Design and Fabrication of Pulmonary Arterial Hypertension on a Chip Microfluidics System

Lead Research Organisation: Imperial College London
Department Name: Dept of Chemistry

Abstract

Design and fabrication of Pulmonary Arterial Hypertension on a chip microfluidics system with an inbuilt pressure sensor array to reproduce and monitor in vivo mechanical stimuli on cultured cells.

One of the greatest challenges associated with developing artificial pulmonary arteries to better understand disease (e.g. pulmonary arterial hypertension) or disease progression is to ensure that the artificial platforms mimic as closely as possible the true environment. This includes ensuring that adequate measures have been taken to determine the biophysical conditions of pulmonary arterioles. For example, the development of patient specific pulmonary vascular tree computational models to determine the wall shear stress, circumferential and radial strains that vascular cells experience in healthy and diseased states. The material and geometric properties of Artery-on-a-Chip channel walls differ largely from in-vivo arteries. Thus, the design of novel microfluidic platforms to reproduce these stresses and strains in-vitro, whilst incorporating sensors to monitor them in real-time is required. This challenge is compounded by the fact that cultured cells can only survive if the materials used are sufficiently gas permeable and exhibit a similar surface tension to real systems. Scientific goals: (1) To develop computational models to accurately obtain the forces acting on pulmonary arteriole vascular wall cells. (2) Design and develop novel microfluidic platforms to reproduce these forces on cultured cells. (3) Incorporate sensors to monitor biophysical conditions in real-time whilst maintaining biocompatibility.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509486/1 01/10/2016 31/03/2022
1970404 Studentship EP/N509486/1 01/10/2017 31/01/2021 Timothy Jason Smith
 
Description 1) A model of the entire Pulmonary vascular tree has been created that incorporates geometry obtained from CT images allowing patient specific models to be obtained. This model allows for the stresses, strains and pressures acting on the vascular cells in arterioles to be obtained.
2) COMSOL FSI simulations verified that previous assumptions about the pressure field within a co-culture artery on a chip device were invalid, which discredits any quantitative claims and conclusions of those studies.
3) A 3d FSI model of a coculture artery on a chip PDMS device was created in COMSOL v4.4. A numerical equation based on Christov et al.'s work was fitted allowing for the pressure field within the artery on a chip to be predicted from the volumetric flow rate at the inlet, and outlet pressure.
4) A passive microfluidic circuit has been designed that can obtain sinusoidal flow from gravity head pressure and phase shift the sinusoids forming a flow rate wave generator protoype.
5) COMSOL 3d FSI models of hydraulic capacitors, diodes, transistors and resistors were created to determine the effect of geometry and microfluidic conditions on each of the components' functionality, and validate analytical formulas in literature.
6) Pressure sensor side channels were integrated onto the bottom layer of the artery on a chip design to allow for real-time pressure field measurement within the chip.
Exploitation Route The computational model can be built upon by improving the vascular wall constitutive model from linearly elastic to both hyperelastic and viscoelastic models.
Moreover, the robust vessel on a chip design methodology outlined in this project can act as the new gold standard for replicating physiological conditions within the culturing device.

The passive flow rate wave generator circuit can be built upon by refining the phase shift element to allow for low cost flow rate control for numerous microfluidic applications.

Integrated pressure sensors within the artery on a chip device can be used to allow internal measurement of the pressure variation within a microchannel, further research into minimizing the size of these pressure sensors and possible flow reversal experiment applications.
Sectors Digital/Communication/Information Technologies (including Software),Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology,Other