using-adhesive-patterning-to-construct-3d-paper-microfluidic-devices

Using Adhesive Patterning to Construct 3D Paper Microfluidic Devices

We demonstrate the use of patterned aerosol adhesives to construct both planar and nonplanar 3D paper microfluidic devices. By spraying an aerosol ...

meso-scale-particle-image-velocimetry-studies-neurovascular-flows

Meso-Scale Particle Image Velocimetry Studies of Neurovascular Flows <em>In Vitro</em>

Particle image velocimetry (PIV) is used in a wide variety of fields, due to the opportunity it provides for precisely visualizing and quantifying flows ...

University of California, Riverside

Cell and microparticle separation in microfluidic systems has recently gained significant attention in sample preparations for biological and chemical studies. Microfluidic separation is typically achieved by applying differential forces on the target particles to guide them into different paths. This paper reviews basic concepts and novel designs of such microfluidic separators with emphasis on the use of non-inertial force fields, including dielectrophoretic force, optical gradient force, magnetic force, and acoustic primary radiation force. Comparisons of separation performances with discussions on physiological effects and instrumentation issues toward point-of-care devices are provided as references for choosing appropriate separation methods for various applications.

Cell Separation by Non-Inertial Force Fields in Microfluidic Systems.

CDX2 is associated with the intestinal phenotype in the gastrointestinal tracts and is expressed in the intestinal type of gastric cancer. Helicobacter pylori-associated atrophic gastritis is characterized by aberrant expression of CDX2. The aim was to investigate the effects of eradication to the expression of genes related to the gastric and intestinal phenotype including CDX2. We compared the effect of eradication between the patients at high risk for gastric cancer and controls.

Helicobacter pylori eradication prevents extension of intestinalization even in the high-risk group for gastric cancer.

This paper presents a microfluidic device for sorting embryoid bodies (EBs) with large dynamic size ranges up to 300 microm. The proposed separation scheme utilizes appropriately spaced pillars within a microchannel to alter the fluid flow pathway, thus allowing particles of defined sizes to be diverted towards specific flow paths. We test the device functionality by separating polystyrene beads 90, 175 and 275 microm in diameter, demonstrating separation efficiencies approaching 100%. We then demonstrate for the first time on-chip separation of mouse EBs, which were separated into three size groups. The ability to extract specific size ranges of EBs will greatly facilitate their subsequent differentiation studies.

Continuous sorting of heterogeneous-sized embryoid bodies.

In this study, we have developed an integrated microfluidic platform for actively patterning mammalian cells, where poly(ethylene glycol) (PEG) hydrogels play two important roles as a non-fouling layer and a dielectric structure. The developed system has an embedded array of PEG microwells fabricated on a planar indium tin oxide (ITO) electrode. Due to its dielectric properties, the PEG microwells define electrical energy landscapes, effectively forming positive dielectrophoresis (DEP) traps in a low-conductivity environment. Distribution of DEP forces on a model cell was first estimated by computationally solving quasi-electrostatic Maxwell's equations, followed by an experimental demonstration of cell and particle patterning without an external flow. Furthermore, efficient patterning of mouse embryonic stem (mES) cells was successfully achieved in combination with an external flow. With a seeding density of 10⁷ cells/mL and a flow rate of 3 μL/min, trapping of cells in the microwells was completed in tens of seconds after initiation of the DEP operation. Captured cells subsequently formed viable and homogeneous monolayer patterns. This simple approach could provide an efficient strategy for fabricating various cell microarrays for applications such as cell-based biosensors, drug discovery, and cell microenvironment studies.

Efficient dielectrophoretic patterning of embryonic stem cells in energy landscapes defined by hydrogel geometries.

A major challenge in stem cell-mediated regenerative medicine is the development of defined culture systems for the maintenance of clinical-grade human embryonic stem (hES) cells. Here, we identify, using a feedback system control scheme, a unique combination of three small molecule inhibitors that enables the maintenance of hES cells on a fibronectin-coated surface through single cell passaging. After 20 passages, the undifferentiated state of the hES cells was confirmed by OCT4, SSEA4 and NANOG expressions, whereas their pluripotent potential and genetic integrity were demonstrated by teratoma formation and normal karyotype, respectively. Our study attests to the power of the feedback system control scheme to quickly pinpoint optimal conditions for desired biological activities, and provides a chemically defined, scalable and single cell passaging culture system for hES cells.

An optimized small molecule inhibitor cocktail supports long-term maintenance of human embryonic stem cells.

Human pluripotent stem cells hold promising potential in many therapeutics applications including regenerative medicine and drug discovery. Over the past three decades, embryonic stem cell research has illustrated that embryonic stem cells possess two important and distinct properties: the ability to continuously self-renew and the ability to differentiate into all specialized cell types. In this article, we will discuss the continuing evolution of human pluripotent stem cell culture by examining requirements needed for the maintenance of self-renewal in vitro. We will also elaborate on the future direction of the field toward generating a robust and completely defined culture system, which has brought forth collaborations amongst biologists and engineers. As human pluripotent stem cell research progresses towards identifying solutions for debilitating diseases, it will be critical to establish a defined, reproducible and scalable culture system to meet the requirements of these clinical applications.

Developing defined culture systems for human pluripotent stem cells.

Barrett's esophagus with specialized intestinal metaplasia (SIM), which is at high risk of progressing to esophageal adenocarcinoma, has been identified by obtaining biopsy specimens randomly. Magnified endoscopy with narrow band imaging (ME-NBI) is reported to be useful for detecting SIM or the intestinal phenotype. We aimed to evaluate the usefulness of endoscopic brushing followed by ME-NBI for the detection of the intestinal phenotype.

Usefulness of endoscopic brushing and magnified endoscopy with narrow band imaging (ME-NBI) to detect intestinal phenotype in columnar-lined esophagus.

Patients with gastroesophageal reflux disease (GERD) also have various extra-esophageal symptoms. Laryngopharyngeal reflux disease (LPRD) is a subtype of GERD associated with globus sensation, but proton pump inhibitor (PPI) therapy achieves disappointing results. This study investigated esophageal motility in GERD patients with globus sensation who were resistant to PPI therapy.

Esophageal motor dysfunction plays a key role in GERD with globus sensation--analysis of factors promoting resistance to PPI therapy.

The survival, growth, self-renewal, and differentiation of human pluripotent stem cells (hPSCs) are influenced by their microenvironment, or so-called "niche," consisting of particular chemical and physical cues. Previous studies on mesenchymal stem cells and other stem cells have collectively uncovered the importance of physical cues and have begun to shed light on how stem cells sense and process such cues. In an attempt to support similar progress in mechanobiology of hPSCs, we review mechanosensory machinery, which plays an important role in cell-extracellular matrix interactions, cell-cell interactions, and subsequent intracellular responses. In addition, we review recent studies on the mechanobiology of hPSCs, in which engineered micromechanical environments were used to investigate effects of specific physical cues. Identifying key physical cues and understanding their mechanism will ultimately help in harnessing the full potential of hPSCs for clinical applications.

Engineered micromechanical cues affecting human pluripotent stem cell regulations and fate.

Advancements in biomedical micro/nano tools and technology.

This article discusses the fabrication of planar and nonplanar 3D paper microfluidic circuits through the use of patterned spray adhesive application and origami techniques. The individual paper layers are held together via semi-permanent adhesive bonds without the need for external clamps. Semi-permanent bonds accommodate the repeated folding and unfolding required by complex origami device structures and allow the device to be unfolded post-use to view internally displayed results. Combinations of adhesive patterns and fluid channel widths were identified that did not prevent the fluid from traveling between layers and through the entire circuit. Further, this method was extended to nonplanar 3D paper microfluidic circuits, demonstrated via multi-fluid wicking within a modified origami peacock. Such nonplanar 3D paper microfluidic circuits are expected to offer an entirely new platform for exploring new designs and functions of paper analytical devices.

Patterned adhesive enables construction of nonplanar three-dimensional paper microfluidic circuits.

Low-cost and quick detection of biotic stresses is critically important for protection of staple food crops such as maize in smallholder farms in developing countries, where access to improved seed varieties, fertilizers, and pesticides is limited due to financial and geographical reasons. Here, we report a new lateral flow detection technology directly integrated in a maize leaf, in which microspheres conjugated with analyte-specific capture antibodies are non-invasively injected. The antibody-conjugated microspheres capture and detect an analyte in a concentration-specific manner. In this study, we optimized microsphere size for effective infiltration and immobilization in the leaf, and further demonstrated detection of a fluorescent mock biomarker, fluorescein, in a live maize plant. This in planta lateral flow biosensor is the first of its kind and is expected to provide a low-cost and user-friendly detection method for biotic stresses in the field.

In Planta Microsphere-Based Lateral Flow Leaf Biosensor in Maize.

"Globus sensation" is often described as the sensation of a lump in the throat associated with dry swallowing or the need for dry swallowing, which disappears completely during eating or drinking and for which no organic cause can be established. Due to the uncertain etiology of "globus sensation", it remains difficult to establish standard treatment strategies for affected patients. Lately most attention has been focused on gastroesophageal reflux disease and several reports have indicated that there is a close relationship between esophageal acid reflux and globus sensation. Nowadays, empirical therapy with a high dose of a proton pump inhibitor (PPI) is considered to be indicated for patients with globus sensation, after excluding organic diseases such as pharyngeal cancer, Zenker's diverticulum, or thyroid enlargement. If patients are nonresponsive to PPI therapy, evaluation of esophageal motility should be done. In our recent study, 47.9% had abnormal esophageal motility, with the most common esophageal motility abnormality being an ineffective esophageal motility in PPI-resistant patients with globus sensation. This suggests that prokinetics alone or adding prokinetics to PPI should be the treatment to be considered, although few studies have investigated the efficacy of prokinetics in the treatment of patients with globus sensation. If patients without any esophageal motility dysfunctions are nonresponsive to PPI therapy, either cognitive-behavioral therapy, anti-depressants, or gabapentin could be helpful, although further well-designed, randomized controlled large-scale studies will be necessary to determine the effectiveness of each treatment strategy on patients with globus sensation.

ArticleTotal : 2	Year
Publication title Cited by 4	2016
Publication title	2018

Article	Year
Cell Separation by Non-Inertial Force Fields in Microfluidic Systems. Mechanics research communications\| PubMed ID: 20046897	2009
Helicobacter pylori eradication prevents extension of intestinalization even in the high-risk group for gastric cancer. Digestion\| PubMed ID: 20110706	2010
Continuous sorting of heterogeneous-sized embryoid bodies. Lab on a chip\| PubMed ID: 20376391	2010
Efficient dielectrophoretic patterning of embryonic stem cells in energy landscapes defined by hydrogel geometries. Annals of biomedical engineering\| PubMed ID: 20614250	2010
An optimized small molecule inhibitor cocktail supports long-term maintenance of human embryonic stem cells. Nature communications\| PubMed ID: 21266967	2011
Developing defined culture systems for human pluripotent stem cells. Regenerative medicine\| PubMed ID: 21916597	2011
Usefulness of endoscopic brushing and magnified endoscopy with narrow band imaging (ME-NBI) to detect intestinal phenotype in columnar-lined esophagus. Journal of gastroenterology\| PubMed ID: 22576025	2012
Esophageal motor dysfunction plays a key role in GERD with globus sensation--analysis of factors promoting resistance to PPI therapy. Scandinavian journal of gastroenterology\| PubMed ID: 22594305	2012
Engineered micromechanical cues affecting human pluripotent stem cell regulations and fate. Journal of laboratory automation\| PubMed ID: 24062363	2013
Advancements in biomedical micro/nano tools and technology. Journal of laboratory automation\| PubMed ID: 24067618	2013
Patterned adhesive enables construction of nonplanar three-dimensional paper microfluidic circuits. Lab on a chip\| PubMed ID: 25222567	2014
In Planta Microsphere-Based Lateral Flow Leaf Biosensor in Maize. Journal of laboratory automation\| PubMed ID: 25271045	2015
Pathophysiology and treatment of patients with globus sensation--from the viewpoint of esophageal motility dysfunction. Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi\| PubMed ID: 26081369	2014

Hideaki Tsutsui

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