Microfluidic tissue biopsy and immune response drug evaluation devices and systems
Inventors
Beckwith, Ashley Lynne • Borenstein, Jeffrey • Moore, Nathan • Doty, Daniel • VELASQUEZ-GARCIA, Luis
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Assignees
Charles Stark Draper Laboratory Inc
Member
DraperDraper is an independent nonprofit engineering innovation company with a legacy spanning over 90 years, dedicated to delivering transformative solutions for national security, prosperity, and global challenges. Renowned for its pioneering work in guidance, navigation, and control (GN&C) systems, Draper partners with government, industry, and academia to engineer advanced technologies in space, defense, biotechnology, and electronic systems. The company leverages multidisciplinary expertise, digital engineering, and a collaborative approach to provide field-ready prototypes, mission-critical systems, and innovative research. Draper’s mission is to ensure the nation's security and prosperity by delivering sustainable, cutting-edge solutions that address the toughest problems of today and tomorrow, while fostering an inclusive and diverse workforce. Draper also invests in the next generation of innovators through robust educational programs, including internships, co-ops, and the Draper Scholars Program, integrating academic research with real-world problem-solving.
Draper is an independent nonprofit engineering innovation company with a legacy spanning over 90 years, dedicated to delivering transformative solutions for national security, prosperity, and global challenges. Renowned for its pioneering work in guidance, navigation, and control (GN&C) systems, Draper partners with government, industry, and academia to engineer advanced technologies in space, defense, biotechnology, and electronic systems. The company leverages multidisciplinary expertise, digital engineering, and a collaborative approach to provide field-ready prototypes, mission-critical systems, and innovative research. Draper’s mission is to ensure the nation's security and prosperity by delivering sustainable, cutting-edge solutions that address the toughest problems of today and tomorrow, while fostering an inclusive and diverse workforce. Draper also invests in the next generation of innovators through robust educational programs, including internships, co-ops, and the Draper Scholars Program, integrating academic research with real-world problem-solving.
Publication Number
US-11852626-B2
Publication Date
2023-12-26
Expiration Date
Abstract
This disclosure describes microfluidic tissue biopsy and immune response drug evaluation devices and systems. A microfluidic device can include an inlet channel having a first end configured to receive a fluid sample optionally containing a tissue sample. The microfluidic device can also include a tissue trapping region at the second end of the inlet channel downstream from the first end. The tissue trapping region can include one or more tissue traps configured to catch a tissue sample flowing through the inlet channel such that the fluid sample contacts the tissue trap. The microfluidic device can also include one or more channels providing an outlet.
Core Innovation
This disclosure describes a microfluidic device comprising a substrate defining an inlet channel having a first end configured to receive a fluid sample optionally containing a tissue sample, a tissue trapping region at a second end of the inlet channel downstream from the first end, the tissue trapping region including one or more tissue traps configured to catch the tissue sample flowing through the inlet channel such that the fluid sample contacts the tissue trapping region, and one or more channels providing an outlet. The devices can include a bubble trapping structure coupled to the inlet channel downstream from the inlet port and an optical interface providing optical access to the tissue sample positioned within the tissue trapping region. The disclosure describes specific tissue trap designs including a heart-shaped branching structure, ribbed channel bottom structure, S-curve (circuitous) structure, and suction port structure that serve to control and freeze the position of a tissue biopsy sample in a flow stream.
The background states that current technology for simulating dynamic processes involving interactions between mammalian tissue samples and cells is gated by the inability to recapitulate the tissue microenvironment and interactions between tissues, therapeutic compounds and the host immune system. This disclosure aims to establish a robust platform to recapitulate the tissue microenvironment and interactions with host immune cells and to permit real-time observation of tumor viability and responses to therapeutic compounds while permitting control over perfusion rates and shear forces. The disclosure further describes integration of the device with systems capable of sustaining the tissue, maintaining control over flow rate, viability of cells and density of circulating components, and avoiding problems common to microfluidic systems such as bubbles, debris, blockages or variability in flow rates; [procedural detail omitted for safety].
Claims Coverage
Identifies three main inventive features corresponding to the independent claims of the patent.
Suction channels configured to hold tissue in place
one or more channels providing an outlet and comprising one or more suction channels downstream of the one or more tissue traps and configured to hold the tissue sample in place within the one or more tissue traps.
Ribbed channel tissue trapping region
the tissue trapping region comprises a ribbed channel coupling the inlet channel to the one or more channels providing the outlet.
Circuitous channel with tissue trap at center of curved portion
the tissue trapping region comprising a circuitous channel having a first curved portion coupled to the second end of the inlet channel, wherein at least one of the one or more tissue traps is positioned at a center of the first curved portion such that the fluid sample flows along the first curved portion past the tissue trapping region.
Independent claims disclose (1) outlet channels comprising suction channels to hold tissue in place, (2) a ribbed-channel tissue trapping region coupling inlet to outlet, and (3) a circuitous-channel tissue trapping region with tissue traps positioned at centers of curved portions to present flow past trapped tissue.
Stated Advantages
Recapitulate the tissue microenvironment and interactions with host immune cells.
Permit real-time observation of tumor viability and responses to therapeutic compounds.
Provide control over perfusion rates and shear forces to ensure relevance to human in vivo conditions.
Integrate features to sustain tissue and maintain control over flow rate, cell viability, and density of circulating components while avoiding bubbles, debris, blockages, and variability in flow rates.
Reduce the number of required connections and overall fluid volume by incorporating an in-line bubble trapping structure into the microfluidic device.
Optimize the cross-section of interaction between circulating fluid components and tissue biopsy samples.
Documented Applications
Simulate interactions between tumors or other tissue samples and the immune system.
Provide a microenvironment for testing the effectiveness of immunotherapy treatments on lymphocytes and tumor biopsies taken directly from a patient.
Ex vivo simulation of the dynamics of tissue interactions with various fluid components, such as cells, medications, or therapeutic compounds.
Permit observation and control over interactions between fluid components and excised tissues such as tumor biopsy samples, skin biopsies, and epithelial tissues including gut, airway, renal or reproductive tract tissues.
Integrate with systems that include resistance channels, fluidic connectors and branch points, tissue sample loading ports, bubble trapping structures, drug dosing and media sampling ports, cell containment vessels, and manifolds for distribution of cells and gas pressure lines.
Serve as an optical interface that can be examined by a microscope or camera positioned in proximity to the tissue trapping region.
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