Transporter with a glucose sensor for determining viability of an organ or tissue
Inventors
MAYER, Steven L. • Kravitz, David C. • MAYER, Tracey H.
Assignees
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Publication Number
US-10420337-B2
Publication Date
2019-09-24
Expiration Date
Abstract
An apparatus for perfusing an organ or tissue includes a perfusion circuit for perfusing the organ or tissue with a perfusate; and a sensor operatively connected to the perfusion circuit. The sensor includes a solid support to which is attached a recognition molecule that permits detection of the target agent. The recognition molecule specifically binds to the target agent in the presence of the target agent but not significantly to other agents. The sensor also includes an enzyme that can catalyze the conversion of a substance to glucose. In the presence of the target agent the enzyme can convert the substance into glucose, which can then be detected and optionally measured by the sensor.
Core Innovation
The invention relates to a portable organ/tissue perfusion apparatus configured to perfuse an organ or tissue with a perfusate, including a purge flow path and a recirculating perfusate flow path. The apparatus includes a processor configured to output a determination and/or information relating to whether organs or tissues that otherwise would be discarded could be viable, and the perfusion circuit is configured to provide perfusate to the organ or tissue and to recirculate the perfusate.
A plurality of sensors are operatively connected to one or more of the flow paths, including at least a first sensor in the recirculating perfusate flow path and a second sensor in the purge flow path. Each sensor includes a solid support attached to a recognition molecule that specifically binds to a viability-indicating target agent in the perfusate, a substance that can be enzymatically converted to glucose, an enzyme that catalyzes conversion of the substance to glucose in the presence of the viability-indicating target agent, and a glucose meter configured to detect glucose produced from the substance.
The apparatus uses processor determination based on an amount of glucose detected. The viability-indicating target agent comprises one or more members selected from lactate dehydrogenase, alanine aminotransferase, β-galactosidase, TNF-α, aspartate aminotransferase, IL-8, interleukins, antioxidant biomarkers, anti-apoptotic biomarkers, tropic factor biomarkers, liver enzymes, and Kidney Injury Molecule-1 (KIM-1).
Claims Coverage
The independent claims are directed to three related apparatuses: a general organ/tissue perfusion apparatus, a kidney- or kidney-tissue-specific version with KIM-1, and a liver- or liver-tissue-specific version with liver enzymes. Across the independent claims, the core inventive features are the combination of purge/recirculation perfusion flow paths, multiple sensors distributed on those flow paths, and an enzymatically glucose-generating detection scheme linked to a viability-indicating target agent and a glucose meter, with viability determination based on an amount of glucose detected.
Perfusion circuit with purge and recirculating perfusate flow paths for viability determination
An apparatus configured to perfuse an organ or tissue with a perfusate, the perfusion circuit comprising a purge flow path and a recirculating perfusate flow path, wherein the recirculating perfusate flow path is configured to provide perfusate to the organ or tissue and recirculate the perfusate, and a processor configured to output a determination and/or information relating to whether organs or tissues that otherwise would be discarded could be viable.
Multi-sensor glucose detection using recognition binding to viability-indicating target agents
A plurality of sensors operatively connected to one or more of the flow paths of the perfusion circuit, including at least a first sensor in the recirculating perfusate flow path and a second sensor in the purge flow path, wherein each sensor includes a solid support attached to a recognition molecule specifically binding to a viability-indicating target agent in the perfusate, a substance enzymatically convertible to glucose, an enzyme catalyzing conversion in the presence of the viability-indicating target agent, and a glucose meter configured to detect glucose produced from the substance.
Substrate-to-glucose enzymatic pathway coupled to viability-indicating target agents
The substance is selected from sucrose, maltose, trehalose, starch, and cellulose, with corresponding enzyme options including invertase, sucrase, sucrase-isomaltase, maltase, trehalase, amylase, and cellulase, and the viability-indicating target agent comprises one or more members selected from lactate dehydrogenase, alanine aminotransferase, β-galactosidase, TNF-α, aspartate aminotransferase, IL-8, interleukins, antioxidant biomarkers, anti-apoptotic biomarkers, tropic factor biomarkers, liver enzymes, and KIM-1.
Viability determination based on an amount of glucose detected
The processor is configured to make the determination of whether the organs or tissues that otherwise would be discarded could be viable based on an amount of glucose detected.
Kidney perfusion apparatus with KIM-1 viability-indicating target
An apparatus configured to perfuse a kidney or kidney tissue, the perfusion circuit comprising a purge flow path and a recirculating perfusate flow path configured to provide perfusate to the kidney or kidney tissue and recirculate the perfusate, and a plurality of sensors including at least a first sensor in the recirculating perfusate flow path and a second sensor in the purge flow path, where each sensor includes a solid support attached to a recognition molecule specifically binding to a viability-indicating target agent in the perfusate, wherein the viability-indicating target agent is Kidney Injury Molecule-1 (KIM-1), and wherein the processor makes the determination based on an amount of glucose detected.
Liver perfusion apparatus with liver enzymes, lactate dehydrogenase, and alanine aminotransferase viability-indicating targets
An apparatus configured to perfuse a liver or liver tissue, the perfusion circuit comprising a purge flow path and a recirculating perfusate flow path configured to provide perfusate to the liver or liver tissue and recirculate the perfusate, and a plurality of sensors including at least a first sensor in the recirculating perfusate flow path and a second sensor in the purge flow path, where each sensor includes a solid support attached to a recognition molecule specifically binding to a viability-indicating target agent in the perfusate, wherein the viability-indicating target agent is one or more members selected from liver enzymes, lactate dehydrogenase and alanine aminotransferase, and wherein the processor makes the determination based on an amount of glucose detected.
Across the independent claims, the apparatuses share a perfusion circuit with a purge flow path and a recirculating perfusate flow path, multiple sensors positioned on those flow paths, and a glucose-generating enzymatic detection scheme that depends on specific binding to a viability-indicating target agent. In each case, the processor outputs a viability determination based on an amount of glucose detected.
Stated Advantages
Documented Applications
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