Real time sampling, monitoring and exposure control of test animals

• US 8,116,985 B1
• Filed: 03/19/2007
• Issued: 02/14/2012
• Est. Priority Date: 03/17/2006
• Status: Active Grant

• Current Assignee: Battelle Memorial Institute
• Original Assignee: Battelle Memorial Institute
• Inventors: Bresler, Herbert S., Brooker, Michael J., Johnson, Jerry D., Graves, Steven W., Hong, Seongwon, Gritz, R. Mark
• Primary Examiner(s): Lin, Jerry
• Application Number:
  US11/687,938
• Time in Patent Office: 1,793 Days
• Field of Search: 702/19
• US Class Current: 702/19
• CPC Class Codes: A61B 2503/40 Animals
• CPC Class Codes: A61B 2503/42 for laboratory research
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: A61B 5/0215 by means inserted into the body catheters A61M25/00
• CPC Class Codes: A61B 5/024 Detecting, measuring or recording pulse rate or heart rate A61B5/0205, A61B5/021 take precedence
• CPC Class Codes: A61B 5/145 Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissuemeasuring of blood pressure or blood flow A61B5/02; non-radiation detecting or locating of foreign bodies in blood A61B5/06
• CPC Class Codes: A61B 5/15003 for venous or arterial blood
• CPC Class Codes: A61B 5/150229 Pumps for assisting the blood sampling
• CPC Class Codes: A61B 5/150366 Blood collection bags, e.g. connected to the patient by a catheter comprising means for removing a small sample of collected blood from the bag collection bags as such A61J1/05, A61M1/0209
• CPC Class Codes: A61B 5/150992 Blood sampling from a fluid line external to a patient, such as a catheter line, combined with an infusion line; blood sampling from indwelling needle sets, e.g. sealable ports, luer couplings, valves tubing connectors and couplings A61M39/00
• CPC Class Codes: A61B 5/153 Devices specially adapted for taking samples of venous or arterial blood, e.g. with syringes
• CPC Class Codes: A61B 5/155 Devices specially adapted for continuous or multiple sampling, e.g. at predetermined intervals devices loaded with multiple lancets simultaneously A61B5/15146
• CPC Class Codes: A61B 5/157 Devices characterised by integrated means for measuring characteristics of blood
• CPC Class Codes: A61B 5/4848 Monitoring or testing the effects of treatment, e.g. of medication

Abstract

An automated blood or bodily fluid sampling machine for collecting, measuring and monitoring real time samples from test animals during dosing of the animals, automatically provides real-time adjustment of dosing during testing. Such automated blood or bodily fluid sampling is performed in tandem with implanted physiological monitoring devices to monitor biological and physiological parameters in restrained or freely-moving test animals. The real-time feedback provides for dosing adjustment within testing protocols.

Claims

1. A method for automatic exposure control of a single test animal based on real-time data collected from the single test animal, comprising the steps of:

a) providing a single test animal having at least one implanted catheter, and optionally, at least one implanted monitoring device;

b) simultaneously;

i) exposing the single test animal of step a) to at least one test condition, and

ii) capturing multiple measurements of samples, over a period of time, from the same single test animal to provide real-time data related to the status of the same single test animal under test with no human-animal contact during testing, wherein the real-time data comprises same single test animal generated responses, over time, to the test condition, and wherein the test condition comprises one or more of a biological parameter, physiological parameter, or combinations thereof;

c) comparing the real-time data of step b) from the same single test animal to a database of prior generated data from the same single test animal; and

d) automatically controlling the conditions of the test to which the same single test animal is exposed to produce further real-time data by automatically adjusting the test conditions in response to the same single test animal'"'"'s response to the test and to the real-time data being captured from the same single test animal.

2. The method of claim 1 wherein the step of capturing the real-time data comprises

automatically drawing multiple samples of blood or other fluid via the catheter from the same single test animal, absent human-animal contact during testing;

and

analyzing the samples to determine the biological parameter of the same single test animal.

3. The method of claim 2 wherein the step of analyzing the biological parameter comprises determining the presence, level, change in level and/or other value of a blood constituent, drug, toxin, other test material, biochemical, biomarker, protein, cell, macrophage, virus, bacteria, DNA, RNA, mRNA, gene sequence, or other target analyte.

4. The method of claim 2 wherein

the step of capturing real-time data from the same single test animal further comprises automatically transferring the multiple samples to a sample analysis device, absent human-animal contact during testing;

and

the step of analyzing further comprises preparing the multiple samples for analysis, absent human-animal contact during testing.

5. The method of claim 2 wherein the step exposing the same single test animal to the test condition, and the step of capturing multiple measurements of samples, are performed using the separate catheters.

6. The method of claim 1 wherein the step of comparing comprises:

determining the biological uptake;

evaluating toxicokinetic effect;

assessing toxicodynamics of a drug, toxin or other test material;

or combinations thereof.

7. The method of claim 1 wherein the same single test animal also has an a monitoring device implanted therein, wherein the step of capturing multiple measurements of samples, over a period of time, from the same single test animal to provide real-time data of the physiological parameter comprises measuring, using the implanted monitoring device, one or more of:

motion, temperature, ocular pressure, interperitoneal pressure, EEG readings, EMG, EKG, blood pressure, venous pressure, left ventricle pressure;

pleural pressure, ECG-P, PR, QRS and interval measurements, QT interval, GP, or combinations thereof.

8. The method of claim 1 wherein the step of automatically controlling comprises automatically adjusting conditions of the test, and responsively producing multiple measurements of real-time data from the same single test animal at a value relative to one or more reference values, absent human-animal contact during testing.

9. The method of claim 8 where the step of responsively producing multiple measurements of real-time data comprises maintaining the value of the biological parameter at a desired level over a period of time.

10. The method of claim 9, wherein the biological parameter is the level or change in level of a drug, toxin or test material in a test animal.

11. The method of claim 1 wherein the step of exposing the same single test animal to the test condition comprises at least one of delivering at least one drug, toxin or other test material to the same single test animal by inhalation, intravenous administration, injection, whole body exposure, ingestion, installation, implantation, stomach tube, administration through a bodily orifice, or combinations thereof.

12. The method of claim 1 wherein the method further comprises repeating the steps of exposing, capturing, comparing and controlling using the same single test animal.

13. The method of claim 12 further comprising the step of selecting or excluding the same single test animal for breeding in accordance with the presence, level or other value of one or more of the biological parameter, physiological parameter or combinations thereof.

14. The method of claim 12 wherein the method further comprises the step of providing automatic feedback of the real-time data to the data base for generating a database including the real-time data.

15. The method of claim 12 wherein after the step of repeating exposing, capturing, comparing and automatically controlling is performed in accordance with a test protocol, the method further comprises:

repeating the steps of capturing and comparing; and

monitoring the health status of the same single test animal.

16. The method of claim 1 wherein the physiological monitoring device comprises an implanted monitoring device having a wireless transmitter.

17. The method of claim 1 further including generating a feedback signal to control one or more of:

the step of exposing the same single test animal to the test condition, and the step of capturing multiple measurements of samples from the same single test animal.

18. The method of claim 17, wherein the same single test animal is exposed to the test condition at a threshold of toxicity on a continuing basis.