Use of vibrational spectroscopy for DNA content inspection
This disclosure concerns a cytometry system including a handling system that enables presentation of single cells to at least one laser source. The laser source is configured to deliver light to a cell within the cells in order to induce bond vibrations in the cellular DNA. The system further includes a detection facility that detects the signature of the bond vibrations, wherein the bond vibration signature is used to determine the folding or packing of the DNA.
1. A cytometry system, comprising:
a microfluidic channel with a measurement volume in which a cell in a sample fluid is introduced;
at least one laser source configured to emit at least one light at one or more wavelengths towards the cell resulting in a detectable change in the light;
wherein the at least one laser source is further configured to emit at a wavelength corresponding to the resonant absorption for the cell DNA;
a second laser source configured to emit at a second wavelength;
wherein a measured transmitted signal of the second wavelength is used to cancel out a background signal from analytes and/or from system artifacts;
at least one detector configured to measure the detectable change in the light; and
at least one processor configured to analyze the detectable change in the light and determine a characteristic of the cell.
2. The cytometry system of claim 1 , wherein the cell is not stained or dyed.
3. The cytometry system of claim 1 , wherein the cell is a sperm cell.
4. The cytometry system of claim 3 , wherein the sperm cell is an animal sperm cell.
5. The cytometry system of claim 4 , wherein the animal sperm cell is bovine, porcine, avian, or equine.
6. The cytometry system of claim 1 , wherein the at least one laser source is a quantum cascade laser (QCL).
7. The cytometry system of claim 1 , wherein the detectable change in the light is a change related to absorption, reflection, scatter, refraction, or a combination or a derivative thereof.
8. The cytometry system of claim 7 , wherein the change related to absorption of light is an induced bond vibration of the DNA within the cell.
9. The cytometry system of claim 1 , wherein the characteristic of the cell is gender.
10. The cytometry system of claim 1 , wherein the characteristic of the cell is a genetic difference or disorder.
11. The cytometry system of claim 1 , further comprising a selector configured to kill or damage the cell depending upon the characteristic of the cell.
12. A cytometry system, comprising:
a microfluidic channel with a measurement volume in which a cell in a sample fluid is introduced;
at least one laser source configured to emit at least one light at one or more wavelengths towards the cell resulting in a detectable change in the light;
at least one detector configured to measure the detectable change in the light; and
at least one processor configured to analyze the detectable change in the light and determine a characteristic of the cell;
a second light source;
a second detector;
wherein the second light source is configured to emit a second light at a wavelength that induces Mie scattering by the cell, the second detector detects light resulting from Mie scattering, and the detected light resulting from Mie scattering is used by the processor to identify the presence of a single cell in the measurement volume; and
wherein a measurement by the detector is gated in correspondence with the identified presence of a single cell in the measurement volume.
13. The cytometry system of claim 12 , wherein the processor is further configured to use detected light resulting from Mie scattering to identify a cell characteristic, wherein the cell characteristic comprises one or more of size, cell type, cell density, gender, cell orientation, and a combination thereof.
14. The cytometry system of claim 12 , wherein the second light source is one or more of a VIS, UV, and NIR laser source.
15. The cytometry system of claim 12 , further comprising a selector that selectively disables sperm cells based on the identified chromosome they are carrying and is controlled in correspondence to detected light resulting from Mie scattering.
16. The cytometry system of claim 15 , wherein the selector is a laser.
17. A method of cytometry comprising:
presenting a single cell to at least one laser source configured to deliver at least one light to the single cell in order to induce a detectable change in the light;
wherein the at least one laser source is further configured to emit at a wavelength corresponding to the resonant absorption for the cell DNA;
presenting the single cell to a second laser configured to emit at a second wavelength;
wherein a measured transmitted signal of the second wavelength is used to cancel out a background signal from analytes and/or from system artifacts;
detecting the detectable change in the light with at least one detector; and
processing the detectable change in the light to determine a characteristic of the single cell with at least one processor.
18. The method of claim 17 , wherein the single cell is not stained or dyed.
19. The method of claim 17 , wherein the single cell is a sperm cell.
20. The method of claim 19 , wherein the sperm cell is an animal sperm cell.
21. The method of claim 20 , wherein the animal sperm cell is bovine, porcine, avian, or equine.
22. The method of claim 17 , wherein the at least one laser source is a quantum cascade laser (QCL).
23. The method of claim 17 , wherein the detectable change in the light is a change related to absorption, reflection, scatter, refraction, or a combination or a derivative thereof.
24. The method of claim 23 , wherein the change related to absorption of light is an induced bond vibration of the DNA within the single cell.
25. The method of claim 17 , wherein the characteristic of the single cell is gender.
26. The method of claim 17 , wherein the characteristic of the single cell is a genetic difference or disorder.
27. The method of claim 17 , further comprising killing or damaging the single cell with a selector depending upon the characteristic of the single cell.
28. A method of cytometry comprising:
presenting a single cell to at least one laser source configured to deliver at least one light to the single cell in order to induce a detectable change in the light;
detecting the detectable change in the light with at least one detector;
processing the detectable change in the light to determine a characteristic of the single cell with at least one processor; and
presenting the single cell to a second light source and detecting the detectable change in light with a second detector, wherein the second light source is configured to emit a second light at a wavelength that induces Mie scattering by the cell, the second detector detects light resulting from Mie scattering, and the detected light resulting from Mie scattering is used by the processor to identify the presence of a single cell in the measurement volume; and wherein a measurement by the second detector is gated in correspondence with the identified presence of a single cell in a measurement volume.
29. The method of claim 28 , wherein the processor is further configured to use detected light resulting from Mie scattering to identify a cell characteristic, wherein the cell characteristic comprises one or more of size, cell type, cell density, gender, cell orientation, and a combination thereof.
30. The method of claim 28 wherein the second light source is one or more of a VIS, UV, and NIR laser source.
31. The method of claim 28 , further comprising selectively disabling sperm cells with a selector based on the identified chromosome they are carrying and is controlled in correspondence to detected light resulting from Mie scattering.
32. The method of claim 31 , wherein the selector is a laser.