Publications by authors named "Arum Han"

85 Publications

Organic Anion Transporting Polypeptide 2B1 in Human Fetal Membranes: A Novel Gatekeeper for Drug Transport During Pregnancy?

Front Pharmacol 2021 20;12:771818. Epub 2021 Dec 20.

Division of Basic and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, United States.

Current intervention strategies have not been successful in reducing the risks of adverse pregnancy complications nor maternal and fetal morbidities associated with pregnancy complications. Improving pregnancy and neonatal outcomes requires a better understanding of drug transport mechanisms at the feto-maternal interfaces, specifically the placenta and fetal membrane (FM). The role of several solute carrier uptake transporter proteins (TPs), such as the organic anion transporting polypeptide 2B1 (OATP2B1) in transporting drug across the placenta, is well-established. However, the mechanistic role of FMs in this drug transport has not yet been elucidated. We hypothesize that human FMs express OATP2B1 and functions as an alternate gatekeeper for drug transport at the feto-maternal interface. We determined the expression of OATP2B1 in term, not-in-labor, FM tissues and human FM cells [amnion epithelial cell (AEC), chorion trophoblast cell (CTC), and mesenchymal cells] using western blot analyses and their localization using immunohistochemistry. Changes in OATP2B1 expression was determined for up to 48 h after stimulation with cigarette smoke extract (CSE), an inducer of oxidative stress. The functional role of OATP2B1 was determined by flow cytometry using a zombie violet dye substrate assay. After OATP2B1 gene silencing, its functional relevance in drug transport through the feto-maternal interface was tested using a recently developed feto-maternal interface organ-on-a-chip (OOC) system that contained both FM and maternal decidual cells. Propagation of a drug (Rosuvastatin, that can be transported by OATP2B1) within the feto-maternal interface OOC system was determined by mass spectrometry. FMs express OATP2B1 in the CTC and AEC layers. In FM explants, OATP2B1 expression was not impacted by oxidative stress. Uptake of the zombie violet dye within AECs and CTCs showed OATP2B1 is functionally active. Silencing OATP2B1 in CTCs reduced Rosuvastatin propagation from the decidua to the fetal AEC layer within the feto-maternal interface-OOC model. Our data suggest that TPs in FMs may function as a drug transport system at the feto-maternal interface, a function that was previously thought to be performed exclusively by the placenta. This new knowledge will help improve drug delivery testing during pregnancy and contribute to designing drug delivery strategies to treat adverse pregnancy outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.771818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721670PMC
December 2021

Generation and characterization of human Fetal membrane and Decidual cell lines for reproductive biology experiments†.

Biol Reprod 2021 Dec 22. Epub 2021 Dec 22.

Division of Maternal-Fetal Medicine and Perinatal Research, Department of Obstetrics and Gynaecology, The University of Texas Medical Branch at Galveston, Galveston, Texas, USA.

Human fetal membrane and maternal decidua parietalis form one of the major feto-maternal interfaces during pregnancy. Studies on this feto-maternal interface is limited as several investigators have limited access to the placenta, and experience difficulties to isolate and maintain primary cells. Many cell lines that are currently available do not have the characteristics or properties of their primary cells of origin. Therefore, we created, characterized the immortalized cells from primary isolates from fetal membrane-derived amnion epithelial cells, amnion and chorion mesenchymal cells, chorion trophoblast cells and maternal decidua parietalis cells. Primary cells were isolated from a healthy full-term, not in labor placenta. Primary cells were immortalized using either a HPV16E6E7 retroviral or a SV40T lentiviral system. The immortalized cells were characterized for the morphology, cell type-specific markers, and cell signalling pathway activation. Genomic stability of these cells was tested using RNA seq, karyotyping, and short tandem repeats DNA analysis. Immortalized cells show their characteristic morphology, and express respective epithelial, mesenchymal and decidual markers similar to that of primary cells. Gene expression of immortalized and primary cells were highly correlated (R = 0.798 to R = 0.974). Short tandem repeats DNA analysis showed in the late passage number (>P30) of cell lines matched 84-100% to the early passage number (
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/biolre/ioab231DOI Listing
December 2021

Biomedical microdevices: the next phase of highlighting scientific discoveries in the field of micro-nanotechnologies for medicine.

Biomed Microdevices 2021 Nov 16;24(1). Epub 2021 Nov 16.

Department of Electrical and Computer Engineering, Texas A&M University, Houston, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10544-021-00601-zDOI Listing
November 2021

Development of single-cell-level microfluidic technology for long-term growth visualization of living cultures of .

Microsyst Nanoeng 2021 20;7:37. Epub 2021 May 20.

Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX 77843 USA.

Analysis of growth and death kinetics at single-cell resolution is a key step in understanding the complexity of the nonreplicating growth phenotype of the bacterial pathogen . Here, we developed a single-cell-resolution microfluidic mycobacterial culture device that allows time-lapse microscopy-based long-term phenotypic visualization of the live replication dynamics of mycobacteria. This technology was successfully applied to monitor the real-time growth dynamics of the fast-growing model strain () while subjected to drug treatment regimens during continuous culture for 48 h inside the microfluidic device. A clear morphological change leading to significant swelling at the poles of the bacterial membrane was observed during drug treatment. In addition, a small subpopulation of cells surviving treatment by frontline antibiotics was observed to recover and achieve robust replicative growth once regular culture media was provided, suggesting the possibility of identifying and isolating nonreplicative mycobacteria. This device is a simple, easy-to-use, and low-cost solution for studying the single-cell phenotype and growth dynamics of mycobacteria, especially during drug treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41378-021-00262-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433163PMC
May 2021

A scalable system for generation of mesenchymal stem cells derived from induced pluripotent cells employing bioreactors and degradable microcarriers.

Stem Cells Transl Med 2021 12 10;10(12):1650-1665. Epub 2021 Sep 10.

Department of Biomedical Engineering, Texas A&M University, Emerging Technologies Building, College Station, Texas, USA.

Human mesenchymal stem cells (hMSCs) are effective in treating disorders resulting from an inflammatory or heightened immune response. The hMSCs derived from induced pluripotent stem cells (ihMSCs) share the characteristics of tissue derived hMSCs but lack challenges associated with limited tissue sources and donor variation. To meet the expected future demand for ihMSCs, there is a need to develop scalable methods for their production at clinical yields while retaining immunomodulatory efficacy. Herein, we describe a platform for the scalable expansion and rapid harvest of ihMSCs with robust immunomodulatory activity using degradable gelatin methacryloyl (GelMA) microcarriers. GelMA microcarriers were rapidly and reproducibly fabricated using a custom microfluidic step emulsification device at relatively low cost. Using vertical wheel bioreactors, 8.8 to 16.3-fold expansion of ihMSCs was achieved over 8 days. Complete recovery by 5-minute digestion of the microcarriers with standard cell dissociation reagents resulted in >95% viability. The ihMSCs matched or exceeded immunomodulatory potential in vitro when compared with ihMSCs expanded on monolayers. This is the first description of a robust, scalable, and cost-effective method for generation of immunomodulatory ihMSCs, representing a significant contribution to their translational potential.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/sctm.21-0151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8641084PMC
December 2021

Physical distancing messages targeting youth on the social media accounts of Canadian public health entities and the use of behavioral change techniques.

BMC Public Health 2021 09 7;21(1):1634. Epub 2021 Sep 7.

School of Epidemiology and Public Health (SEPH), Faculty of Medicine, University of Ottawa, Ottawa, Canada.

Introduction: Physical distancing (PD) is an important public health strategy to reduce the transmission of COVID-19 and has been promoted by public health authorities through social media. Although youth have a tendency to engage in high-risk behaviors that could facilitate COVID-19 transmission, there is limited research on the characteristics of PD messaging targeting this population on social media platforms with which youth frequently engage. This study examined social media posts created by Canadian public health entities (PHEs) with PD messaging aimed at youth and young adults aged 16-29 years and reported behavioral change techniques (BCTs) used in these posts.

Methods: A content analysis of all social media posts of Canadian PHEs from Facebook, Twitter, Instagram and YouTube were conducted from April 1st to May 31st, 2020. Posts were classified as either implicitly or explicitly targeting youth and young adults. BCTs in social media posts were identified and classified based on Behavior Change Technique Taxonomy version 1 (BCTTv1). Frequency counts and proportions were used to describe the data.

Results: In total, 319 youth-targeted PD posts were identified. Over 43% of the posts originated from Ontario Regional public health units, and 36.4 and 32.6% of them were extracted from Twitter and Facebook, respectively. Only 5.3% of the total posts explicitly targeted youth. Explicit posts were most frequent from federal PHEs and posted on YouTube. Implicit posts elicited more interactions than explicit posts regardless of jurisdiction level or social media format. Three-quarters of the posts contained at least one BCT, with a greater portion of BCTs found within implicit posts (75%) than explicit posts (52.9%). The most common BCTs from explicit posts were instructions on how to perform a behavior (25.0%) and restructuring the social environment (18.8%).

Conclusions: There is a need for more PD messaging that explicitly targets youth. BCTs should be used when designing posts to deliver public health messages and social media platforms should be selected depending on the target population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12889-021-11659-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422061PMC
September 2021

Fabrication methods for a gel-based separation-free device for whole blood glucose detection.

MethodsX 2021 20;8:101236. Epub 2021 Jan 20.

Department of Electrical and Computer engineering, Texas A&M University, College Station, Texas 77843, USA.

In this paper, we describe two fabrication methods (well array-based and biopsy punching-based) of gel disks to construct a gel-based point-of-care (POC) diagnosis device for direct colorimetric measurement of human whole blood glucose without any extra blood separation step. The gel disks are made of Polyethylene glycol (PEG) diacrylate (PEG-DA) containing immobilized glucose colorimetric assay reagents. The performances of three types of PEG-DA gel (molecular weight: 575, 3,400, and 10,000) based sensors as well as the two fabrication methods were investigated.•The fabricated devices enabled colorimetric whole blood glucose sensing assay without the need for blood cell separation•The biopsy punching-based gel disk fabrication method provided less variation on the fabricated gel disks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mex.2021.101236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374154PMC
January 2021

Molecular mechanisms of environmental toxin cadmium at the feto-maternal interface investigated using an organ-on-chip (FMi-OOC) model.

J Hazard Mater 2022 01 2;422:126759. Epub 2021 Aug 2.

Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX, USA. Electronic address:

Human labor is associated with feto-maternal-derived signals that coordinate to initiate delivery. Exposure to environmental chemicals can prematurely trigger labor-initiating signals at the feto-maternal interface (FMi: decidua, amniochorion), leading to spontaneous preterm birth (PTB). Testing the association between environmental chemical exposure and PTB is difficult due to many limitations in vivo or in vitro. Physiological organ-on-chips (OOCs) are potential alternatives for studying mechanisms leading to PTB. The presented study tested the effect of maternal exposure to cadmium (Cd), an environmental toxin, using the FMi-OOC that incorporates maternal decidua cells and three different fetal cells (chorion, amnion mesenchymal, and amnion epithelial cells). Cd transport through the FMi and its impact on cell cycle, cell death, and inflammation were analyzed. Cd treatment resulted in significant cell death and a pro-inflammatory environment in the maternal decidua, but had minimal effect on the fetal chorion cells, and no effect in the fetal amnion cells compared to controls. The maternal response, but lack of fetal response, indicates that Cd-mediated adverse effects originate from maternal pathophysiology rather than fetal-derived triggers of preterm labor. This study demonstrates that the FMi-OOC can indeed predict the response of FMi upon exposure to chemicals, opening the possibility for using OOC models for environmental toxin screens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhazmat.2021.126759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595660PMC
January 2022

Cell Washing and Solution Exchange in Droplet Microfluidic Systems.

Anal Chem 2021 06 10;93(24):8622-8630. Epub 2021 Jun 10.

Department of Electrical and Computer Engineering, Texas A&M University, College Station, Texas 77843, United States.

Water-in-oil emulsion droplet microfluidic systems have been extensively developed, and currently, almost all cell handling steps can be conducted in this format. An exception is the cell washing and solution exchange step, which is commonly utilized in many conventional cell assays. This paper presents an in-droplet cell washing and solution exchange technology that utilizes dielectrophoretic (DEP) force to move all cells to one side of a droplet, followed by asymmetrical splitting of the droplet to obtain a small daughter droplet that contains all or most of the cells, and then finally merges this cell-concentrated droplet with a new droplet that contains the desired solution. These sequential droplet manipulation steps were integrated into a single platform, where up to 88% of the original solution in the droplet could be exchanged with the new solution while keeping cell loss to less than 5%. Two application examples were demonstrated using the developed technology. In the first example, green microalga cells were manipulated using negative DEP force to exchange the regular culture medium with a nitrogen-limited medium to induce lipid production. In the second example, cells were manipulated using positive DEP force to replace fluorescent dye that models fluorescent cell stains that contribute to high background noise in fluorescence-based droplet content detection with fresh buffer solution, significantly improving the droplet content detection sensitivity. Since the cell washing step is one of the most frequently utilized steps in many cell biology assays, we expect that the developed technology can significantly broaden the type of assay that can be conducted in droplet microfluidic format.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.analchem.1c01558DOI Listing
June 2021

Extracellular vesicle mediated feto-maternal HMGB1 signaling induces preterm birth.

Lab Chip 2021 05;21(10):1956-1973

Division of Maternal-Fetal Medicine and Perinatal Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, 301 University Blvd., Galveston, TX 77555-1062, USA.

Preterm birth (PTB; <37 weeks of gestation) impacts ∼11% of all pregnancies and contributes to 1 million neonatal deaths worldwide annually. An understanding of the feto-maternal (F-M) signals that initiate birthing (parturition) at term is critical to design strategies to prevent their premature activation, resulting in PTB. Although endocrine and immune cell signaling are well-reported, fetal-derived paracrine signals capable of transitioning quiescent uterus to an active state of labor are poorly studied. Recent reports have suggested that senescence of the fetal amnion membrane coinciding with fetal growth and maturation generates inflammatory signals capable of triggering parturition. This is by increasing the inflammatory load at the feto-maternal interface (FMi) tissues (i.e., amniochorion-decidua). High mobility group box 1 protein (HMGB1), an alarmin, is one of the inflammatory signals released by senescent amnion cells via extracellular vesicles (exosomes; 40-160 nm). Increased levels of HMGB1 in the amniotic fluid, cord and maternal blood are associated with term and PTB. This study tested the hypothesis that senescent amnion cells release HMGB1, which is fetal signaling capable of increasing FMi inflammation, predisposing them to parturition. To test this hypothesis, exosomes from amnion epithelial cells (AECs) grown under normal conditions were engineered to contain HMGB1 by electroporation (eHMGB1). eHMGB1 was characterized (quantity, size, shape, markers and loading efficiency), and its propagation through FMi was tested using a four-chamber microfluidic organ-on-a-chip device (FMi-OOC) that contained four distinct cell types (amnion and chorion mesenchymal, chorion trophoblast and decidual cells) connected through microchannels. eHMGB1 propagated through the fetal cells and matrix to the maternal decidua and increased inflammation (receptor expression [RAGE and TLR4] and cytokines). Furthermore, intra-amniotic injection of eHMGB1 (containing 10 ng) into pregnant CD-1 mice on embryonic day 17 led to PTB. Injecting carboxyfluorescein succinimidyl ester (CFSE)-labeled eHMGB1, we determined in vivo kinetics and report that eHMGB1 trafficking resulting in PTB was associated with increased FMi inflammation. This study determined that fetal exosome mediated paracrine signaling can generate inflammation and induce parturition. Besides, in vivo functional validation of FMi-OOC experiments strengthens the reliability of such devices to test physiologic and pathologic systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0lc01323dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162392PMC
May 2021

Tomographic similarity scan with a computed modified absolute mandibular midsagittal plane for precise and objective localization of mandibular asymmetry.

Comput Biol Med 2021 07 4;134:104465. Epub 2021 May 4.

Department of Orthodontics, Institute of Craniofacial Deformity, Yonsei University College of Dentistry, Seoul, 03722, Republic of Korea. Electronic address:

The application of 3D imaging is at its cusp in craniofacial diagnosis and treatment planning. However, most applications are limited to simple subjective superimposition-based analysis. As the diagnostic accuracy dictates the precision in operability, we propose a novel method that enables objective clinical decision making for patients with mandibular asymmetry. We analyzed cone-beam computed tomography (CBCT) scans of 34 patients who underwent surgical correction for mandibular asymmetry using a high-throughput computing algorithm. Radiomic segmentation of quantitative features of surface and volume followed by exploration resulted in identification of a computed modified absolute mandibular midsagittal plane (cmAMP). Tomographic similarity scan (ToSS) curves were generated via bilateral equidistant scanning in an antero-posterior direction with cmAMP as the reference. ToSS comprised of a comprehensive similarity index (SI) score curve and a segment-wise volume curve. The SI score was computed using the Sørensen-Dice similarity coefficient ranging from 0 to 1. The volumetric analysis was represented as the non-overlapping volume (NOV) and overlapping volume (OV) for each segment, with two segmentation lines, at the mental foramen anteriorly and the intraoral vertical ramus osteotomy region posteriorly. Statistical analysis showed strong negative correlation between the NOV and SI scores for the anterior, middle, and total mandible (P < 0.001). Additionally, a significant correlation was observed between the change in the SI scores for anterior (P = 0.044) and middle segments (P < 0.001) to the total mandible when comparing the data before and after the surgery. This work demonstrated the potential of incorporating ToSS curves in surgical simulation software to improve precision in the clinical decision-making process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.compbiomed.2021.104465DOI Listing
July 2021

Organ-on-chip of the cervical epithelial layer: A platform to study normal and pathological cellular remodeling of the cervix.

FASEB J 2021 04;35(4):e21463

Division of Maternal-Fetal Medicine and Perinatal Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, USA.

Damage to the cervical epithelial layer due to infection and inflammation is associated with preterm birth. However, the individual and/or collective roles of cervical epithelial layers in maintaining cervical integrity remain unclear during infection/inflammation. To determine the intercellular interactions, we developed an organ-on-chip of the cervical epithelial layer (CE-OOC) composed of two co-culture chambers connected by microchannels, recapitulating the ectocervical and endocervical epithelial layers. Further, we tested the interactions between cells from each distinct region and their contributions in maintaining cervical integrity in response to LPS and TNFα stimulations. The co-culture of ectocervical and endocervical cells facilitated cellular migration of both epithelial cells inside the microchannels. Compared to untreated controls, both LPS and TNFα increased apoptosis, necrosis, and senescence as well as increased pro-inflammatory cytokine productions by cervical epithelial cells. In summary, the CE-OOC established an in vitro model that can recapitulate the ectocervical and the endocervical epithelial regions of the cervix. The established CE-OOC may become a powerful tool in obstetrics and gynecology research such as in studying cervical remodeling during pregnancy and parturition and the dynamics of cervical epithelial cells in benign and malignant pathology in the cervix.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1096/fj.202002590RRRDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193817PMC
April 2021

Sub-second heat inactivation of coronavirus using a betacoronavirus model.

Biotechnol Bioeng 2021 05 3;118(5):2067-2075. Epub 2021 Mar 3.

Department of Electrical and Computer Engineering, Texas A&M University, College Station, Texas, USA.

Heat treatment denatures viral proteins that comprise the virion, making the virus incapable of infecting a host. Coronavirus (CoV) virions contain single-stranded RNA genomes with a lipid envelope and four proteins, three of which are associated with the lipid envelope and thus are thought to be easily denatured by heat or surfactant-type chemicals. Prior studies have shown that a temperature as low as 75°C with a treatment duration of 15 min can effectively inactivate CoV. The degree of CoV heat inactivation greatly depends on the length of heat treatment time and the temperature applied. With the goal of finding whether sub-second heat exposure of CoV can sufficiently inactivate CoV, we designed and developed a simple fluidic system that can measure sub-second heat inactivation of CoV. The system is composed of a stainless-steel capillary immersed in a temperature-controlled oil bath followed by an ice bath, through which virus solution can flow at various speeds. Flowing virus solution at different speeds, along with temperature control and monitoring system, allows the virus to be exposed to the desired temperature and treatment durations with high accuracy. Using mouse hepatitis virus, a betacoronavirus, as a model CoV system, we identified that 71.8°C for 0.51 s exposure is sufficient to obtain >5 Log reduction in viral titer (starting titer: 5 × 10 PFU/ml), and that when exposed to 83.4°C for 1.03 s, the virus was completely inactivated (>6 Log reduction).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/bit.27720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013827PMC
May 2021

A Gel-Based Separation-Free Point-of-Care Device for Whole Blood Glucose Detection.

Anal Chem 2020 12 2;92(24):16122-16129. Epub 2020 Nov 2.

Department of Electrical and Computer Engineering, Texas A&M University, College Station, Texas 77843, United States.

This article introduces a gel-based separation-free point-of-care (POC) device for whole blood glucose colorimetric detection. Enzymes and a chromogenic substrate needed for colorimetric detection of glucose were entrapped in a photopolymerized poly(ethylene) glycol diacrylate (PEG-DA) hydrogel that was cast-molded into a circular shape. Our method enables colorimetric detection without the need for preseparation of blood plasma as the nanometer-scale three-dimensional porous structure of the hydrogel allows the diffusion of small analytes such as glucose while blocking the much larger blood cells. Our method requires less enzymatic concentration and, hence, offers a cost-saving benefit. In addition, PEG-DA also acts as an enzyme stabilizer, and the shelf-life testing result shows that enzyme activity can be maintained in PEG-DA over a long period of time. The concept of this simple, cost-effective method was demonstrated by the colorimetric detection of blood glucose directly from human whole bloodthout any sample preparation steps. The results were compared with those of a spectrophotometry method and showed relative error ranging from 5 to 19%, and less than 9% when compared with a commercial glucose meter. The presented method has the potential to be broadly utilized for other whole blood biomolecule analyses in POC testing applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.analchem.0c03801DOI Listing
December 2020

Modeling ascending infection with a feto-maternal interface organ-on-chip.

Lab Chip 2020 11;20(23):4486-4501

Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine & Perinatal Research, The University of Texas Medical Branch at Galveston, 301 University Blvd., Galveston, TX 77555-1062, USA.

Maternal infection (i.e., ascending infection) and the resulting host inflammatory response are risk factors associated with spontaneous preterm birth (PTB), a major pregnancy complication. However, the path of infection and its propagation from the maternal side to the fetal side have been difficult to study due to the lack of appropriate in vitro models and limitations of animal models. A better understanding of the propagation kinetics of infectious agents and development of the host inflammatory response at the feto-maternal (amniochorion-decidua, respectively) interface (FMi) is critical in curtailing host inflammatory responses that can lead to PTB. To model ascending infection and determine inflammatory responses at the FMi, we developed a microfluidic organ-on-chip (OOC) device containing primary cells from the FMi (decidua, chorion, and amnion [mesenchyme and epithelium]) and collagen matrix harvested from primary tissue. The FMi-OOC is composed of four concentric circular cell/collagen chambers designed to mimic the thickness and cell density of the FMi in vivo. Each layer is connected by arrays of microchannels filled with type IV collagen to recreate the basement membrane of the amniochorion. Cellular characteristics (viability, morphology, production of nascent collagen, cellular transitions, and migration) in the OOC were similar to those seen in utero, validating the physiological relevance and utility of the developed FMi-OOC. The ascending infection model of the FMi-OOC, triggered by exposing the maternal (decidua) side of the OOC to lipopolysaccharide (LPS, 100 ng mL-1), shows that LPS propagated through the chorion, amnion mesenchyme, and reached the fetal amnion within 72 h. LPS induced time-dependent and cell-type-specific pro-inflammatory cytokine production (24 h decidua: IL-6, 48 h chorion: GM-CSF and IL-6, and 72 h amnion mesenchyme and epithelium: GM-CSF and IL-6). Collectively, this OOC model and study successfully modeled ascending infection, its propagation, and distinct inflammatory response at the FMi indicative of pathologic pathways of PTB. This OOC model provides a novel platform to study physiological and pathological cell status at the FMi, and is expected to have broad utility in the field of obstetrics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0lc00875cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815379PMC
November 2020

Eliminating air bubble in microfluidic systems utilizing integrated in-line sloped microstructures.

Biomed Microdevices 2020 10 22;22(4):76. Epub 2020 Oct 22.

Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX, 77843, USA.

In most microfluidic systems, formation and accumulation of air and other gas bubbles can be detrimental to their operation. Air bubbles in a microfluidic channel induce a pressure profile fluctuation and therefore disturb the stability of the system. Once an air bubble is generated, it is also extremely difficult to remove such bubbles from the microfluidic systems. In tissue and cell culture microfluidic systems, a single air bubble can completely shear off cells that are being cultured. Air bubbles can be especially problematic in microfluidic systems that have to operate for long periods of time, since completely eliminating the generation of air bubbles for prolonged periods of time, where a single air bubble can ruin an entire multi-day/multi-week experiment, is extremely challenging. Several in-line and off-chip bubble traps have been developed so far, but cannot completely eliminate air bubbles from the system or are relatively difficult to integrate into microfluidic systems. Recent advancements in two-photon polymerization (2PP)-based microfabrication method eliminates the restriction in Z-axis control in conventional two-dimensional microfabrication methods, and thus enables complex 3D structures to be fabricated at sub-micrometer resolution. In this work, by utilizing this 2PP technique, we developed a sloped microfluidic structure that is capable of both trapping and real-time removal of air bubbles from the system in a consistent and reliable manner. The novel structures and designs developed in this work present a unique opportunity to overcome many limitations of current methods, bring state-of-the-art solutions in air bubble removal, and enable a multifunctional microfluidic device to operate seamlessly free from air bubble disruption. The microfabricated system was tested in both droplet microfluidics and continuous-flow microfluidics applications, and demonstrated to be effective in preventing air bubble aggregation over time. This simple sloped microstructure can be easily integrated into broad ranges of microfluidic devices to minimize bubble introduction, which will contribute to creating a stable and bubble-free microfluidic platform amenable for long-term operation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10544-020-00529-wDOI Listing
October 2020

An ultra high-efficiency droplet microfluidics platform using automatically synchronized droplet pairing and merging.

Lab Chip 2020 11 16;20(21):3948-3959. Epub 2020 Sep 16.

Department of Electrical and Computer Engineering, Texas A&M University, College Station, Texas 77843, USA.

Droplet microfluidics systems hold great promise in their ability to conduct high-throughput assays for a broad range of life science applications. Despite their promise in the field and capability to conduct complex liquid handling steps, currently, most droplet microfluidic systems used for real assays utilize only a few droplet manipulation steps connected in series, and are often not integrated together on a single chip or platform. This is due to the fact that linking multiple sequential droplet functions within a single chip to operate at high efficiency over long periods of time remains technically challenging. Considering sequential manipulation is often required to conduct high-throughput screening assays on large cellular and molecular libraries, advancements in sequential operation and integration are required to advance the field. This current limitation greatly reduces the type of assays that can be realized in a high-throughput droplet format and becomes more prevalent in large library screening applications. Here we present an integrated multi-layer droplet microfluidic platform that can handle large numbers of droplets with high efficiency and minimum error. The platform combines two-photon photolithography-fabricated curved microstructures that allow high-efficiency (99.9%) re-flow of droplets and a unique droplet cleaving that automatically synchronizes paired droplets enabling high-efficiency (99.9%) downstream merging. We demonstrate that this method is applicable to a broad range of droplet sizes, including relatively large droplet sizes (hundreds of micrometers in diameter) that are typically more difficult to manipulate with high efficiency, yet are required in many cell assay applications requiring large organisms or multiple incubation steps. The utility of this highly efficient integrated droplet microfluidic platform was demonstrated by conducting a mock antibiotic screening assay against a bacterial pathogen. The approach and system presented here provides new avenues for the realization of ultra-high-efficiency multi-step droplet microfluidic systems with minimal error.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0lc00757aDOI Listing
November 2020

In-droplet cell separation based on bipolar dielectrophoretic response to facilitate cellular droplet assays.

Lab Chip 2020 10 14;20(20):3832-3841. Epub 2020 Sep 14.

Department of Electrical and Computer Engineering, Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, USA.

Precise manipulation of cells within water-in-oil emulsion droplets has the potential to vastly expand the type of cellular assays that can be conducted in droplet-based microfluidics systems. However, achieving such manipulation remains challenging. Here, we present an in-droplet label-free cell separation technology by utilizing different dielectrophoretic responses of two different cell types. Two pairs of angled planar electrodes were utilized to generate positive or negative dielectrophoretic force acting on each cell type, which results in selective in-droplet movement of only one specific cell type at a time. A downstream asymmetric Y-shaped microfluidic junction splits the mother droplet into two daughter droplets, each of which contains only one cell type. The capability of this platform was successfully demonstrated by conducting in-droplet separation from a mixture of Salmonella cells and macrophages, two cell types commonly used as a bacterial pathogenicity analysis model. This technology enable the precise manipulation of cells within droplets, which can be exploited as a critical function in implementing broader ranges of droplet-based microfluidics cellular assays.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0lc00710bDOI Listing
October 2020

High-throughput and label-free multi-outlet cell counting using a single pair of impedance electrodes.

Biosens Bioelectron 2020 Oct 17;166:112458. Epub 2020 Jul 17.

Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX, USA; Department of Biomedical Engineering, Texas A&M University, College Station, TX, USA; Center for Remote Health Technologies and Systems Texas A&M University, College Station, TX, USA. Electronic address:

There are increasing number of cell separation applications where cells needs to be separated into multiple outlets. Quantification of sorted or separated cells and particles in microfluidic systems flowing through multiple outlet channels are typically conducted off-line through microscopic image analysis, or by first collecting cells from each outlet and counting them afterwards. However, these methods do not provide real-time analysis, are time consuming, and can lead to significant error in analysis when handling and collecting a small number of cells (such as rare cells). Here, we present a low-cost, label-free, and real-time on-chip cell counting and quantifying method for sorted/separated cells flowing through multiple microfluidic outlets using only a single pair of microelectrodes. The single staircase-shaped electrode design positioned perpendicular to the outlets subjects cells flowing through different outlets to different electric field strength, thus resulting in different impedance signals depending on which outlets the cell passes through. This design was enhanced by studying and comparing the results of both simulations and experiments. To analyze whether cells passing through each of the five outlets can be correctly classified based on their impedance peak height and width, three different classification methods were tested and compared. The developed design was successfully utilized to distinguish cells flowing through 5 different outlets using only a single pair of impedance electrodes, showing classification error rate of only 1.91%. This single-pair staircase-shaped electrode design can be applied to any cell separation system, regardless of the separation methods utilized, and thus have extremely broad application space in the field of microfluidic cell separation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bios.2020.112458DOI Listing
October 2020

Organ-On-Chip Technology: The Future of Feto-Maternal Interface Research?

Front Physiol 2020 30;11:715. Epub 2020 Jun 30.

Department of Electrical and Computer Engineering, College of Engineering, Texas A&M University, College Station, TX, United States.

The placenta and fetal membrane act as a protective barrier throughout pregnancy while maintaining communication and nutrient exchange between the baby and the mother. Disruption of this barrier leads to various pregnancy complications, including preterm birth, which can have lasting negative consequences. Thus, understanding the role of the feto-maternal interface during pregnancy and parturition is vital to advancing basic and clinical research in the field of obstetrics. However, human subject studies are inherently difficult, and appropriate animal models are lacking. Due to these challenges, cell culture-based studies are most commonly utilized. However, the structure and functions of conventionally used 2D and 3D models are vastly different from the environment, making it difficult to fully understand the various factors affecting pregnancy as well as pathways and mechanisms contributing to term and preterm births. This limitation also makes it difficult to develop new therapeutics. The emergence of -like models such as organ-on-chip (OOC) platforms can better recapitulate functions and responses and has the potential to move this field forward significantly. OOC technology brings together two distinct fields, microfluidic engineering and cell/tissue biology, through which diverse human organ structures and functionalities can be built into a laboratory model that better mimics functions and responses of tissues and organs. In this review, we first provide an overview of the OOC technology, highlight two major designs commonly used in achieving multi-layer co-cultivation of cells, and introduce recently developed OOC models of the feto-maternal interface. As a vital component of this review, we aim to outline progress on the practicality and effectiveness of feto-maternal interface OOC (FM-OOC) models currently used and the advances they have fostered in obstetrics research. Lastly, we provide a perspective on the future basic research and clinical applications of FM-OOC models, and even those that integrate multiple organ systems into a single OOC system that may recreate intrauterine architecture in its entirety, which will accelerate our understanding of feto-maternal communication, induction of preterm labor, drug or toxicant permeability at this vital interface, and development of new therapeutic strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2020.00715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338764PMC
June 2020

Comparison of the predictive validity of three fall risk assessment tools and analysis of fall-risk factors at a tertiary teaching hospital.

J Clin Nurs 2020 Sep 13;29(17-18):3482-3493. Epub 2020 Jul 13.

College of Nursing and Research Institute of Nursing Science, Seoul National University, Seoul, Korea.

Aims And Objectives: The main purpose of this study was to identify the best fall-risk assessment tool, among the Morse Fall Scale, the Johns Hopkins fall-risk Assessment Tool and the Hendrich II fall-risk Model, for a tertiary teaching hospital. The study also analysed fall-risk factors in the hospital, focusing on the items of each fall assessment tool.

Methods: Data on falls were obtained from the patient safety reports and electronic nursing records of a tertiary teaching hospital. A retrospective study was conducted to compare the sensitivity, specificity, area under the curve, positive predictive value, negative predictive value, Youden index and accuracy of the Morse Fall Scale, the Johns Hopkins fall-risk Assessment Tool and the Hendrich II fall-risk Model. This study was conducted according to the Strengthening the Reporting of Observational Studies in Epidemiology guideline for reporting case-control studies.

Results: By analysing the association between falls and the items included in the three tools, we identified significant fall-risk factors such as gait, dizziness or vertigo, changes in mental status, impulsivity, history of falling, elimination disorder, drugs affecting falls, and depression.

Conclusions: The Hendrich II fall-risk Model had the best predictive performance for falls of the three tools, considering the highest in the area under the curve and the Youden index that comprehensively analysed sensitivity and specificity, while the Johns Hopkins fall-risk Assessment Tool had the highest accuracy. The most significant fall-risk predictors are gait, dizziness or vertigo, change in mental state, and history of falling.

Relevance To Clinical Practice: To improve the fall assessment performance of the Morse Fall Scale at the study hospital, we propose that it be supplemented with four most significant fall-risk predictors identified in this study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jocn.15387DOI Listing
September 2020

Separation, Characterization, and Handling of Microalgae by Dielectrophoresis.

Microorganisms 2020 Apr 9;8(4). Epub 2020 Apr 9.

IHP-Leibniz-Institut für innovative Mikroelektronik, Im Technologiepark 25, 15236 Frankfurt (Oder), Germany.

Microalgae biotechnology has a high potential for sustainable bioproduction of diverse high-value biomolecules. Some of the main bottlenecks in cell-based bioproduction, and more specifically in microalgae-based bioproduction, are due to insufficient methods for rapid and efficient cell characterization, which contributes to having only a few industrially established microalgal species in commercial use. Dielectrophoresis-based microfluidic devices have been long established as promising tools for label-free handling, characterization, and separation of broad ranges of cells. The technique is based on differences in dielectric properties and sizes, which results in different degrees of cell movement under an applied inhomogeneous electrical field. The method has also earned interest for separating microalgae based on their intrinsic properties, since their dielectric properties may significantly change during bioproduction, in particular for lipid-producing species. Here, we provide a comprehensive review of dielectrophoresis-based microfluidic devices that are used for handling, characterization, and separation of microalgae. Additionally, we provide a perspective on related areas of research in cell-based bioproduction that can benefit from dielectrophoresis-based microdevices. This work provides key information that will be useful for microalgae researchers to decide whether dielectrophoresis and which method is most suitable for their particular application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/microorganisms8040540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232385PMC
April 2020

PRESCIENT: platform for the rapid evaluation of antibody success using integrated microfluidics enabled technology.

Lab Chip 2020 05 20;20(9):1628-1638. Epub 2020 Mar 20.

Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, USA.

Identifying antibodies (Abs) that neutralize infectious agents is the first step for developing therapeutics, vaccines, and diagnostic tools for these infectious agents. However, current approaches for identifying neutralizing Abs (nAbs) typically rely on dilution-based assays that are costly, inefficient, and only survey a small subset of the entire repertoire. There are also intrinsic biases in many steps of conventional nAb identification processes. More importantly, conventional assays rely on simple Ab-antigen binding assays, which may not result in identifying the most potent nAbs, as the strongest binder may not be the most potent nAb. Droplet microfluidic systems have the capability to overcome such limitations by conducting complex multi-step assays with high reliability, resolution, and throughput in a pico-liter volume water-in-oil emulsion droplet format. Here, we describe the development of PRESCIENT (Platform for the Rapid Evaluation of antibody SucCess using Integrated microfluidics ENabled Technology), a droplet microfluidic system that can enable high-throughput single-cell resolution identification of nAb repertoires elicited in response to viral infection. We demonstrate PRESCIENT's ability to identify Abs that neutralize a model viral agent, Murine coronavirus (murine hepatitis virus), which causes high mortality rates in experimentally infected mice. In-droplet infection of host cells by the virus was first demonstrated, followed by demonstration of in-droplet neutralization by nAbs produced from a single Ab-producing hybridoma cell. Finally, fluorescence intensity analyses of two populations of hybridoma cell lines (nAb-producing and non-nAb-producing hybridoma cell lines) successfully discriminated between the two populations. The presented strategy and platform have the potential to identify and investigate neutralizing activities against a broad range of potential infectious agents for which nAbs have yet to be discovered, significantly advancing the nAb identification process as well as reinvigorating the field of Ab discovery, characterization, and development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9lc01165jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269184PMC
May 2020

A comparison of coagulation test results from heparinized central venous catheter and venipuncture.

Blood Coagul Fibrinolysis 2020 Mar;31(2):145-151

Department of Hematology, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

: Blood sampling via heparin-locked central venous catheter, including coagulation tests, is possible in accordance with the Clinical & Laboratory Standards Institute guidelines. However, differences exist between the test values of samples obtained from central venous catheter and those obtained from peripheral veins, even the guidelines are followed. To compare the coagulation time between blood samples from the heparin-locked central venous catheter and peripheral veins. In total, 72 hospitalized patients using heparin-locked Hickman catheters were enrolled. Blood samples for coagulation testing were simultaneously obtained via the peripheral veins and heparin-locked Hickman catheters. For sampling from the catheters, 0.9% sodium chloride flushing was performed and 10 or 23 ml of blood was discarded prior to collecting the coagulation test samples. Correlation, Bland-Altman plot, covariate, and regression analysis were performed for data analyses. Despite following the guidelines, the activated partial thromboplastin time test values differed. In the 10 ml of blood discard group, a correlation coefficient of 0.378 and a mean bias of 6.46 s were determined, while and in the 23 ml blood discard group, a correlation coefficient of 0.80 and a mean bias of 2.518 s were determined. Therefore, the volume of blood discarded from the heparin-locked Hickman catheters may affect the activated partial thromboplastin time test values.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MBC.0000000000000890DOI Listing
March 2020

Enhancing droplet transition capabilities using sloped microfluidic channel geometry for stable droplet operation.

Biomed Microdevices 2020 01 21;22(1):15. Epub 2020 Jan 21.

Department of Biomedical Engineering, Texas A&M University, College Station, TX, 77843, USA.

Droplet-based microfluidics technology allows for the generation and control of droplets that function as independent chemical and biological reactors, enabling broad ranges of high-throughput assays. As more complex multi-step assays are being realized in droplet format, maintaining droplet stability throughout the assay becomes a critical requirement. Unfortunately, as droplets go through multiple manipulation steps, droplet breakage is commonly seen, especially where droplets have to go through sharp transitions in direction and shape. Standard microfabrication techniques typically result in inherent sharp geometry in Z-direction due to their two-dimensional fabrication nature. Recent advancement in micro- and nano- fabrication technology using two-photon polymerization (2PP) is enabling complex 3D microstructures with sub-micrometer resolution to be readily fabricated. Here, utilizing this microfabrication technique, we present a simple solution to the droplet stability challenge by utilizing sloped-geometry microfluidic channels to enable microdroplets to smoothly transition between microfluidic channels having two different heights without breakage. The technique and innovation demonstrated here have the potential to replace conventional droplet microfluidic device fabrication approaches and enable droplet microfluidic platforms to achieve significantly higher level of efficiency, accuracy, and stability never realized before.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10544-019-0466-xDOI Listing
January 2020

Digital quantification and selection of high-lipid-producing microalgae through a lateral dielectrophoresis-based microfluidic platform.

Lab Chip 2019 12 22;19(24):4128-4138. Epub 2019 Nov 22.

Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX 77843, USA. and Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, USA.

Microalgae are promising alternatives to petroleum as renewable biofuel sources, however not sufficiently economically competitive yet. Here, a label-free lateral dielectrophoresis-based microfluidic sorting platform that can digitally quantify and separate microalgae into six outlets based on the degree of their intracellular lipid content is presented. In this microfluidic system, the degree of cellular lateral displacement is inversely proportional to the intracellular lipid level, which was successfully demonstrated using Chlamydomonas reinhardtii cells. Using this functionality, a quick digital quantification of sub-populations that contain different intracellular lipid level in a given population was achieved. In addition, the degree of lateral displacement of microalgae could be readily controlled by simply changing the applied DEP voltage, where the level of gating in the intracellular lipid-based sorting decision could be easily adjusted. This allowed for selecting only a very small percentage of a given population that showed the highest degree of intracellular lipid content. In addition, this approach was utilized through an iterative selection process on natural and chemically mutated microalgal populations, successfully resulting in enrichment of high-lipid-accumulating microalgae. In summary, the developed platform can be exploited to quickly quantify microalgae lipid distribution in a given population in real-time and label-free, as well as to enrich a cell population with high-lipid-producing cells, or to select high-lipid-accumulating microalgal variants from a microalgal library.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9lc00850kDOI Listing
December 2019

Calreticulin is a Critical Cell Survival Factor in Malignant Neoplasms.

PLoS Biol 2019 09 30;17(9):e3000402. Epub 2019 Sep 30.

Sue and Bill Gross Stem Cell Research Center, Department of Molecular Biology and Biochemistry, University of California-Irvine, Irvine, California, United States of America.

Calreticulin (CRT) is a high-capacity Ca2+ protein whose expression is up-regulated during cellular transformation and is associated with disease progression in multiple types of malignancies. At the same time, CRT has been characterized as an important stress-response protein capable of inducing immunogenic cell death (ICD) when translocated to the cell surface. It remains unclear why CRT expression is preserved by malignant cells during the course of transformation despite its immunogenic properties. In this study, we identify a novel, critical function of CRT as a cell survival factor in multiple types of human solid-tissue malignancies. CRT knockdown activates p53, which mediates cell-death response independent of executioner caspase activity and accompanied full-length poly ADP ribose polymerase (PARP) cleavage. Mechanistically, we show that down-regulation of CRT results in mitochondrial Ca2+ overload and induction of mitochondria permeability transition pore (mPTP)-dependent cell death, which can be significantly rescued by the mPTP inhibitor, Cyclosporin A (CsA). The clinical importance of CRT expression was revealed in the analysis of the large cohort of cancer patients (N = 2,058) to demonstrate that high levels of CRT inversely correlates with patient survival. Our study identifies intracellular CRT as an important therapeutic target for tumors whose survival relies on its expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pbio.3000402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768457PMC
September 2019

Amnion membrane organ-on-chip: an innovative approach to study cellular interactions.

FASEB J 2019 08 4;33(8):8945-8960. Epub 2019 Jun 4.

Division of Maternal-Fetal Medicine and Perinatal Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, Texas, USA.

The amnion membrane that lines the human intrauterine cavity is composed of amnion epithelial cells (AECs) connected to an extracellular matrix containing amnion mesenchymal cells (AMCs) through a basement membrane. Cellular interactions and transitions are mechanisms that facilitate membrane remodeling to maintain its integrity. Dysregulation of cellular remodeling, primarily mediated by oxidative stress (OS), is often associated with preterm birth. However, the mechanisms that maintain membrane homeostasis remain unclear. To understand these mechanisms, we developed an amnion membrane organ-on-chip (AM-OOC) and tested the interactive and transition properties of primary human AECs and AMCs under normal and OS conditions. AM-OOC contained 2 chambers connected by type IV collagen-coated microchannels, allowing independent culture conditions that permitted cellular migration and interactions. Cells grown either independently or coculture were exposed to OS inducing cigarette smoke extract, antioxidant -acetyl-l-cysteine (NAC), or both. When grown independently, AECs transitioned to AMCs and migrated, whereas AMCs migrated without transition. OS caused AECs' transition but prevented migration, whereas AMCs' migration was unhindered. Coculture of cells facilitated transition, migration, and eventual integration in the contiguous population. OS cotreatment in both chambers facilitated AECs' transition, prevented migration, and increased inflammation, a process that was prevented by NAC. AM-OOC recapitulated cellular mechanisms observed and enabled experimental manipulation of cells to determine their roles during pregnancy and parturition.-Richardson, L., Jeong, S., Kim, S., Han, A., Menon, R. Amnion membrane organ-on-chip: an innovative approach to study cellular interactions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1096/fj.201900020RRDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662977PMC
August 2019

A continuous-flow acoustofluidic cytometer for single-cell mechanotyping.

Lab Chip 2019 01;19(3):387-393

Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, 100084, China.

The biophysical properties of cells such as their compressibility have been found to be closely related to disease progression such as cancer development and metastasis. As cancer cells are heterogeneous, rapid and high-throughput evaluation of cell biophysical properties at single-cell resolution is needed to assess their potential as biomarkers for cancer staging and prognosis. Acoustofluidics has shown promise as a contactless method for accurately measuring cell biophysical properties; however, previously reported methods had relatively low throughput due to their requirement of no-flow conditions. This work presents a high-throughput continuous flow-based acoustofluidic cell mechanotyping method at single-cell resolution that retains the advantage of simplicity and low-cost.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c8lc00711jDOI Listing
January 2019
-->