Method and apparatus for classifying biological cells

• US 4,150,360 A
• Filed: 12/14/1977
• Issued: 04/17/1979
• Est. Priority Date: 05/29/1975
• Status: Expired due to Term

• Current Assignee: Grumman Aerospace Corporation (Northrop Grumman Corporation)
• Original Assignee: Grumman Aerospace Corporation (Northrop Grumman Corporation)
• Inventors: Stone, Harvey, Pernick, Benjamin J., Wohlers, Martin R., Lisa, Joseph, Mendelsohn, Jay, Kopp, Richard E.
• Primary Examiner(s): Boudreau, Leo H.
• Application Number:
  US05/860,637
• Time in Patent Office: 489 Days
• Field of Search: 350/162 SF, 356/71, 356/39, 250/550, 128/2 B, 128/2 G, 340/146.3 P, 364/726, 364/416
• US Class Current: 382/133
• CPC Class Codes: G01N 15/0211 Investigating a scatter or diffraction pattern
• CPC Class Codes: G01N 2021/4716 Using a ring of sensors, or a combination of diaphragm and sensors; Annular sensor
• CPC Class Codes: G06V 10/88 Image or video recognition using optical means, e.g. reference filters, holographic masks, frequency domain filters or spatial domain filters

Abstract

A means of probing a biological cell sample with a optical source to determine the characteristics of the cell image by way of measuring parameters from its two dimensional Fourier transform. These techniques lead to a method of measuring discriminating parameters for cell classification.

Claims

1. Apparatus to investigate various morphological features of normal and cancerous cells comprising:

a source of coherent light;

a means to expand the light to cover a defined area;

a first means in the path of the expanded light to present the morphological features of cells thereto such that the coherent light is scattered by these features in the path of said light;

a first lens behind said first means to collect the scattered coherent light and project a diffraction pattern of said scattered coherent light to the focal point of said lens;

a second lens behind said first lens to collect the diffraction pattern at the focal point of said first lens, enlarge said diffraction pattern and project said diffraction pattern; and

an annular fiber optic disc of a plurality of fibers behind said second lens to collect said diffraction pattern with each of said fibers transmitting a portion of the energy of said diffraction pattern such that selecting outputs of certain fibers permit measuring the light intensity of such portion of the diffraction pattern corresponding to a predetermined radial distance and angular position from the center of the diffraction pattern.

2. Apparatus to investigate various structural or morphological features of normal and cancerous cells comprising:

a source of coherent light;

a means to enlarge the light;

a first means to present an image of a cell in the path of said light;

a lens behind said image to project a diffraction pattern of said image;

a second means behind said lens to enlarge said diffraction pattern and project same; and

a third means behind said second means to analyze said diffraction pattern quantitatively by providing signals of the light intensity representative of radial variation and angular variation of spatial frequency of optical energy off the center of the transform pattern, said third means including a first mask means for spatial distribution of optical energy of the diffraction pattern, said first mask means being adapted to translate along an axis of said aparatus and having an aperture for the transmission of the optical energy therethrough to thereby provide a scan of the radial variation of the spatial frequency of said optical energy; and

a second mask means for said spatial distribution of optical energy, said second mask being adapted to be interchanged with said first mask to translate along an axis of said apparatus and having an aperture for the transmission of the optical energy therethrough which is emanating from said magnifier in a conical pattern to thereby provide a scan of the angular variation of the spatial frequency of said optical energy.

3. Apparatus to investigate various structural or morphological features of cells to determine whether same have malignant characteristics, said apparatus comprising:

a source of collimated light;

a cell image means located to be exposed to said light such that said image will cause diffraction of the coherent light of said source of collimated light;

a convex lens located a predetermined distance behind said cell image means to collect the diffracted coherent light and transform same into a spatial distribution of optical energy in accordance with the expression, ##EQU27## where F(w_x, w_y) is the distribution of the Fourier transform in rectangular coordinates

f is the focal length

w_x is the transform x size scale

w_y is the transform y size scale

xo is a position coordinate in the input plane

yo is a position coordinate in the input plane perpendicular to the xo coordinate axis;

a means one focal length from said lens to magnify said optical energy that will provide a measurable pattern of its radial and angular variation; and

a means to select a measure of the pattern including a mask means for said spatial distribution of optical energy, said mask means being adapted to translate along an axis of said apparatus and having an aperture for the transmission of the optical energy therethrough to thereby provide a scan of the radial variation of the spatial frequency of said optical energy.

4. Apparatus to investigate various structural or morphological features of cells to determine whether same have malignant characteristics, said apparatus comprising:

a source of collimated light,

a cell image means located to be exposed to said light such that said image will cause diffraction of the coherent light of said source of collimated light;

a convex lens located a predetermined distance behind said cell image means to collect the diffracted coherent light and transform same into a spatial distribution of optical energy in accordance with the expression, ##EQU28## where F(w_x,w_y) is the distribution of the Fourier transform in rectangular coordinates

f is the focal length

w_x is the transform x size scale

w_y is the transform y size scale

xo is a position coordinate in the input plane

yo is a position coordinate in the input plane perpendicular to the xo coordinate axis;

a magnifier lens for said spatial distribution of optical energy located one focal length behind said convex lens that will provide pattern of optical energy having radial and angular variation; and

a means to provide signals from said pattern including a first mask means for said spatial distribution of optical energy, said first mask means being adapted to translate along an axis of said apparatus and having an aperture for the transmission of the optical energy therethrough which is emanating from said magnifier to thereby provide signals indicating the radial variation of the spatial frequency of said optical energy and another mask mounting means between said means to magnify and said photomultipler on the axis therebetween coincident with the axis of said source of collimated light, said another mask being also adaptable to translate along said axis and having an aperture to provide signals indicating angular variation of the spatial frequency of said optical energy as said mask mounting means is moved from one position to another position.

5. Apparatus to investigate various structural or morphological features of cells to determine whether same have malignant characteristics, said apparatus:

a source of collimated light;

an optical transducer cell image means located to be exposed to said light such that said image means located to be exposed to said light such that said image will cause diffraction of the coherent light of said source of collimated light;

a convex lens located a predetermined distance behind said cell image means to collect the diffracted coherent light and transform same into a spatial distribution of optical energy in accordance with the expression, ##EQU29## where F(w_x,w_y) is the distribution of the Fourier transform in rectangular coordinates

f is the focal length

w_x is the transform x size scale

w_y is the transform y size scale

xo is a position coordinate in the input plane

yo is a position coordinate in the input plane perpendicular to the xo coordinate axis;

a means to magnify said optical energy that will provide a mesurable pattern of its radial and angular variation; and

a fiber optic detector comprising a disc of fiber optic elements to receive said magnified optical energy, said detector having a disc of closely adjacent fiber optic elements that will transmit signals of the total light energy on the disc, said fiber optic elements providing signals of optical energy at a radial distance and angular position from the center of the transform plane.

6. Apparatus to investigate morphological features of normal and cancerous cells comprising:

a source of coherent light;

a means to enlarge the area of the source of coherent light;

a first means to present the morphological features of the cells in the direct path of said coherent light;

a convex lens behind said first means to project a diffraction pattern of the morphological features of the cells as impressed on said path of coherent light by said first means;

a second means behind said convex lens collecting the entire diffraction pattern on the path of said coherent light from the focal point of said convex lens, said second means also enlarging and projecting said entire diffraction pattern of the morphological features of the cells; and

a third means behind said second means, said third means having a face exposed to the entire, enlarged diffraction pattern, said face having means to produce signals from portions of the entire diffraction pattern to permit analyzation of said portions of said diffraction pattern by measuring the light intensity of said portions as a function of the radial distance from the center of the entire diffraction pattern.

7. The apparatus of claim 6 and further characterized by the third means also including means to provide signals from other portions of the entire diffraction pattern for the measuring of angular locations of the other portions.

8. The apparatus of claim 6 wherein the third means includes a solid state electronic sensor that will produce signals of radial and angular intensity of portions of the coherent light in the diffraction pattern appearing on semi-circular radial elements and finite length wedge elements forming said sensor.

9. The apparatus of claim 6 wherein the third means has fiber-optic elements arranged to be the face exposed to the entire, enlarged diffraction pattern that will permit the measurements to be made from signals from selected portions of fiber-optic elements.

10. The apparatus of claim 6 wherein the third means includes a first mask means for spatial distribution of optical energy of the diffraction pattern, said first mask means being adapted to translate along an axis of said apparatus and having an aperture for the transmission of the optical energy therethrough to thereby provide a scan of the radial variation of the spatial frequency of said optical energy;

and a second mask means for said spatial distribution of optical energy, said second mask being adapted to be interchanged with said first mask to translate along an axis of said apparatus and having an aperture for the transmission of the optical energy therethrough which is emanating from said magnifier in a conical pattern to thereby provide a scan of the angular variation of the spatial frequency of said optical energy.

11. The apparatus of claim 6 wherein said second means includes a magnifier lens to provide a spatial distribution of optical energy in said entire diffraction pattern, said magnifier lens being located one focal length behind said convex lens.