ELIMINATION OF VIRUSES IN BLOOD THROUGH MICROWAVE TECHNIQUES

Abstract

Heat treatment apparatus for inactivating viruses in blood includes a series of four tubing coils with connectors at the opposite ends of the series for connecting the tubing to a blood source and a blood destination, a microwave heating chamber arranged to receive the first coil of the series, a dwell chamber to receive the second coil of the series, a cooling chamber adapted to receive the third coil of the series, and a microwave reheating chamber to receive the fourth coil of the series, with the first, second, and fourth chambers employing microwave energy for heating the blood as it flows within the coils and providing a radiometer circuit for monitoring the temperatures of the blood in the first, second, and fourth coils to produce first, second, and fourth temperature signals in response thereto, which is responded to by a controller to control the energy producing means to impart a selected time/temperature profile to the blood flowing through the tubing and to deliver that blood at a selected delivery temperature.

Claims

1. A heat treatment apparatus for achieving viral inactivation in blood, said apparatus comprising a length of small diameter dielectric tubing having opposite ends and formed into a series of coils including a first coil, a second coil, and a third coil; a first connector mounted to a first end of the tubing for connecting the tubing to a blood source and a second connector mounted to a second end of the tubing for connecting the tubing to a blood destination; flow means for flowing blood product from said blood source within said tubing from the first end of the tubing to the second end of the tubing at a selected flow rate; a first electromagnetic heating chamber enclosing said tubing, said chamber having an access opening receiving said first coil into said first electromagnetic heating chamber; a first energy producing means connected to said first electromagnetic heating chamber for providing electromagnetic energy to said first electromagnetic heating chamber to heat the blood flowing in said first coil from an initial temperature to a selected elevated temperature sufficient for viral inactivation; a dwell chamber enclosing said tubing, said chamber having an access opening receiving said second coil into said dwell chamber; a second energy producing means connected to said dwell chamber for providing energy to said dwell chamber to maintain the blood flowing in said second coil at said selected elevated temperature sufficient for viral inactivation; a cooling chamber adjacent to said second heating chamber and enclosing said tubing, said cooling chamber having an access opening for receiving said third coil into said cooling chamber; cooling means connected to said cooling chamber for cooling the blood flowing in the third coil; means in said first electromagnetic heating chamber, said dwell chamber, and said cooling chamber for radiometrically monitoring the temperatures of the blood flowing in said first, second, and third coils, and producing first, second, and third temperature signals in response thereto; and control means connected to said monitoring means and responsive to the first, second, and third temperature signals for controlling the flow means, energy producing means and/or cooling means to impart a selected time-temperature profile to blood flowing within the tubing.

2. The heat treatment apparatus of claim 1 wherein the length of tubing further includes a fourth coil, said fourth coil located between the third coil of the tubing and the second end of the tubing; the heat treatment apparatus further comprises a second electromagnetic heating chamber adjacent to the cooling chamber and having an access opening for receiving said fourth coil into said second electromagnetic heating chamber, a third energy producing means connected to said second electromagnetic heating chamber for providing electromagnetic energy to said second electromagnetic heating chamber to heat the blood flowing in said fourth coil, and means in said second electromagnetic heating chamber for radiometrically monitoring the temperature of the blood flowing in said fourth coil, and producing a fourth temperature signal in response thereto; and the control means further delivers the blood to the fourth coil at a selected temperature below body temperature and controls the third energy producing means in response to the fourth temperature signal so as to reheat the blood flowing in the fourth coil to body temperature whereby the body temperature is approached from below.

3. The heat treatment apparatus of claim 1 wherein the blood source is a patient, wherein the first connector interacts with a blood extraction means, said blood extraction means suitably configured to extract blood from the patient in a substantially continuous manner; and the blood destination is the patient, wherein the second connector interacts with a blood reintroduction means, said blood reintroduction means suitably configured to reintroduce blood into the patient in a substantially continuous manner.

4. The heat treatment apparatus of claim 1 wherein the first electromagnetic heating chamber further comprises an inlet waveguide and an outlet waveguide; and the first energy producing means comprises a microwave transmitter coupled to the first electromagnetic heating chamber by way of a probe that projects into said chamber.

5. The heat treatment apparatus of claim 1 wherein the second energy producing means provides electromagnetic energy to said dwell chamber; the dwell chamber further comprises an inlet waveguide and an outlet waveguide; and the second energy producing means comprises a microwave transmitter coupled to the dwell chamber by way of a probe that projects into said chamber.

6. The heat treatment apparatus of claim 1 wherein the dwell chamber is insulated and preheated to the selected elevated temperature sufficient for viral inactivation by the second energy producing means.

7. The heat treatment apparatus of claim 1 wherein the cooling chamber comprises an inlet tube and an outlet tube; and the cooling means comprises a coolant that is introduced into the cooling chamber through the inlet tube and circulated through the cooling chamber and then removed from the cooling chamber through the outlet tube.

8. The heat treatment apparatus of claim 2 wherein the second electromagnetic heating chamber further comprises an inlet waveguide and an outlet waveguide; and the third energy producing means comprises a microwave transmitter coupled to the second electromagnetic heating chamber by way of a probe that projects into said chamber.

9. The heat treatment apparatus of claim 1 wherein the flow means comprises a paristoltic pump.

10. The heat treatment apparatus of claim 1 wherein the selected elevated temperature of the blood achieved by the first energy producing means is within the range of 75° C. to 85° C.

11. The heat treatment apparatus of claim 1 wherein the selected elevated temperature of the blood maintained within the dwell chamber is within the range of 75° C. to 85° C.

12. The heat treatment apparatus of claim 1 wherein the temperature of the blood achieved by the cooling means is within the range of 10° C. to 35° C.

13. The heat treatment apparatus of claim 2 wherein the temperature of the blood achieved by the second energy producing means is substantially normal body temperature within the range of 36° C. to 38° C.

14. The heat treatment apparatus of claim 1 wherein the blood has a rate of flow within the tubing of between 200 ml/minute and 500 ml/minute.

15. The heat treatment apparatus of claim 1 wherein the tubing has a substantially uniform cross section.

16. A method for treating a patient infected by a blood-borne virus, said method comprising the following steps: Step A: procure the heat treatment apparatus of claim 2; Step B: connect the inlet end of the tubing of the heat treatment apparatus to the patient; Step C: initiate the flow of blood from the patient to the heat treatment apparatus; Step D: subject the blood to heating within the first electromagnetic heating chamber of the heat treatment apparatus until a desired therapeutic temperature for the blood is achieved; Step E: maintain the blood at a constant temperature substantially equivalent to said desired therapeutic temperature within the second electromagnetic heating chamber of the heat treatment apparatus for a predetermined duration of time; Step F: subject the blood to cooling within the cooling chamber of the heat treatment apparatus until a desired cooling temperature for the blood is achieved, said cooling temperature being less than normal body temperature; Step G: subject the blood to heating within the third electromagnetic heating chamber of the heat treatment apparatus until the blood achieves normal body temperature; and Step H: return the blood through the outlet end of the tubing of the heat treatment apparatus to the patient by means of a cannula placed into the patient.

17. The method of claim 16 wherein the first electromagnetic heating chamber further comprises an inlet waveguide and an outlet waveguide; and the first energy producing means comprises a microwave transmitter coupled to the dwell chamber by way of a probe that projects into said chamber; whereby the blood is heated in Step D by the first energy producing means.

18. The method of claim 16 wherein the second energy producing means provides electromagnetic energy to said dwell chamber; the dwell chamber further comprises an inlet waveguide and an outlet waveguide; and the second energy producing means comprises a microwave transmitter coupled to the dwell chamber by way of a probe that projects into said chamber; whereby the blood is maintained at temperature in Step E by the second energy producing means.

19. The heat treatment apparatus of claim 1 wherein the dwell chamber is insulated and preheated to the selected elevated temperature sufficient for viral inactivation by the second energy producing means; whereby the blood is maintained at temperature in Step E by the second energy producing means.

20. The method of claim 16 wherein the blood is cooled in Step F by circulating a coolant through the cooling chamber.

21. The method of claim 16 wherein the second electromagnetic heating chamber further comprises an inlet waveguide and an outlet waveguide; and the third energy producing means comprises a microwave transmitter coupled to the dwell chamber by way of a probe that projects into said chamber; whereby the blood is heated in Step G by the third energy producing means.

22. The method of claim 16 wherein the temperature of the blood is radiometrically monitored in Steps D, E, and G.

23. The method of claim 16 wherein the temperature of the blood is radiometrically monitored in Step F.

Description

DESCRIPTION OF THE DRAWINGS

[0035] FIG. 1 is a schematic drawing of the device of the present invention.

[0036] FIG. 2 is a schematic drawing of the temperature profile of the blood as it passes through the various chambers of the apparatus of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

[0037] In accordance with the present invention, a continuously moving column of blood from a patient is rapidly heated in a microwave heating chamber 22 to a temperature high enough to provide heat destruction of virus activity in the blood. The blood is then flowed into a second chamber 22′ where the temperature achieved in the first chamber 22 is maintained for a predetermined amount of time to destroy the virus located in the blood. The blood is then moved into an in-line cooling chamber 34 where it is cooled to a non-destructive temperature. Preferably, the blood is cooled in the cooling chamber 34 below the selected delivery temperature and then routed to another in-line microwave heating chamber 22″ which heats the blood precisely to the desired delivery temperature (e.g., normal body temperature, or about 37° C.). In this way, the delivery temperature is approached from below for optimum accuracy.

[0038] The blood is flowed through the successive chambers through IV tubing 12 whose internal diameter is preferably quite small, e.g. 0.096 in., with respect to the wavelength of the microwave heating frequency used for heating the blood, thereby ensuring uniform heating of the blood which is in constant motion through the tubing. Preferably also, the tubing 12 is formed as a cartridge unit with a series of coils which may be positioned in the chambers present in the apparatus 20. Further in accordance with the present invention, means are provided for monitoring the temperature of the moving blood as it enters and leaves the various chambers utilizing non-invasive radiometry with detection occurring at microwave frequencies. This enables noninvasive measurements at depth to occur while the blood is in motion through the tubing 12. The measured differential temperatures are then used to determine the power level required for heating in the first and second heating chambers.

[0039] Using the in-line high temperature short time heating method described herein, a time/temperature profile may be produced in the moving column of blood to provide maximum heat destruction of virus activity while maintaining the functional constituency of the blood and product delivery at the proper delivery temperature.

[0040] Referring to FIG. 1, the blood is flowed through a cartridge unit shown generally at 10. The illustrated cartridge unit 10 includes dielectric tubing 12 with four tubing coils 12a, 12b, 12c, and 12d in series. The cartridge unit 10 may consist of four separate cartridges as depicted in FIG. 1 connected in series or it may be formed with a continuous length of tubing 12. In either event, the tubing 12 ends at the opposite ends of the series are provided with conventional connectors 14a and 14b to enable the cartridge unit 10 to be connected to a blood source and destination. In the preferred embodiment, connector 14a is connected to a patient through tubing to receive the patient's untreated blood in a manner as is known in the art, for example, as used in a hemodialysis device for extracting blood to be filtered, and connector 14b is coupled to a cannula inserted intravenously into the patient to receive the treated blood. Alternatively, connector 14a may be connected to a blood bag full of blood product and connector 14b may be coupled to an empty blood bag. If desired, a non-invasive flow regulator or paristoltic pump 16 may be provided to control the flow of blood through tubing 12. Preferably, the blood should flow through the tubing 12 at a substantially constant velocity. Moreover, the cross section of the tubing 12 must remain substantially uniform and fixed throughout the system to prevent turbulence, which could otherwise create air emboli.

[0041] Cartridge unit 10 is arranged to be used in conjunction with the heating/cooling apparatus shown generally at 20. Apparatus 20 includes a first microwave heating chamber 22 having an inlet waveguide 22a and an outlet waveguide 22b and an aperture for receiving the cartridge unit coil 12a. Microwave energy from a microwave transmitter 24 is coupled to heating chamber 22 by way of a standard launch or probe 26 that projects into chamber 22. Transmitter 24 may be controlled by a controller 28 having a control panel or keyboard 28a.

[0042] The temperature of the blood flowing through the tubing coil 12a in the first microwave heating chamber 22 is monitored radiometrically using a sensing probe (not shown) similar to probe 26 which is connected by a coaxial conductor 30 to a radiometer 28b in controller 28. Similar sensing probes 32a and 32b are present in the inlet and outlet waveguides 22a and 22b to monitor the temperature of the blood in tubing 12 entering and leaving chamber 22. The controller 28 responds to the temperature measurements provided by the various sensing probes to control the power of the microwave energy injected into the first microwave heating chamber 22 via launch probe 26 so as to raise the temperature of the blood flowing through the tubing coil 12a from an initial value T.sub.1 which is body temperature (about 37° C.), to a selected value T.sub.2 sufficient to inactivate viruses in the blood product, e.g., 77° C. The construction and operation of the first microwave heating chamber 22, with its probes, radiometric circuitry and controller, is described in detail in the above U.S. Pat. No. 5,073,167, which is incorporated herein by reference.

[0043] Apparatus 20 further includes a dwell chamber 22′ having an aperture for receiving the cartridge unit coil 12b. The dwell chamber 22′ may be substantially identical to the first microwave heating chamber 22. Accordingly, its components have the same numeric identifiers as the corresponding components in chamber 22. Note that the dwell chamber 22′ does not have a sensing probe 32a present in its inlet waveguide since the temperature of the blood in tubing 12 entering chamber 22′ is identical to the temperature of the blood in tubing 12 exiting chamber 22. Alternatively, the dwell chamber 22′ may be a preheated insulated chamber that uses means other than microwave heating to maintain its internal temperature at T.sub.2. The function of the dwell chamber 22′ is to controllably maintain the temperature of the column of blood flowing through tubing 12 after the blood has been heated in the first microwave heating chamber 22. When the blood leaves the dwell chamber 22′ it has the same temperature T.sub.2 as it had when entering the dwell chamber 22′. The flow rate of the blood and the length of tubing 12 within the dwell chamber 22′ determines the duration of time that the blood is exposed to the desired virus destroying temperature T.sub.2. This time may be a matter of only a fraction of a second to a few seconds.

[0044] Apparatus 20 also includes a cooling chamber 34 with an aperture for receiving the tubing coil 12c. Chamber 34 is provided with an inlet tube 34a and an outlet tube 34b by which a coolant 36 may be circulated through chamber 34 in order to rapidly, e.g., 1 second or less, cool the blood exiting dwell chamber 22′ to a non-destructive temperature T.sub.3 which may be somewhat below the ultimate delivery temperature, e.g., to 30° C.

[0045] The illustrated cartridge unit 10 has, in addition, a fourth tubing coil 12d which is adapted to be received in a fourth chamber 22″ of apparatus 20. Chamber 22″ is a second microwave heating chamber which may be substantially identical to the first microwave heating chamber 22. Accordingly, its components have the same numeric identifiers as the corresponding components in chamber 22. Its function is to controllably heat the column of blood flowing through tubing 12 after the blood has been cooled in cooling chamber 34. Using this 4-stage apparatus, the blood, having been overcooled in chamber 34, is heated in the second microwave heating chamber 22″ so that when the blood leaves apparatus 20 it has a desired delivery temperature T.sub.4 which should be the same as the initial temperature T.sub.1, that is, body temperature (about 37° C.). Allowing overshoot during cooling provides more rapid cooling and, in turn, better control of the duration of the short-line heating to reach the desired delivery temperature.

[0046] During operation of apparatus 20, the blood is flowed through cartridge unit 10 at a predetermined velocity. That velocity and the tubing 12 dimensions determine the residence time of the blood in each of the four chambers. Thus, by presetting those parameters and controlling the power of the microwave energy in chambers 22 and 22′, the time/temperature profile of the moving column of blood may be shaped to produce viral inactivation without undue cell damage.

[0047] The above described in-line cooling of the blood following heating allows the blood to be heated to temperatures previously assumed prohibited because, in the present apparatus 20, the heat exposure will be determined solely by the microwave power applied in chambers 22 and 22′ to the blood and the flow rate, bearing in mind that only a small amount of blood is heated at any given moment in the cartridge coils 12a and 12b in chambers 22 and 22′, respectively. Because such a small blood volume is involved, the warm-up time is very short and there is essentially no hold up time because the blood is always moving through the apparatus 20. Finally, due to the nature of the apparatus 20, the blood is subjected to uniform and closely controlled heating for the reasons stated above.

[0048] FIG. 2 illustrates the temperature profile of the blood as is passes through the various chambers 22,22′,34,22″ of the apparatus 20. Initially, before the blood enters the first microwave heating chamber 22, it is at normal body temperature (about 37° C.), having just been extracted from the patient. Upon entering the first microwave heating chamber 22, the blood is rapidly heated to the desired temperature for destroying virus activity. As shown in Figure two, this may be 77° C., but other temperatures may also be sufficient for destroying virus activity without overheating the blood, for example, temperatures within the range of 75° C. to 85° C. Once the blood has been heated to the desired temperature by the first microwave heating chamber 22, it passes into the dwell chamber 22′, where the desired temperature is maintained for a period of time. That period of time may be several seconds, enough for the heat to destroy the virus activity in the blood. Once the blood has been exposed to the desired temperature for the desired period of time, the blood passes into the cooling chamber 34, where the temperature of the blood is rapidly dropped to a temperature below the normal body temperature. As shown in Figure two, this may be 30° C., but other temperatures may also be sufficient, for example, temperatures within the range of 10° C. to 35° C. Finally, the blood passes into the second microwave heating chamber 22″, where it is brought up to normal body temperature, thus making it safe to reintroduce into the patient. Where the apparatus 20 is used to destroy viruses in stored blood product, the initial temperature and the final temperature may be other than normal body temperature; for example, the initial temperature of the blood may be 10° C. or so if the blood source was from a blood bag, and the final temperature may be significantly cooler than that if the blood destination is another blood bag slated for refrigeration.

[0049] The present invention also contemplates a method of treating a patient infected by a blood-borne virus. The method involves the following steps: [0050] Step A: Procure a device as described herein; [0051] Step B: Connect the inlet end of the tubing of the device to a patient infected by a blood-borne virus, in a manner well known in the art, for example, as is used for hemodialysis treatment of kidney disease; [0052] Step C: Initiate the flow of blood from the patient to the device; [0053] Step D: Subject the blood to rapid heating, maintenance of the elevated temperature, cooling, and then reheating to return to normal body temperature, by the means of operating the device as described herein; and [0054] Step E: Return the blood through the outlet end of the tubing of the device to the patient by means of a cannula placed into the patient.

[0055] It will thus be seen that the objects set forth above, among those made apparent from the preceding description, are efficiently attained. Also, certain changes may be made in carrying out the above method and in the construction set forth without departing from the scope of the invention. Therefore, it is intended that all matter contained in the above description or shown in the accompanying drawing shall be interpreted as illustrative and not in a limiting sense. It is also to be understood that the following claims are intended to cover all of the generic and specific features of the invention described herein.