Millimeter wave flow cytometer

• US 5,144,224 A
• Filed: 04/01/1991
• Issued: 09/01/1992
• Est. Priority Date: 04/01/1991
• Status: Expired due to Fees

• Current Assignee: Lawrence E. Larsen
• Original Assignee: Lawrence E. Larsen
• Inventors: Larsen, Lawrence E.
• Primary Examiner(s): Wieder, Kenneth A.
• Assistant Examiner(s): Solis, Jose M.
• Application Number:
  US07/678,245
• Time in Patent Office: 519 Days
• Field of Search: 422/82.01, 422/82.02, 422/82.11, 209/571, 209/576, 324/71.4, 324/631, 324/632, 324/638, 324/639, 324/644, 324/642
• US Class Current: 324/71.4
• CPC Class Codes: G01N 15/1429 Signal processing
• CPC Class Codes: G01N 15/149 specially adapted for sorting particles, e.g. by their size or optical properties
• CPC Class Codes: G01N 22/00 Investigating or analysing materials by the use of microwaves or radio waves, i.e. electromagnetic waves with a wavelength of one millimetre or more G01N3/00 - G01N17/00, G01N24/00 take precedence

Abstract

A method and apparatus for millimeter wave flow cytometry of a cell stream hydrodynamically focused in a zone of interaction with a millimeter wave source and complex ratiometric receiver. The cell stream is characterized by complex power wave scattering parameters as a function of frequency, scattering angle and polarization. These parameters train a signal processor to sort specimen cells into one of a plurality of predetermined reference groups in accordance with a minimum number of normal cell types and functional states.

Claims

1. Apparatus for microwave flow cytometry, comprising:

(a) Means to isolate cells in a fluid and to hydrodynamically focus said cells single-file through an interaction zone of dimension comparable to a single cell;

(b) Generating means to generate, direct and closely couple incident microwave energy of predetermined frequency and polarization into said interaction zone;

(c) Receiving means to receive waves closely coupled to said interaction zone which have been affected by a cell in said interaction zone, with at least one of said generating or receiving means being rotated in at least a first plane;

(d) Measuring means to read values from said generating and receiving means, said measuring means evaluating complex S-parameters of each cell in said interaction zone as a function of frequency and as a function of the angular displacements of the rotated means in at least said first plane;

(e) Processing means receiving data from said measuring means, said data being used to classify cells in said interaction zone as member of a plurality of reference groups, said reference groups being predefined by prior tests upon known samples.

2. Apparatus as defined in claim 1, wherein the rotated means are mechanically rotated around an axis perpendicular to the axis or the cell motion in the interaction zone.

3. Apparatus as defined in claim 1, wherein the rotated means are mechanically rotated around an axis parallel to the axis of cell motion in the interaction zone.

4. Apparatus in claim 1, wherein said means being mechanically rotated is the receiving means.

5. Apparatus as in claim 1, wherein said prior tests of known samples are executed using a minimum number of both normal and pathological specimens in said fluid to characterize said reference groups.

6. Apparatus in claim 1, wherein the receiving means detects predominantly that portion of the incident wave reflected by each cell in the interaction zone.

7. Apparatus in claim 1, where the receiving means detects predominantly that portion of the incident wave transmitted by each cell in the interaction zone.

8. Apparatus as defined in claim 1, wherein said interaction zone is comprised of a flow channel and said generating or receiving means include transmission lines which are closely coupled to said interaction zone.

9. A method of cytometric evaluation of isolated cells, comprising the steps of:

(a) Isolating said cells in a fluid and hydrodynamically focusing said cells single-file in an interaction zone of dimensions comparable to a single cell;

(b) Generating and closely coupling incident microwave energy of a predetermined frequency into said interaction zone;

(c) Receiving closely coupled waves affected by each cell in the interaction zone while mechanically rotating at least one of the generating or receiving wave directions in at least one plane;

(d) Measuring at least one complex S-parameter based on readings from the generated and received values as a function of frequency and as a function of the angular position for said mechanical rotation;

(e) Processing data generated during said measuring step to classify each cell under analysis as a member of one of predetermined reference groups, said reference groups being previously defined by applying measuring steps to known calibrating samples of cells and fluids.