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EP-3534834-B1 - ENCAPSULATION DEVICE SYSTEMS WITH OXYGEN SENSORS WITH OR WITHOUT EXOGENOUS OXYGEN DELIVERY

EP3534834B1EP 3534834 B1EP3534834 B1EP 3534834B1EP-3534834-B1

Inventors

  • PAPAS, KLEARCHOS, K.

Dates

Publication Date
20260513
Application Date
20171103

Claims (14)

  1. A system comprising: an encapsulation device (110) comprising a lumen for holding cells surrounded by a vascularization membrane; and a first sensor (410) for real-time monitoring of a health feature of the cells or analytes housed in the encapsulation device; a second sensor (410) for real-time monitoring of a health feature of the cells or analytes housed in the encapsulation device; wherein said first sensor and said second sensor are disposed within the encapsulation device and are spaced apart such that they do not interfere with each other; and wherein the sensors are for monitoring at least one of an oxygen level and an oxygen consumption rate.
  2. The system of claim 1, wherein the first sensor and the second sensor each comprise an oxygen sensor (410) and are for measuring oxygen consumption rate of the cells housed in the encapsulation device.
  3. The system of claim 1 or claim 2, further comprising an immunoisolation membrane (130).
  4. The system of any one of the preceding claims, wherein the device comprises a port (106, 107) to access the lumen.
  5. The system of any one of the preceding claims, wherein said first sensor is on an inlet (106) of the encapsulation device and said second sensor is on an outlet (107) of the encapsulation device.
  6. The system of any one of the preceding claims, further comprising an oxygen delivery system operatively connected to the encapsulation device (110); optionally wherein the oxygen delivery system comprises an implantable oxygen generator (310, 320).
  7. The system of claim 1, wherein the first sensor is an oxygen sensor in combination with at least one of a glucose sensor, pH sensor, lactate sensor, CO 2 sensor, optical sensor, electrochemical sensor or a combination thereof.
  8. The system of any of claims 1-7, further comprising a reader (430) adapted to read the first sensor.
  9. The system of claim 8 , wherein the reader is a wireless reader (430) that is external to the skin.
  10. The system of claim 8 or claim 9, wherein the reader (430) comprises a microprocessor adapted to regulate the oxygen delivery of the oxygen delivery system.
  11. The system of any one of claims 8 to 10, wherein the first and second sensors are operatively connected to an oxygen delivery system via the reader (430).
  12. The system of any one of claims 8-11, wherein the reader (430) is not physically connected to the first or second sensor.
  13. The system of any one of claims 8-12, wherein upon receipt of a first command from the reader (430) when the reader detects an oxygen level below a threshold level, the oxygen delivery system activates and delivers oxygen to the encapsulation device.
  14. A method of detecting vascularization of an encapsulation device (110) according to any one of the preceding claims, said method comprising detecting oxygen levels via the sensors (410), wherein a difference in oxygen level between the first sensor and the second sensor is indicative of cell viability.

Description

FIELD OF THE INVENTION The present invention relates to encapsulation devices for cells (such as but not limited to islet cells, stem cell derived beta cells, or the like, e.g., for regulating blood glucose, or other cells or spheroids that can produce and release a therapeutic agent that is useful in the body), more particularly to encapsulation devices with oxygen sensors and an exogenous oxygen or gas delivery system creating a closed-loop system. BACKGROUND OF THE INVENTION The present invention features systems with encapsulation devices for cells (such as islet cells or stem cell derived beta cells or the like) and sensors for real-time monitoring of cells or analytes (such as oxygen levels, glucose levels, pH, lactate levels, carbon dioxide levels, etc.). The encapsulation devices may be loaded with cells or may be empty. The systems may be operatively connected to an oxygen generator or a gas delivery system (e.g., an air pump, a chemical oxygen generator, etc.). The sensors may be optical, electrochemical, or a combination thereof. In some embodiments, the system (e.g., encapsulation device with oxygen sensors) and oxygen generator (or gas delivery system) are in a closed loop with the sensor reader that can regulate the delivery of oxygen or other gas to the device based on the levels of oxygen that the sensor is reading from the sensors. The integration of sensors into the device (e.g., a sensor inside the device, a sensor on the outside of the device, two sensors inside the device, etc.) can help provide measurements (e.g., oxygen, glucose, lactate, pH, carbon dioxide, etc.) at various stages including, but not limited to, pre-implantation and post-implantation. In some embodiments, the systems (e.g., encapsulation devices with sensors, e.g., oxygen sensors) of the present invention are used with oxygen delivery. In some embodiments, the systems (e.g., encapsulation devices with oxygen sensors) of the present invention are used without oxygen delivery. In some embodiments, the systems (e.g., encapsulation devices with oxygen sensors) of the present invention are temporarily oxygenated. As used herein, the term "oxygen delivery" also includes gas delivery, e.g., air delivery. The term "oxygen generator" also refers to a gas generator. Without wishing to limit the present invention to any theory or mechanism, it is believed that the methods, systems (e.g., encapsulation devices with oxygen sensors), devices, and compositions of the present invention may help detect and regulate oxygen levels near or within encapsulation devices and alarm if not within the desired level. If insulin secreting cells are transplanted, the system may help regulate blood glucose by ensuring that the insulin secreting cells are properly oxygenated and therefore are able to release insulin in response to glucose in an appropriate manner. The disclosures of the following U.S. Patents are referred to: U.S. Pat. No. 5,713,888; U.S. Pat. App. No. 2003/0087427. Encapsulation devices provided with sensors are known from the documents US 2014/014226 A1, US 2003/087427 A1 and US 2004/133188 A1. SUMMARY OF THE INVENTION The invention is defined in claim 1. Further aspects and preferred embodiments are defined in the dependent claims. Any aspects, embodiments and examples of the present disclosure which do not fall under the scope of the appended claims do not form part of the invention and are merely provided for illustrative purposes. The present invention features systems with encapsulation devices for cells (such as islet cells or stem cell derived beta cells or the like) and sensors for real-time monitoring of cells or analytes or various features of the encapsulation device like oxygen levels, pH, lactate levels, etc. The systems may be operatively connected to oxygen generators or gas/oxygen delivery systems. In some embodiments, the system (e.g., encapsulation device with oxygen sensors) and oxygen generator are in a closed loop with the sensor reader that can regulate the delivery of oxygen to the device based on the levels of oxygen that the sensor is reading from the sensors. The integration of sensors into the device (e.g., a sensor inside the device, a sensor on the outside of the device, two sensors inside the device, etc.) can help provide measurements (e.g., oxygen, glucose, lactate, pH, carbon dioxide, etc.) at various stages including, but not limited to, pre-implantation and post-implantation. The present invention features a system comprising: an encapsulation device comprising a lumen for holding cells surrounded by a vascularization membrane; and a first and second sensor (two or more sensors, e.g., two sensors, three sensors, four sensors, etc.) for monitoring (e.g., real-time monitoring) of a feature of the cells housed in the encapsulation device. The sensors are for monitoring at least one of an oxygen level and an oxygen consumption rate and optionally is or a combination thereof. In some embodiments, the