Apparatus for delivering a controlled dosage of a chemical substance

• US 4,629,686 A
• Filed: 06/14/1982
• Issued: 12/16/1986
• Est. Priority Date: 02/19/1982
• Status: Expired due to Term

• Current Assignee: Biovest International, Inc.
• Original Assignee: Endotronics Incorporated
• Inventors: Gruenberg, Micheal L.
• Primary Examiner(s): Naff, David M.
• Assistant Examiner(s): Deck, Randall E.
• Application Number:
  US06/388,136
• Time in Patent Office: 1,646 Days
• Field of Search: 222/52, 222/56, 364/413, 364/414, 364/415, 364/416, 435/1, 435/289, 435/291, 435/813, 435/283, 435/284, 435/287, 604/50, 604/66
• US Class Current: 435/286.5
• CPC Class Codes: A01N 1/0247 for perfusion, i.e. for circulating fluid through organs, blood vessels or other living parts
• CPC Class Codes: C12M 33/07 Dosage or metering devices therefore
• CPC Class Codes: C12M 35/08 Chemical, biochemical or biological means, e.g. plasma jet, co-culture
• CPC Class Codes: C12M 41/26 of pH
• CPC Class Codes: C12M 41/34 of gas
• CPC Class Codes: C12M 41/48 Automatic or computerized control automatic analysis G01N35/00

Abstract

An apparatus is disclosed which delivers a dosage of a chemical substance preferably to a biological tissue in such a controlled manner that the concentration affecting the biological tissue is known at each and every point in time. The apparatus includes a plurality of vessels with each vessel containing a different concentration of the chemical substance. A valve has a plurality of inlets and a single outlet wherein each inlet is connected to a corresponding vessel. The biological tissue is preferably held within a chamber for treatment with the chemical substance. A pump positioned preferably between the valve and the biological tissue provides a transport force for delivering the chemical substance to the tissue. The valve and the pump are controlled by a computer control system which determines which inlet of the valve is fluidly connected to the outlet for providing a preselected concentration of the chemical substance to the tissue such that the concentration of the chemical substance affecting the tissue is controlled at each and every point in time.

Claims

1. An apparatus for delivering a controlled dosage of a chemical substance to a cell culture, the apparatus comprising:

a plurality of vessels, each vessel containing a different known concentration of the same chemical substance;

valving means having a plurality of inlet and a single outlet and having means for selectively connecting in fluid communication a preselected inlet to the single outlet;

first conduit means for fluidly connecting each vessel to a corresponding inlet of the valving means;

cell culture means for containing a cell culture, said cell culture means being in fluid connection with the outlet of the valving means and having an initial concentration of the chemical substance;

second conduit means for fluidly connecting the single outlet of the valving means to the cell culture means;

means for providing a transport force to the chemical substance in a flow controlled manner for delivering the chemical substance to the cell culture means and being in fluid communication with the outlet of the valving means and the cell culture means; and

control means for controlling the valving means having means for providing input signals and means for providing signals indicative of a desired program of administration such that a preselected inlet is fluidly connected to the outlet for presenting a first preselected known concentration of the chemical substance to the cell culture means, and for controlling the means for providing a transport force to the chemical substance to effect a selected rate of delivery, including means for controlling the concentration of the chemical substance in the cell culture means according to the program of administration corresponding to the equation ##EQU18## wherein t=integration time interval

V=volume of fluid within the cell culture means in which the chemical substance is being delivered

R=the rate of delivery of the chemical substance to the cell culture means

C_i =the initial concentration level of the chemical substance in the integration time interval within the cell culture means

C.sub.(t) =the final concentration of the chemical substance in the integration time interval within the cell culture means

C_s =the concentration of the chemical substance being delivered in the integration time interval from the vessels into the cell culture means

wherein the means for controlling the concentration selects values of R/V and C_s such that the concentration change between C_i and C.sub.(t) is linear and the control means for controlling the valving means selectively switches among the vessels to choose C_s for each integration time interval in response to the desired program of administration.

2. The apparatus of claim 1 wherein the cell culture means is a culture chamber having an inlet fluidly connected to the second conduit means and an outlet.

3. The apparatus of claim 2 and further including means for collecting the chemical substance connected to the outlet of the culture chamber.

4. The apparatus of claim 3 and further including analyzer means for analyzing the chemical substance after being collected by the means for collecting.

5. The apparatus of claim 3 and further including means for sterily collecting the chemical substance in the means for collecting.

6. The apparatus of claim 2 and further including gas delivery means for delivering gas to the chemical substance in the plurality of vessels.

7. The apparatus of claim 6 wherein the gas delivery means includes diffusion means for diffusing the gas within each vessel.

8. The apparatus of claim 1 wherein the control means includes a programmed digital computer system.

9. The apparatus of claim 1 wherein the valving means includes means for maintaining a sterile seal to all inlets not connected to the outlet.

10. The apparatus of claim 1 wherein the valving means has twelve inlets.

11. The apparatus of claim 1 wherein the means for providing a transport force is a pump.

12. The apparatus of claim 11 wherein the pump is a peristaltic pump.

13. The apparatus of claim 12 wherein the peristaltic pump has a flow delivery rate accuracy of ±

0.01 milliliters in any time interval.

14. An apparatus comprising:

a plurality of different source concentrations of a chemical substance;

valving means having a plurality of inlets and a single outlet for fluidly connectng a preselected inlet to the single outlet and having means for selectively connecting in fluid communication a selected single inlet with the outlet;

first conduit means for fluidly connecting each source concentration to a corresponding inlet of the valving means;

a chamber for receiving the chemical substance in a controlled manner and environment being in fluid communication with the outlet of the valving means and having an initial concentration of the chemical substance;

second conduit means for fluidly connecting the single outlet of the valving means to the chamber;

means for providing a transport force to the chemical substance in a flow controlled manner for delivering the chemical substance to the chamber being in fluid communication with the outlet of the valving means; and

control means for controlling the valving means having means for providing input signals and means for providing signals indicative of a desired program of administration such that a preselected inlet is fluidly connected to the outlet for presenting a first preselected known concentration of the chemical substance to the chamber, and for controlling the means for providing a transport force to the chemical substance to effect a selected rate of delivery, including means for controlling the concentration of the chemical substance in the chamber according to the program of administration corresponding to the equation ##EQU19## wherein t=the integration time interval

V=volume of fluid within the chamber in which the chemical substance is being delivered

R=the rate of delivery of the chemical substance to the chamber

C_i =the initial concentration level of the chemical substance in the integration time interval within the chamber

C.sub.(t) =the final concentration of the chemical substance in the integration time interval within the chamber

C_s =the concentration of the chemical substance being delivered in the integration time interval from the source concentration into the chamber

wherein the means for controlling the concentration selects values of R/V and C_s such that the concentration change between C_i and C.sub.(t) is linear and the control means for controlling the valving means selectively switches among the source concentrations to choose C_s for each integration time interval in response to the desired program of administration.

15. The apparatus of claim 14 wherein the control means includes a computer control system.

16. The apparatus of claim 15 wherein the computer control system controls the environment in the chamber.

17. The apparatus of claim 14 and further comprising at least one sensing input for providing signals to the control means.

18. The apparatus of claim 17 wherein the sensing input is a pH sensor for sensing pH within the chamber.

20. The apparatus of claim 14 and further comprising operator input means for inputting concentration parameters to the control means.

19. The apparatus of claim 19 wherein the sensing input is an oxygen sensor for sensing oxygen content within the chamber.