Methods of analysis/separation

• US 5,653,859 A
• Filed: 11/20/1995
• Issued: 08/05/1997
• Est. Priority Date: 01/21/1993
• Status: Expired due to Fees

• Current Assignee: Scientific Generics Limited (Science Group Plc)
• Original Assignee: Scientific Generics Limited (Science Group Plc)
• Inventors: Huang, Ying, Pethig, Ronald, Pollard-Knight, Denise V., Wang, Xiao-Bo, MacGregor, Alastair R., Parton, Adrian
• Primary Examiner(s): Gorgos, Kathryn L.
• Assistant Examiner(s): STARSIAK, JOHN S
• Application Number:
  US08/495,447
• Time in Patent Office: 624 Days
• Field of Search: 204/600, 204/450, 204/451, 204/452, 204/453, 204/454, 204/455, 204/602, 204/601, 204/603, 204/604, 204/605
• US Class Current: 204/450
• CPC Class Codes: B03C 5/028 using travelling electric fields, i.e. travelling wave dielectrophoresis [TWD]
• CPC Class Codes: C12N 13/00 Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
• CPC Class Codes: C12N 15/1003 Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses therefor
• CPC Class Codes: G01N 33/5438 Electrodes
• CPC Class Codes: G01N 33/585 with a particulate label, e.g. coloured latex

Abstract

Particles are subjected to travelling wave field migration (TWFM) to migrate the particles over an array of microelectrodes. Altered particles are produced by treating original particles in such a way so as to alter their TWFM characteristics and the altered TWFM characteristics are employed for analysis and/or separation of the altered particles. The particles may be cells, bacteria, viruses, biomolecules or plastics microspheres. They may be altered by binding to a ligand such as a metal microparticle via a selective linking moiety such as an antibody/antigen or oligonucleic acid, or be physical or chemical treatments.

Claims

1. A method of analysis or separation comprising:

treating a plurality of original, particles to form a subplurality of altered particles from at least some of said plurality of original particles, said subplurality of altered particles having travelling wave field migration properties distinct from those of said plurality of original particles; and

producing translatory movement of said subplurality of altered particles and/or said plurality of original particles by travelling wave field migration using conditions such that said translatory movement of said subplurality of altered particle differs from said translatory movement of said plurality of original particles under the same conditions.

2. A method as claimed in claim 1, wherein:

said subplurality of altered particles are observable by use of a light-microscope.

3. A method as claimed in claim 1, wherein:

said subplurality of altered particles are too small to be observed by use of a light-microscope.

4. A method as claimed in any of claims 1, 2 or 3, wherein said subplurality of altered particles are formed from said plurality of original particles by a treatment comprising:

forming respective complexes between said subplurality of altered particles and a ligand.

5. A method as claimed in claim 4, wherein said respective complexes comprise:

a first linking moiety connecting said subplurality of altered particles and said ligand.

6. A method as claimed in claim 5, wherein said respective complexes further comprise:

a label connected to said ligand.

7. A method as claimed in claim 6, wherein:

said label is connected to said ligand via a second linking moiety.

8. A method as claimed in claim 1, wherein:

said plurality of original particles are treated so as to form said subplurality of altered particles by forming respective complexes between respective ones of said plurality of original particles and a ligand, said complexes having a dielectric property different from a dielectric property of said plurality of original particles, and said complexes are subjected to said travelling wave field migration with respect to a plurality of electrodes under conditions which displace said complexes away from said plurality of electrodes in a direction perpendicular to a direction of said travelling wave field migration and which produce migration dependent on an imaginary component of an induced dipole moment of said complexes.

9. A method as claimed in any one of claims 1 to 3, wherein:

said subplurality of altered particles are formed by a treatment which alters an intrinsic dielectric property of said plurality of original particles.

10. A method as claimed in any one of claim 1, 2, 3 or 8, wherein:

an effective wavelength of a travelling field is from 8 to 12 times a respective size of said subplurality of altered particles as measured transverse to a direction of movement under said travelling wave field migration.

11. A method as claimed in claim 5, wherein:

said first linking moiety is an immunological binding partner for said ligand carried by said particle or an oligonucleotide carried by said particle, said first linking moiety including a nucleotide sequence hybridizing with a nucleotide sequence present in said ligand.

12. A method as claimed in claim 7, wherein:

said second linking moiety is an immunological binding partner for said ligand carried by said label or an oligonucleotide carried by said label, said second linking moiety including a nucleotide sequence hybridizing with a nucleotide sequence present in said ligand.

13. A method of analysis or separation comprising:

treating a plurality of original particles to form a subplurality of altered particles from only some of said plurality of original particles, said subplurality of altered particles having travelling wave field migration properties distinct from travelling wave field migration properties of said plurality of original particles;

subjecting said plurality of original particles and said subplurality of altered particles to a row of parallel electrodes; and

producing translatory movement of said subplurality of altered particles and/or said plurality of original particles by travelling wave field migration by applying a travelling wave having a wavelength of about 8 to 12 times the size of said subplurality of altered particles and/or said plurality of original particles, to said row of parallel electrodes;

whereby said translatory movement of said subplurality of altered particles differs from said translatory movement of said plurality of original particles.

14. A method of analysis or separation comprising:

treating a plurality of original particles to form a subplurality of altered particles from only some of said plurality of original particles, said subplurality of altered particles having travelling wave field migration properties distinct from travelling wave field migration properties of said plurality of original particles;

subjecting said plurality of original particles and said subplurality of altered particles to a row of parallel electrodes; and

producing translatory movement of said subplurality of altered particles and/or said plurality of original particles by travelling wave field migration;

whereby said translatory movement of said subplurality of altered particles differs from said translatory movement of said plurality of original particles.