Apparatus and method for electrophysiological testing

• US 7,011,939 B2
• Filed: 02/23/2001
• Issued: 03/14/2006
• Est. Priority Date: 03/22/2000
• Status: Expired due to Term

• Current Assignee: Abbvie Incorporated
• Original Assignee: Abbott Laboratories Incorporated
• Inventors: Briggs, Clark A., Bojan, Peter, Bertrand, Daniel C., McKenna, David G., Trumbull, Jonathan D., Pan, Jeffrey Y., Blanchard, David P., Maslana, Eugene S., Nemcek, Thomas A.
• Primary Examiner(s): Beisner, Willaim H.
• Application Number:
  US09/790,871
• Publication Number:
  US 20010029320A1
• Time in Patent Office: 1,845 Days
• Field of Search: 435/29, 435/32, 435/33, 435/30, 435/187.1, 435/286.2, 435/286.4, 435/286.5, 435/287.3, 435/288.3, 435/6, 435/4, 435/3, 435/287.4
• US Class Current: 435/3
• CPC Class Codes: G01N 35/028 having reaction cells in the form of microtitration plates

Abstract

A method and apparatus for running a plurality of tests concurrently to obtain data relating to the electrophysiological properties of receptors and channels in biological membranes of test subjects, such as, for example, Xenopus oocytes. The invention further provides software for controlling, acquiring, and recording data relating to electrophysiological properties of receptors and channels in biological membranes of test subjects, such as, for example, oocytes. This invention increases the throughput rate for experiments and assays employing receptors and ion channels expressed in biological membranes of test subjects, such as, for example, oocytes. In the case of an oocyte, these receptors and channels may be natively expressed (endogenous), may be placed into the oocyte (exogenous), or may be expressed from other RNA or DNA previously placed into the oocyte (exogenous).

The invention provides a means for a sole researcher to operate a plurality of electrophysiological test stations in the time and space conventionally required by a single electrophysiological test station. The invention automates these stations and provides a means for a sole individual to perform large sets of experiments that would be physically and mentally exhausting in the absence of this invention. In addition, this invention provides efficient database and data analysis software integrated with the data acquisition software, thereby increasing the user'"'"'s data-handling productivity to keep pace with the augmented data generation capacity.

Claims

1. A method for running a plurality of tests to obtain electrophysiological data, the method comprising the steps of:

(a) providing a plurality of recording stations, each of said recording stations capable of containing at least one test subject;

(b) introducing at least one test subject into a first one of said plurality of recording stations;

(c) introducing at least one test subject into a second one of said plurality of recording stations;

(d) assessing the viability of said at least one test subject in said first one of said plurality of recording stations;

(e) assessing the viability of said at least one test subject in said second one of said plurality of recording stations;

(f) introducing at least one test material into at least one of said plurality of recording stations that contains a viable test subject as determined by the assessment made in steps (d) and (e), wherein a movable applicator introduces said at least one test material of step (f) directly into at least one of said plurality of recording stations;

(g) replacing said at least one test subject in said first one of said plurality of recording stations if said at least one test subject in said first one of said plurality of recording stations fails to respond adequately to a control or if the electrophysiological data of said at least one test subject in said first one of said plurality of recording stations exceeds a user-defined set point;

(h) replacing said at least one test subject in said second one of said plurality of recording stations if said at least one test subject in said second one of said plurality of recording stations fails to respond adequately to a control or if the electrophysiological data of said at least one test subject in said second one of said plurality of recording stations exceeds a user-defined set point; and

(i) collecting said electrophysiological data from each of said plurality of tests, wherein the steps (b), (c), (d), (e), (f), (g), (h), and (i) are carried out without substantial intervention by a human operator, further including the step of disabling said first one of said recording stations if said first one of said recording stations has a higher than expected number of failures, the expected number of failures being defined by the user.

2. The method of claim 1, wherein each of said recording stations comprises:

(a) a holder for said test subject;

(b) a means for measuring the electrical response of said test subject to said at least one test material.

3. The method of claim 2, wherein each of said recording stations further includes a controller for controlling the electrical environment of said test subject.

4. The method of claim 1, wherein said at least one test material is introduced by means of a fluid stream.

5. The method of claim 1, wherein said movable applicator is automated.

6. The method of claim 1, wherein said plurality of tests is run with the aid of a control system.

7. The method of claim 6, wherein said control system is capable of carrying out at least one of:

(a) scheduling;

(b) recording data;

(c) altering at least one parameter during a run;

(d) storing data;

(e) analyzing data.

8. The method of claim 7, wherein said at least one parameter is selected from the group consisting of flow rate of test material, start time of test material application, stop time of test material application, duration of introduction of test material, recovery period of test subject, name of control material, concentration of control material, control repetition interval, digital sampling rate, temperature of said test subject, and electrophysiological holding potential.

9. The method of claim 7, wherein said control system identifies the condition of said test subject.

10. The method of claim 1, wherein said at least one test subject is introduced by means of a movable applicator.

11. The method of claim 10, wherein said movable applicator is automated.

12. The method of claim 1, further including the step of removing said at least one test subject from each of said plurality of recording stations.

13. The method of claim 1, wherein said plurality of tests is run in sequence.

14. The method of claim 1, wherein said plurality of tests is run concurrently.

15. A method for running a plurality of tests to obtain electrophysiological data, the method comprising the steps of:

(a) providing a plurality of recording stations, each of said recording stations capable of containing at least one test subject;

(b) introducing at least one test subject into a first one of said plurality of recording stations;

(c) introducing at least one test subject into a second one of said plurality of recording stations;

(d) assessing the viability of said at least one test subject in said first one of said plurality of recording stations;

(e) assessing the viability of said at least one test subject in said second one of said plurality of recording stations;

(f) introducing at least one test material into at least one of said plurality of recording stations that contains a viable test subject as determined by the assessment made in steps (d) and (e), wherein a movable applicator introduces said at least one test material of step (f) directly into at least one of said plurality of recording stations;

(g) replacing said at least one test subject in said first one of said plurality of recording stations if said at least one test subject in said first one of said plurality of recording stations fails to respond adequately to a control or if the electrophysiological data of said at least one test subject in said first one of said plurality of recording stations exceeds a user-defined set point;

(h) replacing said at least one test subject in said second one of said plurality of recording stations if said at least one test subject in said second one of said plurality of recording stations fails to respond adequately to a control or if the electrophysiological data of said at least one test subject in said second one of said plurality of recording stations exceeds a user-defined set point; and

(i) collecting said electrophysiological data from each of said plurality of tests, wherein the steps (b), (c), (d), (e), (f), (g), (h), and (i) are carried out without substantial intervention by a human operator, further including the step of disabling said second one of said recording stations if said second one of said recording stations has a higher than expected number of failures, the expected number of failures being defined by the user.

16. The method of claim 15, wherein each of said recording stations comprises:

(a) a holder for said test subject;

(b) a means for measuring the electrical response of said test subject to said at least one test material.

17. The method of claim 16, wherein each of said recording stations further includes a controller for controlling the electrical environment of said test subject.

18. The method of claim 15, wherein said at least one test material is introduced by means of a fluid stream.

19. The method of claim 15, wherein said movable applicator is automated.

20. The method of claim 15, wherein said plurality of tests is run with the aid of a control system.

21. The method of claim 20, wherein said control system is capable of carrying out at least one of:

(a) scheduling;

(b) recording data;

(c) altering at least one parameter during a run;

(d) storing data;

(e) analyzing data.

22. The method of claim 21, wherein said at least one parameter is selected from the group consisting of flow rate of test material, start time of test material application, stop time of test material application, duration of introduction of test material, recovery period of test subject, name of control material, concentration of control material, control repetition interval, digital sampling rate, temperature of said test subject, and electrophysiological holding potential.

23. The method of claim 21, wherein said control system identifies the condition of said test subject.

24. The method of claim 15, wherein said at least one test subject is introduced by means of a movable applicator.

25. The method of claim 24, wherein said movable applicator is automated.

26. The method of claim 15, further including the step of removing said at least one test subject from each of said plurality of recording stations.

27. The method of claim 15, wherein said plurality of tests is run in sequence.

28. The method of claim 15, wherein said plurality of tests is run concurrently.