Method and scalable devices for hyper-fast cooling and warming
09638452 ยท 2017-05-02
Assignee
Inventors
Cpc classification
F25D3/105
MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
F17C2227/045
MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
F25D25/00
MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
F25D3/10
MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
A01N1/162
HUMAN NECESSITIES
F25D25/04
MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
F25D3/11
MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
A01N1/147
HUMAN NECESSITIES
A01N1/144
HUMAN NECESSITIES
F25D25/005
MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
F25D13/06
MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
F25D13/062
MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
A01N1/14
HUMAN NECESSITIES
International classification
F25D13/06
MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
F25D25/00
MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
F25D3/11
MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
Abstract
The present invention, in some embodiments thereof, relates to a method and scalable devices for hyperfast cooling and re-warming of samples. More specifically, it relates to cryogenic preservation of biological samples via vitrification. It includes: a liquid sample placed at ambient temperature in a flat thermo conductive container that in some embodiments additionally contains a detachable disposable or sterilizable thermo conductive spiral; transferring the sample to a cooling chamber using a linear percussion stepping motor drive; hyperfast cooling of the sample using streams of pressurized liquid coolant; transferring the sample to a detachable shipping/storage chamber filled with liquid coolant, from which the sample can be transferred to another vessel that contains liquid cryogenic coolant and moved back to the shipping/storage chamber. This chamber can be then attached to a re-warming chamber, in which the sample is heated to a biologically tolerant temperature above 0 degrees Celsius in a hyperfast manner.
Claims
1. A system for hyper-fast cooling of biological samples, comprising: a cooling chamber comprising an atomizing nozzle for directing a flow of liquid cryogenic refrigerant against a surface of a container of the biological samples for cooling the biological samples at a rate of 50,000 C/minute or greater, and further comprising a first heat insulating curtain located at a first position on a first vertical wall of the apparatus for allowing the container to pass through the first vertical wall; a storage chamber coupled to the cooling chamber by a common vertical wall, the storage chamber comprising: a holding system for storing the container after it has been hyper-cooled by the flow of liquid cryogenic refrigerant from the atomizing nozzle; and a second heat insulating curtain located at a second position on the common vertical wall in horizontal alignment with the first heat insulating curtain; and a percussion motor drive coupled to the container for propelling the container horizontally into the cooling chamber through the first heat insulating curtain, placing the container adjacent to the atomizing nozzle, and which further acts to propel the container through the common wall and into the storage chamber, via the second heat insulating curtain, after the biological samples have been hyper-cooled; and; a warming chamber, comprising; a second common wall located opposite to the common wall; a third heat insulating curtain located at a third position on the second common wall, the third heat insulating curtain in horizontal alignment with the first and second heat insulating curtains; and a heating device located adjacent to the third heat insulating curtain for heating the biological samples, the heating device comprises a magnetic field source; wherein the percussion motor drive is further configured to extend the container horizontally through the storage chamber and into the warming chamber.
2. The system of claim 1, wherein the first and second heat insulating curtains comprise a split for allowing the container to pass, and installed with an ability to rotate around a horizontal axis located above each of the curtains.
3. The system of claim 1, wherein guide pin is connected to the container by a ball clamp.
4. The system of claim 1, wherein the container comprises a flat-ended box comprising a bottom panel made of a heat conductive material, and a top cover that is made from an optically transparent material.
5. The system of claim 1, wherein the holding system comprises a fixed portion and a moving portion that captures the container.
6. The system of claim 1, wherein the cooling chamber further comprises a deflector for deflecting the flow of liquid cryogenic refrigerant flow.
7. The system of claim 1, wherein the atomizer nozzle is installed at an angle with respect to a bottom surface of the container.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
(10)
(11)
(12)
(13)
(14)
(15)
(16)
(17)
(18)
(19)
(20)
(21)
(22)
(23)
(24)
(25)
(26)
(27)
(28)
(29)
(30)
(31)
(32)
(33)
(34)
(35)
(36)
(37)
(38)
(39)
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION
(40) Presented device can be made using a linear percussion stepping motor drive and using a motor drive which provides linear and rotary motion.
(41) Consider a device that uses linear percussion stepping motor drive.
(42) Presented device of specimen hyper-fast cooling and heating, using cryogenic refrigerant consists of linear percussion stepping motor drive 1, located in zone 2 with environment temperature, container 3 with biological specimen 4, which is connected to motor drive 1 by guide pin 5. Along the container 3 moving direction at the speed V, contiguous with each other cooling vessel 6 and storage vessel 7 and active zone of heating device 8 are located. Adjacency is achieved by mentioned vessels sharing the same walls. Vessels 6 and 7 are made from heat insulating material, like solid plastic foam, for example.
(43) In cooling vessel 6 nozzle 9 with atomizer 10 on its end is installed, providing upflow jets 11 of liquid cryogenic refrigerant, such as liquid nitrogen for example. Above atomizer 10 flow jets deflector 12 is secured, so there is an opportunity of non-contact transfer and locating container 3 between atomizer 10 and deflector 12.
(44) Container 3 is performed in the shape of flat box, which bottom panel 13 is thin and made from heat conductive material, such as copper, for example, and top cover 14 is made of optically transparent material. Guide pin 5, made from heat insulating material, such as glass fiber plastic, connected to container 3 by ball clamp 15.
(45) On the side walls of cooling vessel 6 and storage vessel 7 optically transparent vacuum windows 16 are installed (
(46) Heating device, located in zone 2 with environment temperature, contains source of HP magnetic field 19, covering inside space of mentioned device.
(47) Lower the level of cooling vessel 6 and storage vessel 7, containment vessel 20 with liquid nitrogen 21 is located. Vessel 20 is made as cryostat, withstanding increased internal pressure.
(48) At the top part of vessel 20, heater 22, excessive pressure release valve 23, and insulated nozzles 9 and 24 connected to vessels 6 and 7 respectively are located. On nozzles 9 and 24 shutoff valves 25 and 26 are installed respectively. Heater 22 can be electric for example with controlled intensity of current.
(49) Excessive pressure releasing valve 23, is equipped with operation level adjustment (not shown on the drawing), which allows to control pressure tolerance of refrigerant in containment vessel 20, preventing its mechanic damage from extremely high pressure.
(50) Outlet of valve 23, valve 17 of cooling vessel 6 and outlet 18 of storage container 7 are connected to pipeline (not shown on the drawing), which end is located in environment temperature zone outdoors (not shown on the drawing), where device for hyper-fast cooling and heating of specimen is located. It allows to discharge gaseous nitrogen from vessel 6, 7 and 20 to environment, instead of indoors, providing safe atmosphere for maintenance staff.
(51) Storage vessel 7 contains holding system 27 for container 3, including fixed part 28 and moving part 29.
(52) On vertical walls 30, 31, and 32 of vessels 6, 7 and 18 along moving direction of container 3 at the speed V, heat insulating curtains 33, 34 and 35 are located respectively (
(53)
(54) Inside internal openings of inductor 39, anchoring block 40 and power disc 41, guide pin 5 is located, containing row of distributed along the axis elastic stops 45, made with ability to be compressed by power disc while moving under pullback spring 42 pressure. Elastic stop 45, having triangle shape in section for example, connected to guide pin 5 with spring 46, contiguous to its vertical side, and to axis 47, located on the corner of the moving direction of container at the speed V (
(55) Inductor 39 is performed as solid multistranded disk coil, impregnated with epoxide compound. Conductive anchoring block 40 is made in the shape of copper click with outer diameter, matching outer diameter of inductor 39. Power disc 41 is made of sound material such as stainless steel with outer diameter, matching outer diameter of anchoring block.
(56) On
(57) Two sectioned starter device (
(58)
(59) Consider a device of specimen hyper-fast cooling and heating, using motor drive which provides linear and rotary motion (
(60) A device of specimen hyper-fast cooling and heating, using cryogenic refrigerant consists of motor drive 1, which provides linear and rotary motion, located in zone 2 with environment temperature, container 3 with biological specimen 4, which is connected to motor drive 1 by guide pin 5
(61) Guide pin 5 is introducing into cooling vessel 6 via split/hole (not shown on the drawing) which shuttled off with moving heat insulating curtain 59 at its/cooling vessel's cover lid 60. A sectional end unit 61 is installed with elastic clamps 62 at the end of pin 5. Central pivot/rod 63 of guide pin 5 is located in central split/hole (not shown on the drawing) of end unit 61 with a ledge beyond/outside its end surface (
(62) Container 3 is connected to the sectional end unit 61 of guide pin 5 with a bar 64 with ability of mutual transferring, for example in axial direction. To the guide pin 5 connects a heat insulating capsule 65 meant for encasing /to encase of container 3 and made from plastic foam for example, with a bar 66 with ability of mutual transferring.
(63) Cooling vessel 3 is equipped with nozzle 17 for gaseous nitrogen outlet. Inside cooling vessel 6 nozzle 9 is installed, with two opposite atomizers 10 on its end with gap for non-contact transfer container 3. Flat-ended container 3 in gap is encasing from opposite sides by two atomizers 10, the distance between them is less than matching dimensions of heat insulation capsule 65 (
(64) Container 3 is performed in the shape of flat-ended box which panels are thin and made from heat conductive material, such as copper, for example (
(65) Nozzle 9 with a shutoff valve 25 is going out of pressure-tight vessel 20, which is made as cryostat, withstanding increased internal pressure, with liquid nitrogen 21. At the top part of vessel 20, heater 22, increased pressure of gaseous nitrogen release valve 23 are located. Valve 23 is equipped with operation level adjustment (not shown on the drawing), which allows to control pressure tolerance of gaseous refrigerant in containment vessel 20, preventing its mechanic damage from extremely high pressure.
(66) Valves outlet 23 is connected to the pipeline 67, which end is located in environment temperature zone, outdoors (not shown on the drawing) with device for hyper-fast cooling and heating of specimen. It allows to discharge gaseous nitrogen from vessel 20 to environment, instead of indoors, providing safe atmosphere for maintenance staff.
(67) Lower the level of cooling vessel 6, cryogenic vessel 68, Dewar vessel for example, is installed, for discharge liquid refrigerant 21 from vessel 6 with nozzle 69, which determines the level of liquid refrigerant in vessel 6, and nozzle 70 with valve 71, meant for complete discharge liquid refrigerant 21 from vessel 6.
(68) Storage vessel 7 can be installed both inside cooling vessel 6 (
(69) Vessel 7 contains holding system 27 for container 3, which includes fixed 28 and moving 29 units. Moving unit of holding device 27 consists of sections 73 with spot splits 74 for end units 61 of guide pin 5 (
(70) Inside heating vessel 72 two elements 78 of heating device 19 are located with gap for non-contact transfer container 3 (
(71) Storage vessel 7 contains handle 79, which allows place and take out the vessel both in cooling vessel 6 and in heating vessel 72.
(72) Guide nozzles 80 of atomizer 10 which are forming liquid refrigerant jets 11, are installed at the angle a to the atomizer surface, located parallel to the surface of a flat-ended container (
(73) Container 3 (
(74) Space between the turn of spiral 84 can be filled with the liquid specimen 4 with the syringe 85, the end (or a needle) of which can be inserted in the container through the inlet valve 81, which can containe selef-sealing material such as a resin or rubber. The upper cover (lid) 14 of the container 3 is hermetically connected with the side walls of the container 83 hermetically. In one of embodiments, the upper cover (lid) 14 can be made of a smart material with an alloy opr plastic with thermal shape memory. The upper cover (lid) can be easily removed in working ambient but self-sealed hermetically with the walls at if cooled below the transition point.
(75) The filling of the container 3 can be made as following: The end (or needle) of the syringe 85 filled with liquid specimen 4 is placed into the inlet valve 82 (
(76) Device using linear percussion stepping motor drive (
(77) Linear percussion stepping motor drive 1 is to be initialized.
(78) If mentioned motor drive 1 is made as coaxial linear pulse motor drive of induction type (
(79) Capacitive energy storage is to be charged.
(80) If indicated motor drive is performed as coaxial starter device of telescopic type, for example tree sectioned (FIG.14), external 48, intermediate 49 and internal cylinder 50 are encasing each other. With that springs 52, 53 and 54 are being compressed and held by controlled clamps, 55, 56 and 57 respectively.
(81) In two section coaxial starter device of telescopic type (
(82) In initial condition shutoff valves 25, 26 and releasing valves 23 are to be closed, to provide sealing of the vessel 20 with liquid nitrogen 21. After, electric heater 22 is to be turned on, which leads to increased evaporation of liquid nitrogen and pressure increase of gaseous nitrogen in sealed vessel 20.
(83) In environment temperature zone 2, container 3 is getting prepared. For this biological specimen 4 is placed in flat box with bottom panel 13, which is tightly closed by cover lid 14. Then container is to be connected to guide pin 5 (
(84) After this, shutoff valve 25 is to be opened. Under increased pressure of gas in sealed vessel 20 liquid nitrogen 21 is going through nozzle 9 under head, coming out of atomizer 10, entering cooling vessel 6. At first in gaseous state, then in a form of jets 11, liquid nitrogen flow is affecting flow deflector 12, which receives their mechanical energy. Evaporated gaseous nitrogen is going out through nozzle 17 from cooling vessel 6 to environment temperature zone 2, ensuring remaining of atmosphere pressure in vessel 6.
(85) Process of liquid nitrogen jets 11 appearing can be watched through vacuum window 16, installed on the side wall of cooling vessel 6 (
(86) After linear percussion stepping motor drive 1 is initiated.
(87) If motor drive is performed as coaxial linear pulse motor drive of induction type (
(88) If motor drive 1 is performed as two-sectioned coaxial starter device of telescopic type (
(89) After starting linear percussion stepping motor drive 1, container 3 quickly transfers from environment temperature zone 2 to cooling vessel 6 (
(90) After discharging process is finished currents in inductor 39 and electro conductive anchoring block 40 decay and electrodynamic force between them goes to zero. Compressed pullback spring 42, when being released returning power disc 41 and anchoring block 40 to original positions at the speed v, toward inductor 39 (
(91) In vessel 6 container is going under liquid nitrogen inclined upflow 11, which is affecting bottom panel 13 of flat ended container 3 (
(92) Evidence of container 3 complete refrigeration is absence of vapor film on flat ended container 3 bottom panel 13, when it's fully immerged in liquid nitrogen 21.
(93) After vessel 6 is filled with liquid nitrogen, shutoff valve 25 is to be closed and supply of liquid nitrogen to filled cooling vessel 6 stops. (
(94) After this, under power pulse action, created by linear percussion stepping motor drive 1, container 3 transfers to filled with liquid nitrogen 21 storage container 7 from neighboring cooling vessel 6 (
(95) If motor drive 1 is performed as two sectioned coaxial starter device of telescopic device (
(96) For container 3 prolonged storing in vessel 7, where there's room for various manipulation with vessel 7, such as transportation, transfer to different conditions and others, fixed part 28 of holding system 27 is to be closed by moving element 29 (
(97) If necessary to hyper-fast heat biological specimen 4, following actions are to be performed.
(98) Electric heater 22 is to be turned off, shut off valves 25 and 26 are to be closed, and pressure release valve 23 is to be opened. So gaseous nitrogen of increased pressure is going out from containment vessel 20 through valve 23 to environment temperature zone 2. After gas pressure equalizing in zone 2 and in vessel 20 shutoff valves 25 and 26 are to be opened and liquid nitrogen from cooling vessel 6 and storage vessel 7 is to be drained to containment vessel. 20 (
(99) After this, under power pulse action, created by linear percussion stepping motor drive 1, container 3 transfers from neighboring storage vessel 7 to active zone of heating device 8, where HP magnetic field is created before by source 19 (
(100) While container 3 is going through walls 31 and 32, between vessels 6 and 7, 7 and 8 heat insulating curtains 34 and 35 are acting similar to curtain 33 when going through wall 30.
(101) Hyperast heating of biological specimen 4 located in container 3 is possible because of: active zone of heating device 8, is located in environment temperature zone 2, which significantly exceeding liquid nitrogen temperature in vessel 7; HP magnetic field, created by the source 19, is heating biological specimen 4 directly; HP magnetic field, created by the source 19, is heating bottom panel 13 of container 3, which made from copper, and the panel is heating specimen 4 by thermal conductivity.
(102) After biological specimen 4 achieved environment temperature, HP magnetic field source 19 is to be turned off and container 3 is to be transferred by linear percussion stepping motor drive 1, from active zone of heating device 8 to zone 2 (not shown on the drawing).
(103) In storage device and hyper-fast heating device of specimen (
(104) In presented device low flow of liquid nitrogen is assured by its multiple transfer from containment vessel to cooling vessel and storage vessel and back, which makes the process cost efficient.
(105) The process of cooling and manipulation in cooling and storage vessel is producible and controlled visually through vacuum windows 16 on every basic stage, which allows to modify conditions of the process such as jets speed in cooling vessel and others.
(106) Device of hyper-fast cooling and heating of specimen, using motor drive with linear and rotary motion (
(107) In initial condition valves 23, 25 and 71 are to be closed, and heater 22 is to be turned on. Thereby increased pressure of gaseous nitrogen creates in containment vessel 20.
(108) Guide pin 5 with sectional end unit 61 raises, and to it container 3 biological specimen is secured with bar 64 and heat-insulated capsule 65 is secured with bar 66 (
(109) After valve 25 gets opened and increased pressure liquid nitrogen 21 comes in cooling vessel 6 from containment vessel 20 via atomizers 10 of nozzle 9. Evaporated gaseous nitrogen is going out through nozzle 17 from vessel 6. If level of liquid nitrogen 21 in vessel 6 exceeds top piece of nozzle 69, it discharges in cryogenic vessel 68.
(110) After, moving heat insulating curtain 59 is being displaced sideways, split at cover lid 60 of cooling vessel 6 is being opened, and motor drive 1 with guid pin 5 provides linear transferring at the speed V container 3 together with heat insulating capsule 65 inside vessel 6.
(111) After sectional end part 61 of pin 5 contacts with container holding system 27, container is turned with speed , for example 90 (
(112) After contact of sectional/detachable end piece 61 of pin 5 with a moving part 29 of holding system 27, central pivot 63 ends up/is going in holding/fixing split 74 of section 73 of moving part 29. Stop 77, under effect central pivot 63 of guid pin 5, is pressed down and releases matching stop 76 of section 73 (
(113) Moving insulating curtain 59 returns to original position, and split closes at cover lid 60 of cooling vessel 6.
(114) After cooling container 3 to the temperature of liquid nitrogen, guide pin 5 further is turned, and container 3 with bar 64 (bar on
(115) Guide pin 5 detaches from end unit/piece 61 and raises with heat insulating capsule 65. Elastic clamps 62 are being compressed, providing sinking bar 64 with container 3 down to storage vessel 7 (
(116) After the end of containers 3 cooling process, valve 71 is to be opened and liquid nitrogen 21 through nozzle 70 is discharged from cooling vessel 6 to cryogenic vessel 68.
(117) Cover lid 60 is to be opened and with handle 79 storage vessel 7 with containers 3 is taking out from vessel 6 and is transferring in necessary place, in cryogenic transport vessel for example (not shown on the drawing).
(118) If necessary, fast heating storage container 7 with handle 79 is transferring inside heating vessel 72. Motor drive 1 is putting down guid pin 5 into vessel 72 till it is contacting and joining with end part 61. After with guid pin 5 and bar 64, container 3 is raising and turning, beyween two elements 78 of heating device 19, untill entering into the gap (
(119) A container 3 (
(120) Ultra-high rates of cooling of biological specimens are achieved by: contact of numerous liquid nitrogen jets, with significant motional energy, on all wide, flat area of cooled biological specimen through thin copper wall of container; short life of vapor phase (film boiling) on the contact border of liquid nitrogen with biological specimen; force removal of vapor phase by directed flow of liquid nitrogen (under pressure); percussive-dropping cooling by multiple contacts of liquid nitrogen with biological specimen surface.