cancer cells based on their various differential potentials across their membranes. The proposed approach considers the size and the surface potential as well as the iso electronic structure of the cells. These research objectives emphasize the separation of the cells in the blood stream, and differentiates various blood cells and tumors for further analysis within the microfluidic channels. The dimensions of the channel sets the required electric field for manipulating the cancer cells within the channels using low electrode voltage function. The outcomes of this research may introduce a new diagnostic approach of finding the minimum residual disease (MRD) scans, early detection and analysis scans. This thesis provides a mathematical model, detailing the theory of the cell sorting device, manipulating the blood cancer cells and design of the device structure are also detailed, leading to the optimum research parameters and process. A Computer Aided Design (CAD) was used to model the multi-cell sorting lab-on-chip device, details of hardware and software were used in the simulation of the device various stages. Reverse engineering to configure the potentials for sorting mechanism needs is discussed. The thesis work also presents a comparative study of this sorting mechanism and the other commercially available devices. The practical model of the proposed research is laid out for future consideration.
Microfluidics guided by deep learning for cancer immunotherapy screening
(National Academy of Science, 2022) Ao, Zheng; Cai, Hongwei; Wu, Zhuhao; Hu, Liya; Nunez, Asael; Zhou, Zhuolong; Liu, Hongcheng; Bondesson, Maria; Lu, Xiongbin; Lu, Xin; Dao, Ming; Guo, Feng; Medical and Molecular Genetics, School of Medicine
Immune-cell infiltration and cytotoxicity to pathogens and diseased cells are ubiquitous in health and disease. To better understand immune-cell behavior in a 3D environment, we developed an automated high-throughput microfluidic platform that enables real-time imaging of immune-cell infiltration dynamics and killing of the target cancer cells. We trained a deep learning algorithm using clinical data and integrated the algorithm with our microfluidic platform to effectively identify epigenetic drugs that promote T cell tumor infiltration and enhance cancer immunotherapy efficacy both in vitro and in vivo. Our platform provides a unique method to investigate immune-tissue interactions, which can be widely applied to oncology, immunology, neurology, microbiology, tissue engineering, regenerative medicine, translational medicine, and so on.
Modeling and design optimization of a microfluidic chip for isolation of rare cells
(2013-12) Gannavaram, Spandana; Zhu, Likun; Yu, Huidan (Whitney); Xie, Jian; Anwar, Sohel
Cancer is still among those diseases that prominently contribute to the numerous deaths that are caused each year. But as technology and research is reaching new zeniths in the present times, cure or early detection of cancer is possible. The detection of rare cells can help understand the origin of many diseases. The current study deals with one such technology that is used for the capture or effective separation of these rare cells called Lab-on-a-chip microchip technology. The isolation and capture of rare cells is a problem uniquely suited to microfluidic devices, in which geometries on the cellular length scale can be engineered and a wide range of chemical functionalizations can be implemented. The performance of such devices is primarily affected by the chemical interaction between the cell and the capture surface and the mechanics of cell-surface collision and adhesion. This study focuses on the fundamental adhesion and transport mechanisms in rare cell-capture microdevices, and explores modern device design strategies in a transport context. The biorheology and engineering parameters of cell adhesion are defined; chip geometries are reviewed. Transport at the microscale, cell-wall interactions that result in cell motion across streamlines, is discussed. We have concentrated majorly on the fluid dynamics design of the chip. A simplified description of the device would be to say that the chip is at micro scale. There are posts arranged on the chip such that the arrangement will lead to a higher capture of rare cells. Blood consisting of rare cells will be passed through the chip and the posts will pose as an obstruction so that the interception and capture efficiency of the rare cells increases. The captured cells can be observed by fluorescence microscopy. As compared to previous studies of using solid microposts, we will be incorporating a new concept of cylindrical shell micropost. This type of micropost consists of a solid inner core and the annulus area is covered with a forest of silicon nanopillars. Utilization of such a design helps in increasing the interception and capture efficiency and reducing the hydrodynamic resistance between the cells and the posts. Computational analysis is done for different designs of the posts. Drag on the microposts due to fluid flow has a great significance on the capture efficiency of the chip. Also, the arrangement of the posts is important to contributing to the increase in the interception efficiency. The effects of these parameters on the efficiency in junction with other factors have been studied and quantified. The study is concluded by discussing design strategies with a focus on leveraging the underlying transport phenomena to maximize device performance.
Recapitulation of complex transport and action of drugs at tumor microenvironment using tumor-microenvironment-on-chip
(Elsevier, 2016-09-28) Han, Bumsoo; Qu, Chunjing; Park, Kinam; Konieczny, Stephen F.; Korc, Murray; Medicine, School of Medicine
Targeted delivery aims to selectively distribute drugs to targeted tumor tissue but not to healthy tissue. This can address many of clinical challenges by maximizing the efficacy but minimizing the toxicity of anti-cancer drugs. However, complex tumor microenvironment poses various barriers hindering the transport of drugs and drug delivery systems. New tumor models that allow for the systematic study of these complex environments are highly desired to provide reliable test beds to develop drug delivery systems for targeted delivery. Recently, research efforts have yielded new in vitro tumor models, the so called tumor-microenvironment-on-chip, that recapitulate certain characteristics of the tumor microenvironment. These new models show benefits over other conventional tumor models, and have the potential to accelerate drug discovery and enable precision medicines. However, further research is warranted to overcome their limitations and to properly interpret the data obtained from these models. In this article, key features of the in vivo tumor microenvironment that are relevant to drug transport processes for targeted delivery was discussed, and the current status and challenges for developing in vitro transport model systems was reviewed.
Tubular Human Brain Organoids to Model Microglia-Mediated Neuroinflammation
(Royal Society of Chemistry, 2021) Ao, Zheng; Cai, Hongwei; Wu, Zhuhao; Song, Sunghwa; Karahan, Hande; Kim, Byungwook; Lu, Hui-Chen; Kim, Jungsu; Mackie, Ken; Guo, Feng; Medical and Molecular Genetics, School of Medicine
Human brain organoids, 3D brain tissue cultures derived from human pluripotent stem cells, hold promising potential in modeling neuroinflammation for a variety of neurological diseases. However, challenges remain in generating standardized human brain organoids that can recapitulate key physiological features of a human brain. Here, we present a tubular organoids-on-a-chip device to generate better organoids and model neuroinflammation. By employing 3D printed hollow mesh scaffolds, our device can be easily incorporated into multiwell-plates for reliable, scalable, and reproducible generation of tubular organoids. By introducing rocking flows through the tubular device channel, our device can perfuse nutrients and oxygen to minimize organoid necrosis and hypoxia, and incorporate immune cells into organoids to model neuro-immune interactions. Compared with conventional protocols, our method increased neural progenitor proliferation and reduced heterogeneity of human brain organoids. As a proof-of-concept application, we applied this method to model the microglia-mediated neuroinflammation after exposure to an opioid. We found isogenic microglia were activated after exposure to an opioid receptor agonist (DAMGO) and transformed back to the homeostatic status with further treatment by a cannabinoid receptor 2 agonist (LY2828360). Importantly, the activated microglia in tubular organoids had a stronger cytokine response compared to those in 2D microglial cultures. Our tubular organoid device is simple, versatile, inexpensive, easy-to-use, and compatible with multiwell-plates, so it can be widely used in common research and clinical laboratory settings. This technology can be broadly used for basic and translational applications in inflammatory diseases including substance use disorders, neural diseases, autoimmune disorders, and infectious diseases.

Browsing by Subject "Microfluidics"

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