Methods and systems for assessing biological materials using optical and spectroscopic detection techniques

• US 20040052730A1
• Filed: 06/03/2003
• Published: 03/18/2004
• Est. Priority Date: 10/04/1995
• Status: Abandoned Application

• Current Assignee: Neurotherapeutics Pharma LLC
• Original Assignee: Cytoscan Sciences, LLC
• Inventors: Hochman, Daryl W.
• Application Number:
  US10/454,153
• Publication Number:
  US 20040052730A1
• Time in Patent Office: Days
• US Class Current: 424/9.2
• CPC Class Codes: C12Q 1/02 involving viable microorganisms
• CPC Class Codes: G01N 33/5005 involving human or animal cells immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

Optical detection techniques for the assessment of the physiological state, health and/or viability of biological materials are provided. Biological materials which may be examined using such techniques include cells, tissues, organs, subcellular components and intact animals. The inventive techniques may be employed in screening of potential diagnostic and/or therapeutic agents. One or more maps of data that correspond to the optical properties of a sample may be created and viewed.

Claims

1. A method for in vivo screening a candidate compound for activity as a diagnostic or therapeutic agent, comprising:

introducing a candidate compound to a sample of biological material in a subject;

acquiring at least two test data sets corresponding to one or more optical properties of at least one spatial location in the sample, wherein each test data set is acquired at different times over a time period;

creating at least one test map of the magnitude of at least some of the test data sets;

comparing the test map to a comparison map, wherein the comparison map corresponds to the magnitudes of one or more optical properties of a comparison sample having a predetermined physiological condition; and

assessing the activity of the candidate compound as a diagnostic or therapeutic agent based on the comparison between the test map and the comparison map.

2. The method of claim 1, wherein the comparison map corresponds to optical properties of a location in the sample different from the spatial location of the at least two test data sets.

3. The method of claim 1, wherein a series of test maps are created and further including displaying the series of test maps in succession to form a video of the test data sets over the time period.

4. The method of claim 1, wherein the time period is more than a day and wherein the assessing includes long term effects of therapeutic treatment with the agent.

5. The method of claim 4, wherein the long term effects are effects on a cell, tissue, organ system, or portion of the intact subject.

6. The method of claim 1, wherein each test data set represents a different spatial location on the subject and the test data sets are acquired by the subject moving with respect to an illumination source or the illumination source moving with respect to the subject.

7. The method of claim 1, wherein the subject is in a position with respect to an illumination source and an optical detector for acquiring the some of the test data sets, the subject is thereafter removed from the position, and the subject is returned to the original position for the acquiring of some other of the test data sets.

8. The method of claim 1, wherein the sample is located beneath an intact cranium of the subject and the assessing is for the use of the candidate compound in treating or diagnosing epilepsy, a migraine, a psychiatric disorder, or another nervous system disorder.

9. The method of claim 1, wherein the sample includes peripheral nerves and the assessment is for the use of the candidate compound in treating or diagnosing a pain.

10. The method of claim 1, wherein the assessment is for the use of the candidate compound in treating or diagnosing interictal or ictal activity in epilepsy models.

11. The method of claim 1, wherein the optical properties include light scattering, hemodynamic changes, such as vascularization, blood flow, blood oxygenation and blood volume, or a combination thereof, and the assessment is for the use of the candidate compound in treating or diagnosing eye disease.

12. The method of claim 1, wherein the sample includes epidermis nerves and the assessment is for the use of the candidate compound in treating or diagnosing diabetic neuropathy.

13. The method of claim 1, further including storing the test map in a database for drug screening, the database comprising data sets corresponding to one or more optical properties for a plurality of physiological conditions of biological samples in response to introduction with one or more agents.

14. The method of claim 1, wherein the acquiring of the test data sets is prior to introducing the candidate compound, during introducing the candidate compound, and after introducing the candidate compound.

16. The method of claim 11, wherein the optical properties represent an induced physiological condition and assessing includes evaluating the induced physiological condition.

17. The method of claim 11, wherein the induced physiological condition is due to genetic alteration, introduction of pathogens, contact with toxins, exposure to radiation or mechanical trauma.

18. The method of claim 11, wherein the physiological condition is due to a stroke.

19. The method of claim 14, wherein the assessing includes evaluating blood flow, blood oxygenation or blood volume of the subject.

20. The method of claim 14, wherein the contrast agents include light-absorbing indocyanine green or fluorescent dextran-bound fluorophores.

21. The method of claim 14, further including measuring of light scattering from cell swelling, stroke-induced apoptosis and hypoxia or tissue changes from ischemia and hypoxia.

22. The method of claim 11, wherein the physiological condition is the result of treatment of a subject suspected of having cancer.

23. The method of claim 18, wherein the cancer includes cancer of the breast, cervical, lung, skin or prostate.

24. The method of claim 18, wherein the comparison map includes empirical correlations to determine optical property changes as a function of tumor mass size, number of cancer cells or density of cancer cells.

25. The method of claim 18, wherein the optical properties reflect light scattering, blood volume, blood flow or blood oxygenation and the assessing is comprises determining whether the sample includes tumor tissue.

27. The method of claim 22, wherein the at least one optical detector includes a plurality of optical detectors and the method further including determining the number of photons leaving the sample at different angles per unit time to determine absorption of light.

28. The method of claim 22, wherein the at least one optical detector is a confocal microscope.

29. The method of claim 22, wherein the agent is assessed as a diagnostic or therapeutic agent for stroke and the optical properties reflect light scattering from cell swelling.

33. The device of claim 28, further including a physiological parameter reader to determine body temperature, pCO2, blood pressure, and/or level of anesthetic.

34. The device of claim 28, wherein a plurality of optical properties and wavelengths are measured.

15. A method for in vivo assessing the physiological condition of a subject, comprising:

administering a contrast agent to a biological sample in the subject;

acquiring at least two test data sets corresponding to one or more optical properties of resolved spatial locations within the sample following introduction of the contrast agent, wherein each test data set is acquired at different times over a time period;

creating a test map of the test data sets over the time period;

comparing the test map to a comparison map representing the magnitude of one or more optical properties of a comparison sample having a predetermined physiological condition over the time period; and

assessing the response of the sample to the administration of the contrast agent based on the comparison.

26. A method for in vivo screening a candidate compound for activity as a diagnostic or therapeutic agent, comprising:

illuminating a biological sample in a subject with electromagnetic radiation, by at least one illumination source;

aquiring test data corresponding to one or more optical properties of the sample, by at least one optical detector;

comparing the test data to comparison data corresponding to one or more optical properties of a comparison sample having predetermined viabilitiy properties; and

assessing the activity of the candidate compound as a diagnostic or therapeutic agent based on the comparison.

31. The database of claim 26, wherein the biological samples includes a subcellular level, cells, tissues, organ systems or a portiono of an intact subject.

36. The method of claim 31, wherein the sample includes a subcellular sample, at least one cell, a tissue, an organ system or a portion of an intact subject.

30. A database for drug screening comprising data sets corresponding to one or more optical properties for a plurality of physiological conditions of biological samples in response to introduction with one or more compounds.

32. A device for high-throughput screening of a candidate compound for activity as a diagnostic or therapeutic agent, the device comprising:

at least one illumination source to illuminate a biological sample in a subject with electromagnetic radiation;

at least one optical detector to aquiring test data corresponding to one or more optical properties of the sample;

a movable stage to support the subject and move the sample into a position relative to the at least one illumination source and at least one optical detector; and

a computer to determine the position for measuring the sample and to compare the test data to comparison data corresponding to one or more optical properties of a comparison sample having predetermined viabilitiy properties.

35. A computer assisted method for screening a candidate compound for activity as a diagnostic or therapeutic agent, comprising:

instructing a database to access at least one stored data set corresponding to one or more optical properties of a comparison sample having a predetermined physiological condition;

entering at least one criterion for the stored data set;

retrieving all data sets matching the criterion;

comparing the retrieved data set(s) to at least one test data set, wherein the at least one test data set corresponds to one or more optical properties of at least one spatial location in a sample of biological material in a subject, the at least one test data set being obtained by introducing a candidate compound to the sample and acquiring the at least one test data sets; and

assessing the activity of the candidate compound as a diagnostic or therapeutic agent based on the comparison between the at least one test data set and the retrieved data set(s).