Capillary network devices and methods of use
Inventors
Yoshida, Tatsuro • Shevkoplyas, Sergey S. • Burns, Jennie M.
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Assignees
Tulane University • Hemanext Inc
Member
HemanextHemanext is a privately held medical technology company specializing in oxygen-controlled red blood cell processing and storage systems for transfusion medicine. The company develops, manufactures, and commercializes innovative storage solutions that preserve the quality and function of red blood cells by limiting oxygen and carbon dioxide exposure, with the goal of improving transfusion outcomes for patients with chronic and acute conditions. Hemanext's products have received FDA De Novo marketing authorization and CE Mark certification, enabling global distribution. The company is recognized for its focus on scientific evidence, operational compatibility, and strategic partnerships with blood establishments and clinical researchers.
Hemanext is a privately held medical technology company specializing in oxygen-controlled red blood cell processing and storage systems for transfusion medicine. The company develops, manufactures, and commercializes innovative storage solutions that preserve the quality and function of red blood cells by limiting oxygen and carbon dioxide exposure, with the goal of improving transfusion outcomes for patients with chronic and acute conditions. Hemanext's products have received FDA De Novo marketing authorization and CE Mark certification, enabling global distribution. The company is recognized for its focus on scientific evidence, operational compatibility, and strategic partnerships with blood establishments and clinical researchers.
Publication Number
US-10705098-B2
Publication Date
2020-07-07
Expiration Date
Abstract
Artificial microvascular network (AMVN) devices are provided and related methods of making and methods of using such devices are provided. The present disclosure generally relates to an AMVN device comprising a substrate including a capillary network configured so as to simulate those actually encountered in the circulation of various humans and animal model systems. In certain aspects, the AMVN devices may be used, e.g., to investigate the effect of storing RBCs under aerobic and anaerobic conditions. However, the use of such AMVN devices is not so limited.
Core Innovation
The invention provides an artificial microvascular network device comprising a substrate with a capillary network that includes at least one unbranched microchannel whose cross-sectional width varies along its longitudinal axis. The unbranched microchannel ranges from 3 μm to 70 μm, comprises a longitudinal gradual taper with an initial width greater than a final width and a taper length of 5 μm to 100 μm, and further comprises a constriction followed by one or more expanded regions whose width exceeds the constriction and the final width.
The patent describes the design, fabrication, measurement and experimental validation of artificial microvascular network devices (AMVN, CND-A, CND-B) used to assess red blood cell deformability. Device geometries include inlet and outlet microchannels, constant-depth channels, capillary arrays with tapered constrictions and output extensions, and a variant with repeating constrictions and expansions. Fabrication and measurement procedures are summarized as [procedural detail omitted for safety] while emphasizing device-based perfusion and single-capillary flow metrics.
The invention further provides a method that [procedural detail omitted for safety] to measure red blood cell (RBC) deformability and compare the measured deformability to a predetermined value to select a unit of blood for extended storage. Deformability is quantified using bulk flow rate, flow in individual microchannels, plugging events or plugging frequency, RBC flux, and aggregate perfusion or flux indices to detect storage-induced decline in perfusion and to guide selection of blood units and storage or rejuvenation conditions.
Experimental results reported in the document show storage-induced increases in transient and permanent microchannel plugging and reductions in bulk perfusion. The document further reports that anaerobic storage preserves perfusion and reduces plugging relative to conventional storage.
Claims Coverage
The claim set includes two independent claims. The following inventive features are extracted from those independent claims and their characterizing elements.
Unbranched microchannel of variable size
A capillary network that comprises at least one unbranched microchannel whose cross-sectional width varies longitudinally along its length and that is in fluid communication with inlet and outlet ports for sample entry and exit.
Channel size range 3–70 μm
The at least one unbranched microchannel is specified to range in size from 3 μm to 70 μm, providing the overall dimensional bounds for the variable cross-section.
Longitudinal gradual taper
A gradual taper oriented along the longitudinal axis of the unbranched microchannel in which an initial width is greater than a final width, with a taper length ranging from 5 μm to 100 μm.
Constriction followed by expanded regions
A constriction in the microchannel followed by one or more expanded regions downstream of the constriction, wherein the expanded region width is greater than the constriction and greater than the final width of the gradual taper.
Method using CND to measure RBC deformability and select units
A method that [procedural detail omitted for safety] uses a capillary network device having the described variable unbranched microchannel geometry to measure RBC deformability, compare the measurement to a predetermined value, and select the unit of blood for extended storage.
The independent claims define (1) a capillary network device comprising at least one longitudinally variable unbranched microchannel with specified size bounds, a gradual taper, a constriction and expanded regions, and inlet/outlet ports, and (2) a method that uses such a device to measure RBC deformability and select blood units for extended storage.
Stated Advantages
Detects storage-induced decline in perfusion.
Enables selection of units for extended storage based on measured RBC deformability.
Demonstrates that anaerobic storage preserves perfusion better than aerobic storage, showing a smaller decline in perfusion by day 42.
Shows lower plugging frequency for anaerobic storage (approximately 45% lower) compared to aerobic storage in the reported experimental results.
CND-B architecture with constrictions and expansions is more sensitive than CND-A for detecting perfusion changes.
Operates at physiological hematocrit and viscosity.
Detects small non-deformable red blood cell subpopulations.
Captures dynamic microvascular behavior not measured by micropore filtration or ektacytometry.
Documented Applications
Assessing red blood cell deformability using artificial microvascular network devices.
Evaluating effects of storage conditions on red blood cell perfusion and microchannel plugging, including comparison of anaerobic and conventional storage.
Evaluating rejuvenation strategies for stored blood.
Selecting blood units for extended storage or transfusion based on measured RBC deformability.
Providing an alternative measurement approach to micropore filtration and ektacytometry for microvascular behavior assessment.
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