Studying the Response of Aortic Endothelial Cells under Pulsatile Flow Using a Compact Microfluidic System

Mohammed, Mokhaled Mustafa; Thurgood, Peter; Gilliam, Christopher; Nguyen, Ngan; Pirogova, Elena; Peter, Karlheinz; Khoshmanesh, Khashayar; Baratchi, Sara

doi:10.1021/acs.analchem.9b03247

Cited by 45 publications

(34 citation statements)

References 61 publications

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“…Pulsatile flow also increased cell size and changed the distribution of the endothelial cell adhesion molecule CD31 and mechanical sensor PIEZO1, suggesting that EC structure is affected by pulsatile flow. Pulsation, including frequency and amplitude, plays an important role in EC protein expression and morphology 7,8 . Disturbed flow is known to affect EC behavior, including EC turnover, low density lipoprotein permeability, atherogenesis, and gene expression [40][41][42][43] .…”

Section: Endothelial Cells Differentiated Under Lqts Pulsatile Flow Ementioning

confidence: 99%

“…Endothelial cells (ECs) line the lumen of blood vessels, so pulsatile flow provides a more relevant in vivo microenvironment for these ECs compared to constant flow. Numerous studies have shown that pulsatile flow and constant flow have different effects on ECs in vitro, including EC morphology and alignment 7,8 , gene expression 9, 10 , distribution of adhesion proteins 8 , cell proliferation, and apoptosis 11 . The pulsation frequency and peak amplitude of the pulsatile flow also plays an important role in EC morphology and protein expression 7,8 .…”

Section: Introductionmentioning

confidence: 99%

“…Numerous studies have shown that pulsatile flow and constant flow have different effects on ECs in vitro, including EC morphology and alignment 7,8 , gene expression 9, 10 , distribution of adhesion proteins 8 , cell proliferation, and apoptosis 11 . The pulsation frequency and peak amplitude of the pulsatile flow also plays an important role in EC morphology and protein expression 7,8 . Additionally, fluidic shear stress significantly affects differentiation efficiency and related gene expression during the differentiation process 12,13 , but the effects of pulsatile shear stress have not been well characterized.…”

Section: Introductionmentioning

confidence: 99%

“…Previous methods to study EC behavior in vitro have generated pulsatile shear stress using pneumatic or piezoelectric pressure pumps and simulated waveforms 8,18,19 . However, the underlying pump technologies of these previous approaches lack the temporal resolution to recapitulate the frequency content of the time-dependent flow generated by heart contractions.…”

Section: Introductionmentioning

confidence: 99%

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Adaptable pulsatile flow generated by quantitative imaging of stem-cell derived cardiomyocytes for disease modeling

Qian

Gil

Guzman

et al. 2020

Preprint

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Endothelial cells (EC) in vivo are continuously exposed to a mechanical microenvironment from blood flow, and fluidic shear stress plays an important role in EC behavior. New approaches to generate physiologically and pathologically relevant pulsatile flows are needed to understand EC behavior under different shear stress regimes. Here, we demonstrate an adaptable pump (Adapt-Pump) platform for generating pulsatile flows via quantitative imaging of human pluripotent stem cell-derived cardiac spheroids (CS). Pulsatile flows generated from the Adapt-Pump system can recapitulate unique CS contraction characteristics, accurately model responses to clinically relevant drugs, and simulate CS contraction changes in response to fluidic mechanical stimulation. We discovered that ECs differentiated under a long QT syndrome derived pathological pulsatile flow exhibit abnormal EC monolayer organization. This Adapt-Pump platform provides a powerful tool for modeling the cardiovascular system and improving our understanding of EC behavior under different mechanical microenvironments.

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Section: Endothelial Cells Differentiated Under Lqts Pulsatile Flow Ementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Adaptable pulsatile flow generated by quantitative imaging of stem-cell derived cardiomyocytes for disease modeling

Qian

Gil

Guzman

et al. 2020

Preprint

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“…pumps 22,23 . Syringe pumps, in particular, are among the most common type of pump used for laboratory microfluidics.…”

mentioning

confidence: 99%

Open-source, 3D-printed Peristaltic Pumps for Small Volume Point-of-Care Liquid Handling

Behrens

Fuller

Swist

et al. 2020

Sci Rep

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Microfluidic technologies are frequently employed as point-of-care diagnostic tools for improving time-to-diagnosis and improving patient outcomes in clinical settings. These microfluidic devices often are designed to operate with peripheral equipment for liquid handling that increases the cost and complexity of these systems and reduces their potential for widespread adoption in low resource healthcare applications. Here, we present a low-cost (~$120), open-source peristaltic pump constructed with a combination of three dimensional (3D)-printed parts and common hardware, which is amenable to deployment with microfluidic devices for point-of-care diagnostics. This pump accepts commonly available silicone rubber tubing in a range of sizes from 1.5 to 3 mm, and is capable of producing flow rates up to 1.6 mL min −1 . This device is programmed with an Arduino microcontroller, allowing for custom flow profiles to fit a wide range of low volume liquid handling applications including precision liquid aliquoting, flow control within microfluidics, and generation of physiologically relevant forces for studying cellular mechanobiology within microfluidic systems.Microfluidic systems are ubiquitous tools within science and engineering laboratories around the world that enable low-cost and high throughput analysis via the miniaturization and parallelization of experimental systems. To enable broader applications and lower the barrier to entry for using microfluidic technology, developing open-source and low-cost tools for handling fluids is a promising avenue of research 1-3 . Open-source microfluidic tools could be particularly impactful when used for point-of-care diagnostics in resource limited settings. The growing use of microfluidics in point-of-care diagnostic roles is driven by the desire for more personalized medical treatments that are tailored to the specific pathologies identified in the patient 4-7 . This is because assays that can be performed at the point of care dramatically improve time-to-diagnosis, leading to improvements in medical practitioner decision making and patient outcomes 8 . In order for point-of-care diagnostic devices to be widely adopted into more clinical settings so that they can effectively improve healthcare outcomes, advances must be made in key enabling technologies, including improved microfluidic device designs, and improved peripheral systems for fluid actuation and sensing 9 . Increasing the use of open-source tools for future point-of-care diagnostic tools would enable reductions in system cost, and increase ease of use.Microfluidic point-of-care diagnostic systems must include three basic components: the physical microfluidic device, systems to read the assay output, and systems to control the flow of liquid reagents (Fig. 1A). The physical microfluidic device can be manufactured from a wide range of low-cost materials, including PDMS 10

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A Highly Programmable Magnetic Micropump

Peng

Guo

2021

Adv Materials Technologies

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A cheap, small, convenient, reliable, and durable lab‐on‐a‐chip is needed for various scenarios in practical applications. The authors hope to use the chip only after plugging in a mobile phone. An ideal micropump design is obtained by simplifying the micropump theory, reducing the micropump to 1 mm (oscillator pump, O‐pump), the external device (actuator) to 5 mm, and the power to 10 mW. This system costs ≈$10 and can work in harsh fluid environments (such as animal cell culture) for an extended period (a few months of testing). An MP3 player drives two O‐pumps by a programmable playlist. The O‐pump is a permanent magnet positive sphere in an open fluid space, which is not easy to block and rolls freely without wear. Only controlled by the magnetic field, the O‐pump avoids interference from the current, electric field, and chemical activity. The fluid is driven by a vibrating motion, in open or sealed channels, with no unique materials and no other equipment. The debris, bubbles, and fibers in the blood viscosity fluid do not affect the pump's function. The system can be applied in different scenarios, such as the automatic cultivation of stem cells or point‐of‐care devices.

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Studying the Response of Aortic Endothelial Cells under Pulsatile Flow Using a Compact Microfluidic System

Cited by 45 publications

References 61 publications

Adaptable pulsatile flow generated by quantitative imaging of stem-cell derived cardiomyocytes for disease modeling

Adaptable pulsatile flow generated by quantitative imaging of stem-cell derived cardiomyocytes for disease modeling

Open-source, 3D-printed Peristaltic Pumps for Small Volume Point-of-Care Liquid Handling

A Highly Programmable Magnetic Micropump

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