BIOREACTORS, SYSTEMS, AND METHODS FOR PRODUCING AND/OR ANALYZING ORGANS
Articles and methods for growing or analyzing tissues and organs using bioreactors or other devices and components are provided. In some embodiments, a bioreactor is configured to provide a growth chamber having one or more inlets, outlets, sensors, organ attachment sites, and/or organ identifiers.
1 . A bioreactor comprising,
a chamber configured for containing an organ under culture conditions,
a first inlet port and a first outlet port in fluid communication with the chamber, and
an organ support structure disposed in the chamber.
2 . The bioreactor of claim 1 , wherein the organ support structure is connected to a scale or gauge for measuring the weight of the organ; or wherein the organ support structure comprises a platform, optionally wherein the platform is shaped to receive the lower portion of an organ; or wherein the organ support structure comprises a first support member, optionally wherein the first support member comprises a hook; or wherein the organ support structure comprises a first tubular connector adapted for attaching a vascular structure.
3 - 7 . (canceled)
8 . The bioreactor of claim 2 , wherein the first tubular connector is cylindrical; or wherein the first tubular connector comprises a flexible flange; or wherein the first tubular connector comprises an elastic flange; or wherein the first tubular connector comprises an expandable flange, optionally wherein the expandable flange is remotely controlled; or wherein the first tubular connector comprises a tapered end; or wherein the first tubular connector comprises a flared end.
9 - 14 . (canceled)
15 . The bioreactor of claim 1 , wherein the organ support structure is in a fixed position relative to the chamber; or wherein the organ support structure can rotate around a first axis that is in a fixed position relative to the chamber; or wherein the organ support structure can rotate around a second axis that is in a fixed position relative to the chamber.
16 - 17 . (canceled)
18 . The bioreactor of claim 1 , further comprising one or more sensors responsive to pressure, flow, pO2, pH, CO2, lactate, glucose, electrical, ion concentration, mechanical force, torque, stretch, fluorescence, emissivity, vibrational properties and/or response to external energy, and/or temperature.
19 - 24 . (canceled)
25 . The bioreactor of claim 1 , wherein the chamber wall comprises a sterile access port; or wherein the chamber wall comprises an observation area that is transparent to infrared, UV, and/or visible light; or wherein the chamber wall comprises a translucent portion, optionally wherein the translucent portion comprises polysulfone or any other sterilizable material that is transparent to infrared and/or visible wavelengths; or wherein the chamber wall comprises a flexible portion, optionally wherein the flexible portion can be used to limit the distance of the fluid barrier between an organ and a detector to less than about 3 mm; or wherein the chamber wall comprises a section of elastic material.
26 - 35 . (canceled)
36 . The bioreactor of claim 1 , further comprising a first stimulatory means,
optionally wherein the first stimulatory means can administer an electrical challenge to a substitute organ attached to the organ support structure, and optionally further comprising a sensor capable of detecting a response to the electrical challenge; or
optionally wherein the stimulatory means can administer a chemical challenge to a substitute organ attached to the organ support structure, and optionally further comprising a sensor capable of detecting a response to the chemical challenge; or
optionally wherein the stimulatory means can administer a physical or mechanical challenge to a substitute organ attached to the organ support structure, and optionally further comprising a sensor capable of detecting a response to the physical challenge.
37 - 44 . (canceled)
45 . The bioreactor of claim 36 , wherein the challenge represents a physiological parameter selected from the group consisting of blood pressure, pH, oxygen, toxin, metabolite, airflow, substrate, force, torque, hormone, and any combination thereof; or wherein the response is a level of a physiological parameter selected from the group consisting of blood pressure, pH, oxygen, toxin, metabolite, and any combination thereof that can be measured using any mechanical, optical, and/or chemical sensor.
46 . (canceled)
47 . The bioreactor of claim 1 , further comprising a 2-dimensional or 3-dimensional array of sensors to determine the size, shape, weight, tensile strength, blood vessel strength, or strength of attachment to a substrate of a substitute organ attached to the organ support structure, wherein the sensors can detect any mechanical, optical, and/or chemical signal.
48 - 53 . (canceled)
54 . The bioreactor of claim 1 , further comprising a substitute organ attached to the organ support structure, optionally including a sensor capable of detecting a response to an electrical challenge, a chemical challenge or a physical challenge; or, further comprising a scaffold attached to the organ support structure, optionally wherein the scaffold is a decellularized organ scaffold.
55 - 56 . (canceled)
57 . The bioreactor of claim 54 , wherein the substitute organ is a substitute solid or hollow organ, optionally wherein the substitute solid or hollow organ is a substitute lung, liver, kidney, heart, or pancreas.
58 - 61 . (canceled)
62 . The bioreactor of claim 1 , further comprising a first tag for identifying, tracking, or confirming the origin of a substitute organ attached to the organ support structure, optionally wherein the first tag is an electronic tag, a magnetic tag, an RFID tag, a barcode, or any combination thereof.
63 . (canceled)
64 . The bioreactor of claim 1 , further comprising a means for removing cells from the chamber to identify, track, or confirm the origin of a substitute organ attached to the organ support structure.
65 . The bioreactor of claim 1 , further comprising an injector for injecting material into a substitute organ attached to the organ support structure.
66 . The bioreactor of claim 1 , further comprising a biopsy device for removing material from a substitute organ attached to the organ support structure.
67 . A system comprising a bioreactor of claim 1 connected to a pump via one or more conduits, wherein each of the chamber, pump, and one or more conduits are of material that is compatible with use with an MRI, CAT, PET, X-ray analysis, or ultrasound device.
68 . A system of claim 67 , wherein the material of each of the chamber, pump, and one or more conduits is non-metallic, and/or non-paramagnetic.
69 - 71 . (canceled)
72 . A kit comprising a first tag to be attached to an organ recipient and a second tag to be attached to a bioreactor or system of claim 67 or to a substitute organ within said bioreactor.
73 . (canceled)
74 . The kit of claim 72 , wherein the first and second tags are independently selected from an electronic tag, a magnetic tag, and RFID tag, a barcode, or any combination thereof.
75 - 79 . (canceled)
80 . The bioreactor of claim 1 , wherein the chamber has a volume of between 20 cc and 20,000 cc, between 500 cc and 1,000 cc, between 1,000 cc and 10,000 cc, between 10,000 cc and 20,000 cc, or larger.
81 - 338 . (canceled)