Systems and methods for fabricating microfluidic devices
Inventors
Beckwith, Ashley Lynne • Borenstein, Jeffrey • Moore, Nathan • Doty, Daniel • Velásquez-García, Luis
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Assignees
Charles Stark Draper Laboratory Inc • Massachusetts Institute of Technology
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-12208385-B2
Publication Date
2025-01-28
Expiration Date
Abstract
This disclosure describes techniques for fabricating a high-resolution, non-cytotoxic and transparent microfluidic device. A material can be selected based on having an optical property with a predetermined degree of transparency to provide viewability of a biological sample through the microfluidic device and a level of cytotoxicity within a predetermined threshold to provide viability of the biological sample within the microfluidic device. An additive manufacturing technique can be selected from a plurality of additive manufacturing techniques for fabricating the microfluidic device based on the selected material to provide a resolution of dimensions of one or more channels of the microfluidic device higher than a predetermined resolution threshold.
Core Innovation
This disclosure describes techniques for fabricating a high-resolution, non-cytotoxic and transparent microfluidic device by selecting a material based on having an optical property with a predetermined degree of transparency to provide viewability of a biological sample through the microfluidic device and a level of cytotoxicity within a predetermined threshold to provide viability of the biological sample within the microfluidic device, and by selecting an additive manufacturing technique from a plurality of additive manufacturing techniques for fabricating the microfluidic device based on the selected material to provide a resolution of dimensions of one or more channels of the microfluidic device higher than a predetermined resolution threshold. Solid freeform fabrication processes, such as 3D printing, are used to produce devices capable of ex vivo simulation of the dynamics of cell-tissue interactions and to monolithically integrate various features including tissue capture regions, cell flow channels, resistance lines and fluidic connections, and bubble traps.
The background identifies limitations of conventional microfluidic fabrication, including PDMS hydrophobicity and adsorption, assembly complexity of multi-wafer stacks, laborious alignment and bonding processes, limited geometries, and low fabrication yield. The systems and methods provide materials and methods to make biocompatible microfluidic devices having high degree of transparency to visible light, features with high resolution (less than 100, 150, 200 or 250 microns), and low to no autofluorescence, simplifying and increasing manufacturing yield through monolithic fabrication and enabling manufacture of microfluidic devices having a wide range of possible geometries not achievable using conventional lithographic, embossing, machining, or molding techniques.
Claims Coverage
Two independent claims were identified. The claims disclose eight main inventive features extracted from the independent claims.
High-resolution channel construction
a construction comprising one or more channels having a resolution of dimensions higher than a threshold of less than 100, 150, 200 or 250 microns
Additive manufacturing selection for resolution
the device is constructed using an additive manufacturing technique selected to provide the resolution of dimensions of the one or more channels higher than the threshold of less than 100, 150, 200 or 250 microns
Material properties for biological compatibility and imaging
the material used to construct the device provides for non-cytotoxicity over an extended period of time, optical transparency to visible light, reduced auto-fluorescence to enable data capture of the device operation via fluorescent images, and fabrication to reproduce features of less than 100 microns
Polyethyl methacrylate polymer content
the material comprises at least 50%, or 60% or 70% by weight of polyethyl methacrylate polymer or copolymer
Layered construction based on a model and parameters
the device is constructed by sequentially applying the additive manufacturing technique to a material to create a plurality of layers of the device, based on a model for the device specifying a plurality of parameters
Parameterized curing and layer thickness control
the plurality of parameters comprises a parameter for layer thickness and a predetermined parameter for curing thickness offset in the range of about 0.01 millimeters to about 0.3 millimeters
Material alternatives listed
the material comprises a polymer selected from a group consisting of polyetheretherketone (PEEK), polymethylacrylamide or polyacrylamide, polyvinylalcohol, polycaprolactone and polylactide
Channel dimensional ranges
the one or more channels have a height in the range of about 0.01 millimeters to about 2.5 millimeters and a width in the range of about 0.01 millimeters to about 2.5 millimeter
The independent claims focus on (1) microfluidic constructions with channel resolutions below specified micron thresholds, (2) selection and application of additive manufacturing techniques and layer-wise model-based fabrication parameters to achieve such resolution, (3) use of materials providing non-cytotoxicity, optical transparency, reduced autofluorescence and the ability to reproduce sub-100-micron features, and (4) material composition requirements including substantial polyethyl methacrylate content and listed polymer alternatives.
Stated Advantages
Materials and methods that produce biocompatible microfluidic devices with high degree of transparency to visible light, high-resolution features (less than 100, 150, 200 or 250 microns), and low to no autofluorescence.
Monolithic fabrication that simplifies construction, increases manufacturing yield, eliminates the need for subsequent adhesion or bonding processes, and reduces alignment and operator involvement.
Three-dimensional printing capabilities that permit curved fluidic transitions, minimized dead volumes, and a wide range of possible geometries not achievable using conventional lithographic, embossing, machining, or molding techniques.
Rapid and inexpensive iteration of prototypes enabled by additive manufacturing.
Documented Applications
Ex vivo simulation of the dynamics of cell-tissue interactions.
Microfluidic devices for culturing or testing of biological samples such as tissues, tumor cells, or other types of eukaryotic or prokaryotic cells.
A tumor analysis platform (TAP) that integrates trapping devices, bubble traps, and fluidic components to capture and sustain tumor biopsy fragments for imaging and study.
Testing the effectiveness of immunotherapy treatments on lymphocytes and tumor biopsies taken directly from a patient.
Fabrication of molds where the device is made using micromolding techniques within the device.
Supporting research activities that require extended duration studies of biological tissues under dynamic perfusion.
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