Synthetic microfluidic microvasculature network
Inventors
Prabhakarpandian, Balabhaskar • Sundaram, Shivshankar • Pant, Kapil
Assignees
Publication Number
US-8175814-B2
Publication Date
2012-05-08
Expiration Date
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Abstract
A synthetic microfluidic microvasculature network and associated methods mimic the structure, fluid flow characteristics, and physiological behavior of physiological microvasculature networks. Computational methods for simulating flow and particle adherence in synthetic and physiological microvascular systems and methods for determining parameters influencing particle adhesion and drug delivery are described with applications in the optimization of drug delivery and microvascular treatments and in describing disease mechanisms that affect the microvasculature.
Core Innovation
The present invention provides synthetic microfluidic microvasculature networks (SMNs) and associated methods that mimic the structure, fluid flow characteristics, and physiological behavior of physiological microvasculature networks. Computational methods for simulating flow and particle adherence in synthetic and physiological microvascular systems and methods for determining parameters influencing particle adhesion and drug delivery are described with applications in the optimization of drug delivery and microvascular treatments and in describing disease mechanisms that affect the microvasculature.
The invention addresses the need for an in-vitro flow chamber that accurately simulates the anatomical and hemodynamic properties of physiological microvascular networks and for methods of using such a flow chamber to describe and predict the behavior of particles and cells in microvascular networks. The invention provides microfluidic chips comprising SMNs with flow channels that possess key geometric and topological features causing them to display the same types of fluid flow patterns and particle adhesion patterns as are found in physiological microvascular networks and further provides reduced reagent requirements and the ability to develop plastic, disposable chips to eliminate concerns of cross-contamination.
Claims Coverage
Two independent claims are present (claims 1 and 8). Claim 1 discloses four main inventive features and claim 8 discloses five main inventive features.
Synthetic microvascular network with non-linear interconnected flow channels
Providing a synthetic microvascular network comprising a plurality of non-linear interconnected flow channels that form geometrical features and have fluid flow properties found in physiological microvascular networks.
Particle perfusion and identification in SMN
Introducing a sample comprising a liquid suspension of particles into an inlet of the synthetic microvascular network, causing the sample to flow through the synthetic microvascular network, and identifying the locations, numbers, and/or distribution of particles that deposit in the synthetic microvascular network.
Correlation of deposition with adhesion parameter
Correlating the locations, numbers, and/or distribution of particles identified with the parameter that influences particle adhesion in the microvascular network.
Defined geometric characteristics of flow channels
The plurality of non-linear, interconnected flow channels possess a geometric characteristic selected from the group consisting of a variable cross-sectional shape, a variable cross-sectional area, a turn, a bend, a bifurcation, a junction, a convolution, an anastamosis, and combinations thereof.
Selection of drug or substrate property
Selecting at least one physical, chemical, and/or biological property of the drug or a substrate to which the drug may be attached.
Drug/substrate perfusion in SMN
Introducing a sample comprising a liquid suspension of drug or substrate to which the drug may be attached into an inlet of the synthetic microvascular network, causing the suspension to flow through the synthetic microvascular network, and identifying the locations, numbers, and/or distribution of drug or substrate to which the drug may be attached that deposit in the synthetic microvascular network.
Correlation of drug deposition with selected properties
Correlating the locations, numbers, and/or distribution of drug that deposit in the synthetic microvascular network with the at least one physical, chemical, and/or biological property of the drug or substrate to which the drug may be attached.
Use of averaged microvascular network
Providing that the synthetic microvascular network can be an averaged microvascular network or have a geometry that corresponds to at least a portion of a physiological microvascular network.
Drug delivered in particulate or carrier form
The method contemplates that the drug can be in the form of a particle and that the substrate to which the drug may be attached can be a liposome, a lipoprotein, a polymer carrier particle, a carrier molecule, or a targeting molecule.
The independent claims cover methods that employ anatomically and hemodynamically realistic SMNs with specified geometric features to perfuse particles or drug-containing suspensions, identify deposited particle/drug locations and distributions, and correlate those deposition patterns with adhesion or delivery-influencing parameters and selected drug/substrate properties.
Stated Advantages
Mimics the structure, fluid flow characteristics, and physiological behavior of physiological microvasculature networks.
Requires quantities of reagents that are reduced by orders of magnitude compared with currently used techniques.
Allows development of plastic, disposable chips eliminating concerns of cross-contamination.
Reproduces fluid flow and particle adhesion patterns observed in physiological microvascular networks.
Provides computational (CFD-based) models capable of analyzing fluid flow and particle deposition/adhesion to extract predictive relationships and assist design of experiments and treatment protocols.
Documented Applications
Optimization of drug delivery and microvascular treatments.
Describing disease mechanisms that affect the microvasculature such as inflammation, diabetes and hypertension.
An anatomically realistic, in-vitro/in-silico toolkit to study microvascular processes such as leukocyte adhesion, platelet adhesion, inflammation, chemotaxis, thrombosis, vascular activation, and the effects of shear rate on vascular endothelial cells.
A microfluidic chip for in-vitro optimization of vehicles for targeted drug delivery.
Generation of SMNs comprising patterns of channels obtained from one image or a combination of images of in-vivo microvascular networks, and averaged microvascular networks derived from multiple physiological networks.
SMNs that mimic physiological microvascular networks and comprise cells attached and/or cultured on the inner surfaces of flow channels and substrates coated on inner surfaces to facilitate adhesion.
Screening libraries of microencapsulated drugs and cancer targeting molecules using SMNs coated with target tumor cells and/or corresponding virtual SMNs; co-culture of tumor cells with endothelial cells.
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