X-OPTOGENETICS / U-OPTOGENETICS

• US 20160166852A1
• Filed: 12/16/2015
• Published: 06/16/2016
• Est. Priority Date: 12/16/2014
• Status: Active Grant

• Current Assignee: Rensselaer Polytechnic Institute
• Original Assignee: Rensselaer Polytechnic Institute
• Inventors: Getzin, Matthew, Berry, Rachel, Gjesteby, Lars, Wang, Ge
• Granted Patent: US 10,737,111 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 41/008 Two-Photon or Multi-Photon PDT, e.g. with upconverting dyes or photosensitisers
• CPC Class Codes: A61N 2005/0656 Chemical light sources
• CPC Class Codes: A61N 5/0622 Optical stimulation for exciting neural tissue

Abstract

Methods and systems for performing optogenetics using X-rays or ultrasound waves are provided. Visible-light-emitting nanophosphors can be provided to a sample, and X-ray stimulation can be used to stimulate the nanophosphors to emit visible light. Alternatively, ultrasonic waves can be provided to the sample to cause sonoluminescence, also resulting in emission of visible light, and this can be aided by the use of a chemiluminescent agent present in the sample. The emitted light can trigger changes in proteins that modulate membrane potentials in neuronal cells.

Claims

1. A method of performing optogenetics, comprising:

providing light-emitting particles to a sample; and

providing X-rays to the sample such that the X-rays cause the light-emitting particles to emit light, thereby changing the membrane potential of a neuron within the sample.

2. The method according to claim 1, wherein the light-emitting particles are visible-light-emitting nanophosphors, such that the nanophosphors emit light in the visible spectrum upon stimulation by the X-rays.

3. The method according to claim 1, wherein providing X-rays to the sample comprises providing X-rays with a carbon nanotube X-ray source.

4. The method according to claim 3, wherein the carbon nanotube X-ray source includes a carbon nanotube cathode emitting electrons that are focused onto an anode through at least one of a gate electrode and focusing electrode.

5. The method according to claim 1, wherein the sample is an animal brain.

6. The method according to claim 1, wherein providing X-rays to the sample comprises focusing the X-rays with a focusing element after they are provided by an X-ray source and before they reach the sample, wherein the focusing element is a poly-capillary lens, a Fresnel zone plate, or a grating.

7. The method according to claim 1, further comprising providing one or more type of rhodopsins to the sample before providing the X-rays, wherein the rhodopsins induce excitatory potentials in neurons of the sample,

wherein the neuron whose membrane potential is changed upon emission of light from the light-emitting particles is among the neurons in which excitatory potentials are induced by the rhodopsins,

wherein the method further comprises transfecting neurons of the sample with DNA encoding for a predetermined type of rhodopsin, prior to providing the rhodopsins,

wherein providing one or more type of rhodopsins comprises providing the predetermined type of rhodopsin, and

wherein the one or more type of rhodopsins comprises at least one of channelrhodopsin2 (ChR2), halorhodpsin (NphR), and archeorhodopsin (Arch).

8. The method according to claim 7, further comprising functionalizing the light-emitting particles to specifically bind to at least one type of rhodopsin of the one or more type of rhodopsins provided.

9. The method according to claim 1, wherein the light-emitting particles are coated with a surface coating that helps it pass the blood brain barrier of a human.

10. The method according to claim 1, wherein the light-emitting particles have a largest width, measured in any direction, of at least 150 nm.

11. A method of performing optogenetics, comprising:

providing chemiluminescent agents to a sample; and

providing ultrasonic waves to the sample causing a sonoluminescence effect within the sample and also causing the chemiluminescent agents to emit light, thereby changing the membrane potential of a neuron within the sample.

12. The method according to claim 11, wherein the chemiluminescent agents are fluoresceinyl Cypridina luminescent analog (FCLA) molecules.

13. The method according to any of claims 11, wherein the chemiluminescent agents emit light in the visible spectrum upon stimulation by the ultrasonic waves, and wherein providing ultrasonic waves to the sample comprises providing ultrasonic waves at a frequency on the order of kHz or MHz.

14. The method according to claim 11, wherein the sample is an animal brain.

15. The method according to claim 11, wherein the sample is a human brain, and

wherein the ultrasonic waves penetrate the skull of the human patient having the brain to a depth of from 0.3 cm to 3 cm.

16. The method according to claim 11, further comprising providing one or more type of rhodopsins to the sample before providing the ultrasonic waves, wherein the rhodopsins induce excitatory potentials in neurons of the sample,

wherein the neuron whose membrane potential is changed upon emission of light from the light-emitting particles is among the neurons in which excitatory potentials are induced by the rhodopsins,

wherein the method further comprises transfecting neurons of the sample with DNA encoding for a predetermined type of rhodopsin, prior to providing the rhodopsins,

wherein providing one or more type of rhodopsins comprises providing the predetermined type of rhodopsin, and

wherein the one or more type of rhodopsins comprises at least one of channelrhodopsin2 (ChR2), halorhodpsin (NphR), and archeorhodopsin (Arch).

17. The method according to claim 16, further comprising functionalizing the chemiluminescent agents to specifically bind to at least one type of rhodopsin of the one or more type of rhodopsins provided.

18. The method according to claim 11, wherein the chemiluminescent agents are coated with a surface coating that helps it pass the blood brain barrier of a human.

19. The method according to claim 11, wherein the ultrasonic waves are provided in pulses,

wherein each pulse has a duration of 5-100 milliseconds (ms).

20. A kit, comprising:

a) rhodopsins configured to induce excitatory potentials in neurons of a human brain; and

b) either the elements listed in i) or the elements listed in ii);

i) a carbon nanotube X-ray source configured to provide X-ray stimulation; and

visible-light-emitting nanophosphors configured to emit visible light upon stimulation from the carbon nanotube X-ray source;

or

ii) an ultrasound source configured to provide ultrasonic waves at a frequency on the order of kHz or MHz; and

visible-light-emitting chemiluminescent agents configured to emit visible light upon stimulation from the ultrasonic waves.