System for and method of freezing biological tissue

• US 4,117,881 A
• Filed: 06/14/1977
• Issued: 10/03/1978
• Est. Priority Date: 06/14/1977
• Status: Expired due to Term

• Current Assignee: United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration
• Original Assignee: United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration
• Inventors: Williams, Thomas E., Cygnarowicz, Thomas A.
• Primary Examiner(s): Myhre, Charles J.
• Assistant Examiner(s): LaTulip, Margaret A.
• Application Number:
  US05/806,440
• Time in Patent Office: 476 Days
• Field of Search: 165/2, 165/30, 236/78 B, 128/1 R, 62/78, 62/514 R, 195/1.8, 219/30 R, 219/328, 219/299
• US Class Current: 435/1.3
• CPC Class Codes: A61M 1/0272 Apparatus for treatment of blood or blood constituents prior to or for conservation, e.g. freezing, drying or centrifuging
• CPC Class Codes: A61M 1/0277 Frames constraining or supporting bags, e.g. during freezing
• CPC Class Codes: A61M 2205/3606 cooled
• CPC Class Codes: A61M 2205/362 by gas flow
• CPC Class Codes: A61M 2205/3653 by Joule effect, i.e. electric resistance
• CPC Class Codes: F25D 29/001 for cryogenic fluid systems
• CPC Class Codes: G05D 23/1904 variable in time

Abstract

Blood cells, blood marrow, and other similar biological tissue is frozen while in a polyethylene bag placed in abutting relationship against opposed walls of a pair of heaters. The bag and tissue are cooled with refrigerating gas at a time programmed rate at least equal to the maximum cooling rate needed at any time during the freezing process. The temperature of the bag, and hence of the tissue, is compared with a time programmed desired value for the tissue temperature to derive an error indication. The heater is activated in response to the error indication so that the temperature of the tissue follows the desired value for the time programmed tissue temperature. The tissue is heated to compensate for excessive cooling of the tissue as a result of the cooling by the refrigerating gas. In response to the error signal, the heater is deactivated while the latent heat of fusion is being removed from the tissue while the tissue is changing phase from liquid to solid.

Claims

1. A method of freezing blood cells, bone marrow, and other similar biological tissue located in a container against opposed walls of a pair of heaters, said container having a high thermal conductivity so that the tissue and container are at substantially the same temperature, comprising cooling the container with refrigerating fluid at a time programmed rate at least equal to the maximum cooling rate needed at any time during the freezing process, monitoring the temperature of a surface of the container to derive an indication of the tissue temperature, comparing the indication of the tissue temperature with a time programmed desired value for the tissue temperature to derive an error indication, and activating the heaters in response to the error indication so that the temperature of the tissue follows the desired value for the time programmed tissue temperature.

2. The method of claim 1 wherein the container is a polyethylene bag.

3. The method of claim 1 wherein the bag has a relatively narrow width in a direction at right angles to its longitudinal axis, and flowing the fluid in the direction of said axis.

4. A method of freezing blood cells, bone marrow and other similar biological tissue comprising cooling the tissue with refrigerating fluid supplied to the tissue at a time programmed rate at least equal to the maximum cooling rate needed at any time during the freezing process, heating the tissue to compensate for excessive cooling of the tissue as a result of the cooling by the refrigerating fluid, and preventing heating of the tissue while the latent heat of fusion is being removed from the tissue while it is undergoing a change of state from liquid to solid.

5. A method of freezing blood cells, bone marrow and other similar biological tissue, comprising cooling the tissue with refrigerating fluid at a time programmed rate at least equal to the maximum cooling rate needed at any time during the freezing process, deriving an indication of tissue temperature, comparing the indication of the tissue temperature with a time programmed desired value for the tissue temperature to derive an error indication, and heating the tissue in response to the error indication so that the temperature of the tissue follows the desired value for the time programmed tissue temperature.

6. Apparatus for freezing blood cells, bone marrow and other similar biological tissue adapted to be placed in a container having a high thermal conductivity so that the tissue and container are at substantially the same temperature, comprising a heater having a pair of opposed heating walls against which the container is adapted to abut, means for cooling the container with refrigerating fluid at a time programmed rate at least equal to the maximum cooling rate needed at any time during the freezing process, means for monitoring the temperature of a surface of the container to derive an indication of tissue temperature, means for comparing the indication of the tissue temperature with a time programmed desired value for the tissue temperature to derive an error indication, and means for activating the heater in response to the error indication so that the temperature of the tissue follows the desired value for the time programmed tissue temperature.

7. The apparatus of claim 6 wherein the heater includes a pair of metal plates forming the opposed heating walls, an electric heater responsive to the activating means on each of said plates remote from each heating wall, said walls being flat and parallel to each other and having a gap between them so that flat, parallel faces of the container abut against them.

8. The apparatus of claim 7 wherein the plates are located in the path of the fluid so that the fluid flows at right angles to the width of the gap.

9. The apparatus of claim 7 further including a controller for the heater responsive to the temperature monitoring means, said controller including means for comparing a first signal indicative of the monitored temperature with a desired tissue temperature to derive a control signal having a duty cycle directly proportional to the deviation between the load and the desired temperature, an electric switch for selectively connecting the heater to an AC power source that is connected to the switch to cut off the switch during each cycle of the power source, the power source having a period much less than each period of the control signal so that many cycles of the power source occur during one cycle of the control signal, said switch being responsive to the control signal so that the switch is activated to connect the power source to the heater during a portion of each cycle of the control signal while the duty cycle of the control signal is being derived, whereby the heater is cut off and activated with a response time determined by the frequency of the power source to heat the tissue to compensate for excessive cooling of the tissue by the refrigerating fluid and to prevent heating of the tissue while the latent heat of fusion is being removed from the tissue while it is undergoing a change of state from liquid to solid.

10. The apparatus of claim 9 wherein the means for deriving the control signal includes means for comparing the first signal wiith the desired tissue temperature to derive an error signal having an amplitude directly indicative of the deviation, a periodic linear waveform source having a relatively long period, means for comparing the amplitudes of error signal and the waveform to derive a control signal having a duty cycle over each period of the waveform directly proportional to the magnitude of the deviation.

11. Apparatus for freezing blood cells, bone marrow and other similar biological tissue comprising means for cooling the tissue with refrigerating fluid at a time programmed rate at least equal to the maximum cooling rate needed at any time during the freezing process, means for deriving an indication of tissue temperature, means for comparing the indication of the tissue temperature with a time programmed desired value for the tissue temperature to derive an error indication, and means for heating the tissue in response to the error indication so that the temperature of the tissue follows the desired value for the time programmed tissue temperature.

12. The apparatus of claim 11 wherein the heater includes a pair of metal plates forming the opposed heating walls, an electric heater responsive to the error indication on each of said plates remote from each heating wall, said walls being flat and parallel to each other and having a gap between them so that flat, parallel faces of a container for the tissue abut against them.

13. The apparatus of claim 12 wherein the plates are located in the path of the fluid so that the fluid flows at right angles to the width of the gap.

14. Apparatus for controlling the temperature of a load to a high resolution, said load being located in a refrigerator adapted to freeze the load, comprising means for sensing the temperature of the load to derive a first signal indicative of the load temperature, means for comparing the first signal with a desired load temperature to derive a control signal having a duty cycle directly proportional to the deviation between the load and desired temperatures, an electric heater for heating the load, an electric switch for selectively connecting the heater to an AC power source that is connected to the switch to cut off the switch during each cycle of the power source, the power source having a period much less than each period of the control signal so that many cycles of the power source occur during one cycle of the control signal, said switch being responsive to the control signal so that the switch is activated to connect the power source to the heater during a portion of each cycle of the control signal while the duty cycle of the control signal is being derived.

15. The apparatus of claim 14 wherein the means for deriving the control signal includes means for comparing the first signal with the desired load temperature to derive an error signal having an amplitude directly indicative of the deviation, a periodic linear waveform source having a long period relative to the period of the AC power source, means for comparing the amplitudes of the error signal and the waveform to derive a control signal having a duty cycle over each period of the waveform directly proportional to the magnitude of the deviation.