Microfluidic assay in idealized microvascular network for characterization of leukocyte adhesion cascade
Inventors
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-8940494-B2
Publication Date
2015-01-27
Expiration Date
Abstract
Methods of assaying the leukocyte adhesion cascade (LAC) and monitoring leukocyte rolling, adhesion, and/or migration can be implemented with an apparatus that includes an idealized microvascular network (IMN) of one or more interconnected idealized flow channels in fluid communication through a porous wall with a tissue space (e.g., idealized tissue space). The methods of assaying the LAC can be implemented with means for quantifying modulation of the leukocyte adhesion cascade. Methods of assaying the LAC can be implemented with the device and one or more active agents to monitor leukocyte rolling, adhesion, and/or migration in the presence of absence of the active agent. Migration can be through the idealized flow channels, through the porous wall, and/or into the tissue space.
Core Innovation
Methods of assaying the leukocyte adhesion cascade and monitoring leukocyte rolling, adhesion, and/or migration are implemented with an apparatus that includes an idealized microvascular network (IMN) of one or more interconnected idealized flow channels in fluid communication through a porous wall with a tissue space. The methods are implemented with an optically transparent microfluidic chip comprising one or more idealized flow channels having inlets and outlets and one or more tissue spaces bordering and fluidly coupled with the one or more idealized flow channels, and include means for quantifying modulation of the leukocyte adhesion cascade.
The invention addresses a need in the art for an assay capable of identifying and screening for agents affecting the leukocyte adhesion cascade encompassing rolling, adhesion, and migration because flow chambers cannot model transmigration, transwell and Boyden chambers do not account for fluid shear or provide real-time visualization of migration, and no experimental model currently resolves rolling, adhesion and migration in a single in vitro assay.
Claims Coverage
Independent claims identified: four. Main inventive features are extracted from each independent claim and summarized below.
Optically transparent microfluidic chip comprising idealized flow channels and tissue spaces
An optically transparent microfluidic chip comprising one or more idealized flow channels having one or more inlets and one or more outlets and one or more tissue spaces bordering and fluidly coupled with the one or more idealized flow channels, wherein the one or more idealized flow channels surround the one or more tissue spaces.
Porous wall coupling with defined apertures
A first wall separating a first idealized flow channel from a first tissue space includes a plurality of apertures that fluidly couple the first idealized flow channel with the first tissue space, the plurality of apertures having a third cross-sectional dimension (claimed ranges include 0.2 micron to 30 microns and related subranges).
Assay workflow for assessing modulation of leukocyte behavior
A method comprising introducing leukocytes into the one or more idealized flow channels, flowing a solution containing one or more agents through the one or more idealized flow channels before, during, or after introduction of leukocytes, locating and counting leukocytes in the microfluidic chip, and based upon the locations and numbers of leukocytes, determining whether the one or more agents modulate leukocyte rolling, adhesion, and/or migration.
Variations in device geometry and surface state
Alternate claimed embodiments include IMN channels that define a perimeter of tissue spaces, IMN and tissue spaces that are planar, and IMN luminal surfaces coated with a first cell type with the tissue spaces either devoid of cells or including a different second cell type.
The independent claims disclose (a) an optically transparent microfluidic chip architecture with idealized flow channels and adjoining tissue spaces coupled by apertures, (b) specified aperture and channel cross-sectional dimension ranges, (c) a method of introducing leukocytes and agents and quantifying modulation by locating and counting leukocytes, and (d) device variations including planar layouts and luminal surface cell coatings.
Stated Advantages
Resolves and facilitates direct assessment of individual steps in the leukocyte adhesion cascade including rolling, firm arrest (adhesion), spreading, and extravasation into the extra-vascular tissue space.
Provides a rapid assay for anti-inflammatory markers and drugs targeted to affect the leukocyte adhesion cascade.
Enables quantitative end point measurement, real-time visualization of cell migration, and automation of assay method steps.
Permits assessment of particle and drug delivery behavior and measurement of properties such as circulation, stability, half-life, aggregation, and degradation in a microvascular context.
Documented Applications
Identifying and screening for agents that modulate leukocyte rolling, adhesion, and migration, including anti-inflammatory markers and drugs.
Assaying drug delivery vehicles and quantifying the amount of a drug delivery vehicle and/or drug reaching tissue spaces and interacting with leukocytes or other cells.
Real-time visualization and quantitative measurement of leukocyte rolling, adhesion, and migration under controlled shear conditions and varied microvascular geometries.
Growing three-dimensional tissues (e.g., tumors) in tissue spaces for assays, including use of tumor cells obtained from a patient and cultured in the tissue space of the device.
Applying the device and methods to study particle transport, particle adhesion, blood-brain barrier diffusion and delivery, and related drug delivery and barrier-mimicking assays as described in the incorporated references.
Interested in licensing this patent?