Methods for detecting bioactive compounds
View Patent ↗Methods of detecting bioactive compounds include exposing compounds to one or more classes of chromatophores and measuring or sensing associated changes in one or more of the chromatophores. Representative methods permit identification and quantification of neurotransmitters, toxins, hormones, and chemical warfare agents with or without prior knowledge of the content of a sample. In some examples, chromatophores based on Betta fish are used. Cytosensor apparatus using such chromatophores include means for exposing chromatophores to a sample and optical detection systems for assessing changes in chromatophore optical properties. Compounds can be identified or quantified based on a red-green-blue or hue saturation-value representations of transmitted or reflected light or based on other characterizations of transmitted or reflected light.
1. A method for detecting a bioactive compound or organism, comprising:
providing at least one bead comprising chromatophores in a first optical state;
commingling the bioactive compound or organism with the chromatophores; and
detecting an optical change in at least one chromatophore from the first optical state to a second optical state in response to the bioactive compound or organism.
2. The method of claim 1 , wherein the chromatophores are fish chromatophores and an optical change in the at least one chromatophore is selected from a group consisting of pigment aggregation, pigment dispersion, and hue changes.
3. The method of claim 1 , wherein the bioactive compound is selected from a group consisting of neurotransmitters, adrenergic agonists, adrenergic antagonists, seratonergic antagonists, hormones, cytoskeletal inhibitors, cAMP Signal transduction modulators, calcium ion signal transduction modulators, membrane voltage regulators, neurotoxins, protein kinase modulators, caustic irritants, heavy metals, polyaromatic hydrocarbons, organo phosphate nerve agents, psychogenic agents, antihistamines, enzyme inhibitors, algal toxins, bacteria, and bacterial protein toxins.
4. The method of claim 1 , wherein the organism includes a bacteria, fungus, virus, plant, or animal.
5. The method of claim 1 , wherein the chromatophores are Betta chromatophores.
6. The method according to claim 1 , comprising:
exposing a first type of chromatophore to a sample potentially comprising a bioactive compound or organism;
exposing a second type of chromatophore to a sample potentially comprising a bioactive compound or organism; and
identifying at least one class of compounds by comparing an optical appearance of the first type of chromatophore and the second type of chromatophore prior to exposure to the bioactive compound or organism and after exposure to the bioactive compound.
7. The method of claim 6 , wherein the first and second types of chromatophore are melanophores and erythrophores, respectively.
8. The method of claim 7 , wherein the chromatophores are fish chromatophores.
9. The method of claim 1 useful for identifying a calcium channel blocker, comprising:
exposing an erythrophore chromatophore and a melanophore chromatophore to a known calcium channel blocker, thereby producing a known response to the calcium channel blocker;
exposing the erythrophore chromatophore to a sample potentially comprising a calcium channel blocker;
exposing the melanophore chromatophore to the sample; and
determining that the sample includes a calcium channel blocker based on an erythrophore dispersion response and no melanophore response.
10. The method of claim 1 where the chromatophores have a first color prior to commingling the bioactive compound or organism with the chromatophores and a second color after commingling the bioactive compound or organism with the chromatophores, the method further comprising detecting a color change from the first color to the second color of at least one chromatophore.
11. The method of claim 10 , further comprising determining if a test sample includes a compound selected from a group consisting of neurotransmitters, hormones, intracellular signal transduction agents, pharmaceutically active agents, toxic agents, agricultural chemicals, chemical toxins, biological toxins, microbes, and animal cells based on the color change.
12. The method of claim 1 further comprising:
selecting a bacteria that produces a bacterial-induced response on the at least one chromatophore;
exposing a combination of the at least one chromatophore and the bacteria to the bioactive compound;
exposing the combination to a control compound selected based on a control response produced on the chromatophore;
determining a measured response of the chromatophore to the exposure of the combination to the control compound; and
evaluating the bioactive compound based on a difference in the measured response, the bacterial-induced response, and the control response.
13. The method of claim 12 , wherein the control compound is norepinephrine.
14. The method according to claim 1 where the at least one bead is formed from glass or polymeric material.
15. The method according to claim 14 where the polymeric material is alginate.
16. A method for detecting a bioactive compound or organism, comprising:
providing at least one bead comprising Betta chromatophores in a first optical state;
exposing the Betta chromatophores in the first optical state to the bioactive compound or organism; and
detecting an optical change in at least one Betta chromatophore from the first optical state to a second optical state in response to the bioactive compound or organism.
17. The method according to claim 16 where exposing comprises exposing two or more classes of Betta splendens chromatophores to the bioactive compound or organism.
18. The method according to claim 17 where the Betta splendens chromatophores are isolated chromatophores.
19. The method according to claim 16 and further comprising exposing the bioactive compound or organism to chromatophores in addition to the Betta chromatophores.
20. A method for detecting a bioactive compound or organism, comprising:
providing at least one bead comprising isolated chromatophores;
exposing the isolated chromatophores to a bioactive compound or organism; and
quantifying a scalar optical change in at least one chromatophore in response to the bioactive compound.
21. A method for detecting a bioactive compound or organism, comprising:
providing beads comprising two or more types of isolated, primary Betta splendens chromatophores;
commingling the bioactive compound or organism with the chromatophores; and
detecting a scalar optical change in at least one chromatophore in response to the bioactive compound or organism.
22. The method according to claim 21 where detecting the scalar optical change comprises computer aided detection.