Method of and apparatus for determining a property of a sample

• US 5,691,633 A
• Filed: 04/07/1995
• Issued: 11/25/1997
• Est. Priority Date: 07/24/1992
• Status: Expired due to Fees

• Current Assignee: British Technology Group Ltd.
• Original Assignee: British Technology Group Ltd.
• Inventors: Liu, Ying, Tweedie, Richard John, Belch, Jill Janette Freda, Abel, Eric William
• Primary Examiner(s): O'Shea, Sandra L.
• Assistant Examiner(s): Phillips, Roger
• Application Number:
  US08/374,659
• Time in Patent Office: 963 Days
• Field of Search: 324/71.1, 324/71.2, 324/767, 324/719, 324/425, 324/263, 324/529, 324/71.5, 324/464, 324/461, 324/452, 324/453, 324/71.4, 324/71.3
• US Class Current: 324/71.1
• CPC Class Codes: G01N 15/12 by observing changes in resistance or impedance across apertures when traversed by individual particles, e.g. by using the Coulter principle
• CPC Class Codes: G01N 15/13 Details pertaining to apertures
• CPC Class Codes: G01N 15/132 Circuits

Abstract

An apparatus and method for determining a property of a sample, derived from a response obtained from the sample after an electrical pulse has been applied to it. Blood cells are subjected to an electrical pulse, a response is obtained using data retrieval means and a Fourier Transform is applied to the response. As the pulse applied is of very short duration (ideally a Dirac pulse) the Fourier transform yields information across a very broad bandwidth, typically several MHz, and accordingly a wide range of frequency response data is obtained. Certain cellular defects can be deduced from the transformed data. A detector is provided to detect precisely the presence of a cell as it passes through a particular region of an oriface. This is then used to trigger the pulse at a precisely controlled instant. This reduces the effect of random dispersion and can be adapted to ignore noise peaks which inevitably occur. The invention may be operated continuously and provides information across a bandwidth which is wider than was previously possible.

Claims

1. A method of determining a distinctive property of a sample, comprising steps of:

applying an electrical pulse to an electrode arrangement across said sample in an electrolyte, said sample being transportable relative to said electrode arrangement, and said electrical pulse having an ON duty cycle of less than 20%;

detecting a response to said electrical pulse;

applying a transform to said detected response; and

determining said distinctive property of said sample from said transform of said detected response.

2. A method of determining a distinctive property according to claim 1, wherein:

said distinctive property is an electrical property.

3. A method of determining a distinctive property according to claim 1 or 2, wherein:

said sample includes a cell.

4. A method of determining a distinctive property according to claim 1, wherein:

said electrode arrangement applies said electrical pulse and senses said response.

5. A method of determining a distinctive property according to claim 4, comprising a further step of:

detecting a position of said sample relative to said electrode arrangement;

said electrical pulse being applied in dependence on said detected position of said sample.

6. A method of determining a distinctive property according to claim 4 or 5, wherein:

said sample is a particle;

an orifice is provided through which said particle is transported; and

said electrode arrangement is located so as to enable said electrical pulse to be applied to said particle as said particle is transported through said orifice.

7. A method of determining a distinctive property according to claim 6, wherein:

a first duration of said electrical pulse is less than 20% of a second duration of said transportation of said particle through said orifice.

8. A method of determining a distinctive property according to claim 1, wherein said step of detecting said response includes steps of:

determining a first response to said electrical pulse in an absence of said sample; and

determining a second response to said electrical pulse in a presence of said sample;

said second response to said electrical pulse includes a first component due to said sample itself and a second component due to influences external to said sample, said first component being determined from a difference between said second response and said first response.

21. A method of determining a distinctive property according to claim 8, wherein:

said second component due to influences external to said sample is indicative of a characteristic of said orifice.

22. A method of determining a distinctive property according to claim 6, wherein:

a first duration of said electrical pulse is less than 10% of a second duration of said transportation of said particle through said orifice.

37. A method of determining a distinctive property of a sample according to claim 1, wherein:

said applied electrical pulse is a square pulse.

38. A method of determining a distinctive property of a sample according to claim 1, wherein:

said electrical pulse is 2 μ

s to 5 μ

s wide.

39. A method of determining a distinctive property of a sample according to claim 1, wherein:

said electrical pulse is 2 μ

s wide.

40. A method of determining a distinctive property of a sample according to claim 1, wherein:

said electrical pulse is 0.5 to 5 mA in amplitude.

41. A method of determining a distinctive property of a sample according to claim 1, wherein:

said electrical pulse is 3 mA in amplitude.

42. A method of determining a distinctive property of a sample according to claim 1, wherein:

said electrical pulse has a rise time and a fall time on the order of 20 to 40 nS.

43. A method of determining a distinctive property of a sample according to claim 1, wherein:

said electrical pulse is triggered only when said sample is in a middle of an orifice.

47. A method of determining a distinctive property according to claim 1, wherein:

said electrical pulse has an ON duty cycle of less than 10%.

9. Apparatus for determining a distinctive property of a sample, comprising:

means for applying an electrical pulse to said sample, said electrical pulse having an ON duty cycle of less than 20%;

means for detecting a response to said electrical pulse;

means for applying a transform to said detected response; and

means for determining said distinctive property of said sample from said transform of said detected response;

said sample being transportable in an electrolyte relative to said means for applying said electrical pulse.

10. Apparatus for determining a distinctive property of a sample according to claim 9, wherein:

said distinctive property is an electrical property.

11. Apparatus for determining a distinctive property of a sample according to claim 9, further including:

an electrode arrangement by which said electrical pulse is applied and said response is detected.

12. Apparatus for determining a distinctive property of a sample according to claim 11, further comprising:

means for detecting a position of said sample relative to said electrode arrangement;

said means for applying said electrical pulse being arranged to apply said electrical pulse in dependence on said detected position of said sample.

13. Apparatus for determining a distinctive property of a sample according to claim 11 or 12, said apparatus further comprising:

an orifice through which said particle is transportable; and

said electrode arrangement being located so as to enable said electrical pulse to be applied to said particle as said particle is transported through said orifice.

14. Apparatus for determining a distinctive property of a sample according to claim 13, wherein:

a first duration of said electrical pulse is less than 20% of a second duration of said transportation of said particle through said orifice.

15. Apparatus for determining a distinctive property of a sample according to claim 9, wherein said means for detecting said response to said electrical pulse comprises:

means for determining a first response to said electrical pulse in an absence of said sample, for determining a second response to said electrical pulse in a presence of said sample, and for determining a component of said second response due to said sample from a difference between said second response and said first response.

16. Apparatus for determining a distinctive property of a sample according to claim 15, wherein said means for determining includes:

a reference test device; and

a live test device;

said means for determining being arranged to determine said first response and said second response simultaneously in said reference test device and said live test device, respectively.

17. Apparatus for determining a distinctive property of a sample according to claim 9, further comprising:

material having a low dielectric constant being interposed between an inner two electrodes of said electrode arrangement.

18. Apparatus for determining a distinctive property of a sample according to claim 17, wherein:

a ratio of a thickness of said material to a distance between said inner two electrodes is greater than 25%.

19. Apparatus for determining a distinctive property of a sample according to claim 9, wherein:

a ratio of an area of one of an electrode pair of said electrode arrangement to a separation of electrodes of said electrode pair is less than 500.

20. Apparatus for determining a distinctive property of a sample according to claim 13, wherein said means for detecting said response of said electrical pulse includes:

two electrodes mounted at opposite ends of said orifice.

23. Apparatus for determining a distinctive property of a sample according to claim 13, wherein:

a first duration of said electrical pulse is less than 10% of a second duration of said transportation of said particle through said orifice.

24. Apparatus for determining a distinctive property of a sample according to claim 17, wherein:

a ratio of a thickness of said material to a distance between said inner two electrodes is greater than 50%.

25. Apparatus for determining a distinctive property of a sample according to claim 9, wherein:

a ratio of an area of one of an electrode pair of said electrode arrangement to a separation of electrodes of said electrode pair is less than 200.

26. Apparatus for determining a distinctive property of a sample according to claim 9, wherein:

a ratio of an area of one of an electrode pair of said electrode arrangement to a separation of electrodes of said electrode pair is less than 100.

27. Apparatus for determining a distinctive property of a sample according to claim 9, further comprising:

two electrodes with a dielectric substance therebetween, said two electrodes being in contact with said sample.

28. Apparatus for determining a distinctive property of a sample according to claim 9, wherein:

said means for applying an electrical pulse includes two outer electrodes with a dielectric substance therebetween; and

said means for detecting said response to said electrical pulse includes two inner electrodes.

29. Apparatus for determining a distinctive property of a sample according to claim 28, wherein:

said two inner electrodes form a portion of an orifice through which said sample is transportable in said electrolyte.

30. Apparatus for determining a distinctive property of a sample according to claim 9, wherein:

said electrical pulse applied by said means for applying is a square pulse.

31. Apparatus for determining a distinctive property of a sample according to claim 9, wherein:

said electrical pulse is 2 μ

s to 5 μ

s wide.

32. Apparatus for determining a distinctive property of a sample according to claim 9, wherein:

said electrical pulse is 2 μ

s wide.

33. Apparatus for determining a distinctive property of a sample according to claim 9, wherein:

said electrical pulse is 0.5 to 5 mA in amplitude.

34. Apparatus for determining a distinctive property of a sample according to claim 9, wherein:

said electrical pulse is 3 mA in amplitude.

35. Apparatus for determining a distinctive property of a sample according to claim 9, wherein:

said electrical pulse has a rise time and a fall time on the order of 20 to 40 nS.

36. Apparatus for determining a distinctive property of a sample according to claim 9, wherein:

said reference test device and said live test device are arranged into a bridge configuration.

48. Apparatus for determining a distinctive property of a sample according to claim 9, wherein:

said electrical pulse has an ON duty cycle of less than 10%.

44. A method of determining a presence of an abnormality in a sample, comprising steps of:

applying an electrical pulse to a sample through an electrode pair, said sample being transportable relative to said electrode arrangement, and said electrical pulse having an ON duty cycle of less than 20%;

detecting a response to said electrical pulse;

applying a transform to said detected response; and

determining said presence of said abnormality in said sample based on said transform of said detected response.

49. A method of determining a presence of an abnormality in a sample according to claim 44, wherein:

said electrical pulse has an ON duty cycle of less than 10%.

45. Apparatus for determining a presence of an abnormality in a sample, said apparatus comprising:

an electrical pulse generator for applying an electrical pulse having an ON duty cycle of less than 20% to said sample as it is suspended in an electrolyte and transported through an orifice;

a detector for detecting a response to said electrical pulse;

a processor to apply a transform to said detected response, and to determine said presence of said abnormality in said sample based on said transform of said detected response.

46. Apparatus for determining a presence of an abnormality in a sample according to claim 45, wherein:

said electrical pulse generator is triggered to apply said electrical pulse to said sample only when said sample is in an optimal position in said orifice.

50. Apparatus for determining a presence of an abnormality in a sample according to claim 45, wherein:

said electrical pulse has an ON duty cycle of less than 10%.