Methods and apparatus for electrosmear analysis
View Patent ↗Methods and apparatus for preparing a smear for cytopathology or other analysis. In a representative embodiment, cells of a sample are subjected to a dielectrophoretic force to segregate the cells into two or more zones of a surface. The particles are attached to the surface, thereby defining a “segregated smear.” The segregated smear is then fixed and stained for cytopathology analysis.
1. A method comprising:
subjecting particles of a sample to a dielectrophoretic force by simultaneously applying a swept frequency signal to a first set of electrodes and a fixed frequency signal to a second set of electrodes;
segregating the particles into two or more zones of a surface; and
attaching the particles to the surface; where the swept frequency signal falls from a maximum intensity to a minimum intensity along a length of a surface in a first direction, and the fixed frequency signal falls from a maximum intensity to a minimum intensity along the length of the surface in a second direction opposing the first direction.
2. The method of claim 1 , where the intensities vary linearly along the length of the surface.
3. The method of claim 1 , where the intensities vary non-linearly along the length of the surface.
4. The method of claim 1 , where the intensities are varied by varying a width of electrode buses with distance along a length of the surface.
5. The method of claim 1 , where the minimum intensity of the swept frequency or fixed frequency signal is non-zero.
6. The method of claim 1 , further comprising filtering the sample by subjecting particles of the sample to a flow, a cross flow, and a dielectrophoretic force that opposes a force associated with the cross flow.
7. The method of claim 6 , where the flow and cross flow are substantially perpendicular to one another.
8. The method of claim 6 , where the flow and cross flow are not perpendicular.
9. The method of claim 6 , where the dielectrophoretic force arises from the excitation of electrodes near a dielectric substrate having openings.
10. The method of claim 6 , where the dielectrophoretic force arises from current passing through an opening in a dielectric barrier.
11. The method of claim 1 , where attaching the particles into two or more zones comprises confining particles in a particular zone using a physical barrier.
12. The method of claim 1 , where segregating the particles comprises flow DEP-FFF.
13. The method of claim 1 , further comprising promoting growth of particles on the surface.
14. The method of claim 1 , further comprising automatically adjusting the swept frequency signal or fixed frequency signal as a function of conductivity of a particle suspending medium.
15. A method comprising:
subjecting particles of a sample to a dielectrophoretic force to segregate the particles into two or more zones of a surface by simultaneously applying a swept frequency signal applied to a first set of electrodes and a fixed frequency signal to a second set of electrodes;
attaching the particles to the surface, thereby defining a segregated smear; and
fixing or staining the segregated smear; where the swept frequency signal falls from a maximum intensity to a minimum intensity along a length of a surface in a first direction, and the fixed frequency signal falls from a maximum intensity to a minimum intensity along the length of the surface in a second direction opposing the first direction.
16. The method of claim 15 , comprising fixing and staining the segregated smear.
17. The method of claim 15 , the attaching comprising subjecting the particles to a dielectrophoretic force.
18. The method of claim 15 , the attaching comprising using an adhesive coupled to the surface.
19. The method of claim 15 , the attaching comprising allowing the particle to settle on the surface.
20. The method of claim 15 , the particles comprising cells.
21. The method of claim 15 , the smear comprising a pap smear.
22. The method of claim 15 , where subjecting particles to a dielectrophoretic force comprises subjecting the particles to a dielectrophoretic force arising from the simultaneous application of programmed voltage signals of different frequencies.
23. The method of claim 15 , where subjecting particles to a dielectrophoretic force comprises subjecting the particles to a dielectrophoretic force arising from the application of frequencies exhibiting one or more DEP-FFF and trapping phases.
24. The method of claim 15 , where subjecting particles to a dielectrophoretic force comprises subjecting the particles to dielectrophoretic forces generated by electrodes coupled to the surface.
25. The method of claim 24 , the electrodes comprising spiral electrodes.
26. The method of claim 15 , the two or more zones comprising concentric circular zones.
27. The method of claim 15 , the two or more zones comprising distinct bands of particles.
28. The method of claim 15 , where the intensities vary linearly along the length of the surface.
29. The method of claim 15 , where the intensities vary non-linearly along the length of the surface.
30. The method of claim 15 , where the intensities are varied by varying a width of electrode buses with distance along a length of the surface.
31. The method of claim 15 , where the minimum intensities of the swept frequency and fixed frequency signals are non-zero.
32. The method of claim 15 , further comprising automatically adjusting the swept frequency signal or fixed frequency signal as a function of conductivity of a particle suspending medium.
33. The method of claim 15 , further comprising filtering the sample by subjecting particles of the sample to a flow, a cross flow, and a dielectrophoretic force that opposes a force associated with the cross flow.
34. The method of claim 33 , where the flow and cross flow are substantially perpendicular to one another.
35. The method of claim 33 , where the flow and cross flow are not perpendicular.
36. The method of claim 33 , where the dielectrophoretic force arises from the excitation of electrodes near a dielectric substrate having openings.
37. The method of claim 33 , where the dielectrophoretic force arises from current passing through an opening in a dielectric barrier.
38. The method of claim 33 , where attaching the particles into two or more zones comprises use of a physical barrier to confine particles in a particular zone.
39. The method of claim 15 , where particles are segregated using flow DEP-FFF.
40. The method of claim 15 , further comprising promoting growth of particles on the surface.
41. An apparatus comprising:
a surface;
electrodes near the surface;
a first signal generator configured to apply a fixed frequency signal to a first electrode, the fixed frequency signal falling from a maximum intensity to a minimum intensity along a length of the surface in a first direction;
a second signal generator configured to apply a swept frequency signal to a second electrode, the swept frequency signal falling from a maximum intensity to a minimum intensity along the length of the surface in a second direction opposing the first direction, where the fixed frequency signal and the swept frequency signal are applied simultaneously; and
where applying the swept frequency signal in combination with the fixed frequency signal generates a dielectrophoretic force configured to segregate particles into two or more zones of the surface.
42. The apparatus of claim 41 , where the first and second signal generators are integral.
43. The apparatus of claim 41 , further comprising a filter coupled to the surface, the filter configured to subject particles of a sample to a flow, a cross flow, and a dielectrophoretic force that opposes a force associated with the cross flow.
44. The apparatus of claim 43 , the filter comprising electrodes near a dielectric substrate having openings.
45. The apparatus of claim 41 , further comprising a physical barrier near the surface configured to attach particles into two or more zones of the surface.