Synthetic microfluidic blood-brain barrier
Inventors
Prabhakarpandian, Balabhaskar • Pant, Kapil • Sundaram, Shivshankar • Bhatt, Ketan Harendrakumar
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Assignees
MemberSynVivoSynVivoSynVivo is a pioneering provider of cell-based microfluidic organ-on-chip platforms, delivering biologically realistic microenvironments for real-time study of cellular behavior, drug delivery, and drug discovery. Their proprietary technology bridges microfluidics and bioengineering, enabling advanced research in life sciences, disease modeling, and personalized medicine. SynVivo's chips support microvascular networks that closely mimic in vivo tissue conditions, validated by scientific research to more accurately reflect human biology than conventional culture methods. The platform is especially impactful for personalized cancer therapy, allowing patient-derived cells to be used for drug efficacy testing in a simulated tumor environment. SynVivo also distributes a wide range of high-quality primary cells and cell lines from various species, supporting research in immunology, cardiovascular, and cancer biology.
SynVivo is a pioneering provider of cell-based microfluidic organ-on-chip platforms, delivering biologically realistic microenvironments for real-time study of cellular behavior, drug delivery, and drug discovery. Their proprietary technology bridges microfluidics and bioengineering, enabling advanced research in life sciences, disease modeling, and personalized medicine. SynVivo's chips support microvascular networks that closely mimic in vivo tissue conditions, validated by scientific research to more accurately reflect human biology than conventional culture methods. The platform is especially impactful for personalized cancer therapy, allowing patient-derived cells to be used for drug efficacy testing in a simulated tumor environment. SynVivo also distributes a wide range of high-quality primary cells and cell lines from various species, supporting research in immunology, cardiovascular, and cancer biology.
Publication Number
US-8417465-B2
Publication Date
2013-04-09
Expiration Date
Abstract
An apparatus and method for assaying blood-brain barrier properties for drug and drug delivery vehicle screening comprising of a microfluidic apparatus with gaps separating lumen and tissue space enabling formation of tight junctions similar to in vivo conditions using endothelial cells and brain cells.
Core Innovation
Screening drug candidates and drug delivery vehicles for their abilities to cross from the blood into the brain through the Blood-Brain Barrier (BBB) is an important aspect of the development of Central Nervous System (CNS) therapeutics. Available in vitro BBB assays use incubation chambers separated by a filter membrane designed to mimic the BBB. Such devices do not reproduce physiological microenvironmental parameters, shear stress induced by blood flow and transport effects caused by phenotypic changes in the microvasculature. In vivo BBB assays involve small animal models that are expensive, lengthy and difficult to scale up for high throughput screening.
The Synthetic Microvascular Blood-Brain Barrier (SyM-BBB) comprises a plastic, disposable and optically clear microfluidic chip with embedded microfluidic flow channels having geometric features and sizes similar to those found in vivo. The device comprises two sides/chambers: (1) an apical side/chamber in which endothelial cells (primary or immortalized) are grown, and (2) a basolateral side/chamber in which neuronal, glial and astrocytes (primary or immortalized) are grown or media conditioned with one or combination of the cells is located. Fluid within channels on the apical side is in liquid communication with one or more basolateral side tissue spaces via 0.2-5 μm gaps in the walls comprising repetitive, isolated structures or “islands,” preferably embodied as posts or pillars.
The integrity and tightness of SyM-BBB can be probed either fluidically using permeability assays or electrically by measuring resistivity or complex impedance across the channel walls. For permeability studies, tagged (e.g., fluorescently labeled) drug and/or drug delivery vehicle candidates are introduced into an apical side of the SyM-BBB and the movement of candidates from the flow channels through the layer(s) of cells and into the tissue space(s) is measured using one or more standard imaging techniques. The measured permeabilities of candidates may be used to objectively compare drugs in their ability to cross the BBB. Following an insult, inflammatory responses and interactions of cells (leukocytes, neurons, etc.) can be analyzed and screening of therapeutics (e.g., drugs, stem cells) for restoration of normal conditions is also possible.
Claims Coverage
Two independent claims were identified. Four main inventive features were extracted from the independent claims.
Microfluidic chip comprising interconnected flow channels and a tissue space
a network of interconnected flow channels in liquid communication with a network inlet and a network outlet, said flow channels having luminal cross-sectional dimensions of between 10 μm and 500 μm and a tissue space in liquid communication with a tissue space inlet and a tissue space outlet, said tissue space having cross-sectional luminal dimensions of between 100 μm and 1 cm wherein: the tissue space is separated from a lumen of at least one flow channel by a liquid permeable wall and is in liquid communication with the at least one flow channel through said liquid permeable wall;
Luminal surfaces with endothelial cells and tissue space with brain cells or media
the luminal surfaces of the flow channels are coated with endothelial cells; and the luminal surfaces of the tissue space contains brain cells and/or cell growth media;
Method steps of introducing, moving and quantifying drug delivery
introducing a liquid containing the drug or drug delivery vehicle into a network inlet of an optically transparent plastic microfluidic chip; causing the liquid containing the drug or drug delivery vehicle to move though the network of interconnected flow channels; and quantifying the amount of the drug or drug delivery vehicle reaching the tissue space.
Optically transparent microfluidic chip as a claimed apparatus
An optically transparent microfluidic chip comprising: a network of interconnected flow channels in liquid communication with a network inlet and a network outlet, said flow channels having luminal cross-sectional dimensions of between 10 μm and 500 μm and a tissue space in liquid communication with a tissue space inlet and a tissue space outlet, said tissue space having cross-sectional luminal dimensions of between 100 μm and 1 cm wherein: the tissue space is separated from a lumen of at least one flow channel by a liquid permeable wall and is in liquid communication with said flow channel through said liquid permeable wall; the luminal surfaces of the flow channels are coated with endothelial cells; and the luminal surfaces of the tissue space contains brain cells and/or cell growth media.
The independent claims cover (1) a method that introduces and moves a liquid containing a drug or drug delivery vehicle through an optically transparent microfluidic chip having interconnected flow channels and a tissue space separated by a liquid permeable wall, with endothelial cells on flow channel surfaces and brain cells or growth media in the tissue space, and (2) an optically transparent microfluidic chip having the same structural elements and cell arrangements.
Stated Advantages
Accurately reproduces in vivo size and flow microenvironments and enables a physiologically-relevant testing system for drug screening and delivery experiments.
Provides cost- and time-effective formats for real-time visualization or quantitation of the transport of drug and drug delivery candidates across the BBB.
Uses inexpensive, disposable polymeric microfluidic chips that can realize long-term cell culture and cellular assays.
May be readily extended onto standard 24 or 96 well plates, providing a ready method to scale up to high-throughput screening.
Enables study of dysfunction of the BBB following an insult and visualization and quantitation of interactions of cells under normal and pathological conditions.
Documented Applications
Assaying blood-brain barrier properties for drug and drug delivery vehicle screening and predicting drug and drug carrier transport across the BBB.
Studying dysfunction of the BBB following an insult (biological, chemical, mechanical or electrical) and analyzing inflammatory responses and interactions of cells.
Screening of therapeutics (e.g., drugs, stem cells) for restoration of normal conditions.
Measuring integrity and tightness of the BBB using permeability assays or electrical measurements such as resistivity or complex impedance.
Comparing permeabilities of candidate drugs and drug delivery vehicles using tagged (e.g., fluorescently labeled) compounds and standard imaging techniques.
Scaling up to high-throughput screening by realizing the microchip format compatible with standard 24 or 96 well plates.
Interested in licensing this patent?