Method for identifying optical contrast enhancing agents

• US 6,834,238 B1
• Filed: 06/04/1999
• Issued: 12/21/2004
• Est. Priority Date: 06/08/1998
• Status: Expired due to Fees

• Current Assignee: Neurotherapeutics Pharma LLC
• Original Assignee: Cytoscan Sciences, LLC
• Inventors: Hochman, Daryl W.
• Primary Examiner(s): MORAN, MARJORIE A
• Application Number:
  US09/326,244
• Time in Patent Office: 2,027 Days
• Field of Search: 702/21, 702/19, 702/38, 600/407, 600/310, 600/458, 600/477, 382/128, 382/133, 382/130, 435/29, 435/366, 356/300, 356/402, 700/32, 128/922, 128/923
• US Class Current: 702/21
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/635 having a heterocyclic ring, e.g. sulfadiazine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

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 and subcellular components. The inventive techniques may be employed in high throughput screening of potential diagnostic and/or therapeutic agents.

Claims

1. A method for identifying optical contrast enhancing agents useful for enhancing the sensitivity of optical detection of a biological material comprising:

maintaining at least one sample population of the biological material in one of the following systems;

a cell culture system;

a tissue culture system;

an organ culture system; and

an intact organism;

exposing the at least one sample population to a candidate optical contrast enhancing agent;

illuminating the at least one sample population with electromagnetic radiation (emr);

acquiring test data relating to one or more optical properties of the sample population subsequent to exposure to the candidate optical contrast enhancing agent;

comparing the test data acquired to comparison data relating to the one or more optical properties of the sample population, the comparison data being derived from empirically determined controls, whereby changes in the one or more optical properties reflected in the test data compared to the comparison data represent the optical contrast enhancing activity of said agent in said sample population; and

based on the comparison data, determining if the optical contrast enhancing agent is useful for distinguishing pathological cells or tissue.

3. The method of claim 1 or 2, additionally comprising maintaining multiple sample populations in an in vitro culture system.

4. The method according to claim 1, or 2, wherein the biological material is a viable, intact organism.

6. The method according to claim 1 or 5, wherein the biological material is an organ culture system.

9. The method of claim 1, 5, 7 or 2, additionally comprising acquiring multiple test data sets relating to one or more optical properties of the sample population at multiple, selected spatial locations in the sample population.

10. The method of claim 1, 5, 7 or 2, additionally comprising exposing the sample population to a physiological challenge prior to acquiring the test data.

11. The method of claim 10, wherein the physiological challenge is selected from the group consisting of:

exposure to a test agent, a test condition, a drug, a hormone, a biological agent, a toxin, an infectious agent, radiation, chemotherapy, deprivation of a metabolite or nutrient, electrical stimulation, inflammatory agent, and oncogen.

12. The method of claim 1, 5, 7 or 2, additionally comprising acquiring control data relating to the one or more optical properties of the sample population prior to exposing the sample population to a candidate optical contrast enhancing agent.

13. The method of claim 12, additionally comprising comparing the test data to the control data to assess changes in the one or more optical properties of the sample population representing activity of the candidate optical contrast enhancing agent.

14. The method of claim 1, 5, 7 or 2, wherein the test data acquired relates to one or more optical properties selected from the group consisting of:

reflection, refraction, diffraction, absorption, scattering, birefringence, refractive index and Kerr effect.

2. A method for identifying optical contrast enhancing agents useful for enhancing the sensitivity of optical detection of a biological material comprising:

maintaining at least one sample population of the biological material in one of the following systems;

a cell culture system;

a tissue culture system;

an organ culture system; and

an intact organism;

exposing the at least one sample population to a candidate optical contrast enhancing agent;

illuminating the at least one sample population with electromagnetic radiation (emr) having a wavelength of from 700-2500 nm;

acquiring test data relating to one or more optical properties of the sample population subsequent to exposure to the candidate optical contrast enhancing agent;

comparing the test data acquired to comparison data relating to the one or more optical properties of the sample population, whereby changes in the one or more optical properties reflected in the test data compared to the comparison data represent the optical contrast enhancing activity of said agent in said sample population; and

based on the comparison data, determining if the optical contrast enhancing agent is useful for distinguishing pathological cells or tissue.

8. The method of claim 5, 7 or 2, wherein the comparison data is derived from empirically determined controls.

5. A method for identifying optical contrast enhancing agents useful for enhancing the sensitivity of optical detection of a biological material comprising:

maintaining multiple sample populations in an in vitro culture system;

exposing the sample populations to a candidate optical contrast enhancing agent;

illuminating the sample populations with electromagnetic radiation (emr);

acquiring test data relating to one or more optical properties of the sample populations subsequent to exposure to the candidate optical contrast enhancing agent;

comparing the test data acquired to comparison data relating to the one or more optical properties of the sample populations whereby changes in the one or more optical properties reflected in the test data compared to the comparison data represent the optical contrast enhancing activity of said agent is said sample populations and

based on the comparison data, determining if the optical contrast enhancing agent is useful for distinguishing pathological cells or tissue.

7. A method for identifying optical contrast enhancing agents useful for enhancing the sensitivity of optical detection of a biological material comprising:

maintaining at least one sample population of the biological material in a viable intact organism;

exposing the at least one sample population to a candidate optical contrast enhancing agent;

illuminating the at least one sample population with electromagnetic radiation (emr);

acquiring test data relating to one or more optical properties of the sample population subsequent to exposure to the candidate optical contrast enhancing agent;

comparing the test data acquired to comparison data relating to the one or more optical properties of the sample population, whereby changes in the one or more optical properties reflected in the test data compared to the comparison data represent the optical contrast enhancing activity of said agent in said sample population; and

based on the comparison data, determining if the optical contrast enhancing magnet is useful for distinguishing pathological cells or tissue.