Automated microscope for blood cell analysis

• US 8,067,245 B2
• Filed: 07/24/2006
• Issued: 11/29/2011
• Est. Priority Date: 07/24/2006
• Status: Active Grant

• Current Assignee: Medica (B C Partners Holdings Limited)
• Original Assignee: Medica (B C Partners Holdings Limited)
• Inventors: Jones, Ronald, Sheng, Amy P., van Ryper, William John, Cote, Tyler, Small, Steven I., Ma, Ivan Hee Yiu
• Primary Examiner(s): Nagpaul; Jyoti
• Application Number:
  US11/492,372
• Publication Number:
  US 20080020128A1
• Time in Patent Office: 1,954 Days
• Field of Search: 436/174, 436/180, 422 63- 67, 422 99-100, 422/563, 359/391
• US Class Current: 436/174
• CPC Class Codes: G01N 1/312 for samples mounted on planar substrates
• CPC Class Codes: G01N 2001/317 spraying liquids onto surfaces
• CPC Class Codes: G01N 35/0099 comprising robots or similar manipulators robots per se B25J
• CPC Class Codes: G02B 21/26 Stages; Adjusting means therefor
• CPC Class Codes: G02B 21/34 Microscope slides, e.g. mounting specimens on microscope slides
• CPC Class Codes: G02B 21/362 Mechanical details, e.g. mountings for the camera or image sensor, housings G02B21/364 takes precedence
• CPC Class Codes: Y10T 436/25 including sample preparation
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

An apparatus and method of automated blood cell analysis uses technologies from other systems to create a new, robust, improved type of automated microscope, which uses electronic motors and a closed loop control system to minimize ambient factors, such as jarring and temperature changes. Pre-stained blood smear slides are first coated with a thin film of oil and are loaded into a carousel from which they can individually be analyzed. The slides are moved under a low magnification microscope; an optimal area of examination is determined; a focal plane map is calculated for that area, and the positions of white blood cell candidates are computed. The slide is then moved under a high power microscope where a refined focal plane map is computed and the individual white blood cell candidates are imaged. The cells are preclassified and the images are made available for analysis by the technician. Additionally, samples of red blood cells, equivalent to what the technician would do manually, are imaged and presented to the technician for evaluation. The technician may make notes on those cells, both red and white blood cells and archive them.

Claims

1. An apparatus for analyzing stained blood cells on a microscope slide which comprises:

(a) a computer comprising;

i. a processor;

ii. random access memory;

iii. a monitor in communication with the computer; and

iv. an input device in communication with the computer;

(b) a base having a flat surface lying in the X-Y plane;

(c) a gripper to acquire and transport the microscope slides and which serves as a microscope stage;

the gripper being constrained to move in the X-Y plane

(d) a motor to move the gripper in the X direction;

(e) a motor to move the gripper in the Y direction;

(f) a microscope tower fixed with respect to the base

(g) two microscopes with optical axes lying parallel to the Z direction, wherein the microscopes have upper parts attached to the microscope tower and lower parts comprising objectives of different powers and aligned to the optical axes, the lower parts being constrained to move in the z direction along their optical axes,

(h) wherein a first of the two upper parts is aligned with a first of the objectives along a first of the optical axes,

(i) wherein a second of the two upper parts is aligned with a second of the objectives along a second of the optical axes,

(i) wherein the motors allow the gripper to move a cell located on the slide under either the first or second aligned microscope objectives;

(k) at least one focusing actuator for moving the two microscope objectives in the Z direction; and

(l) a light source to illuminate the microscope slides.

2. An apparatus as in claim 1, in which the computer has a system processor comprising at least 2.4 GHz.

3. An apparatus as in claim 1, in which the computer random access memory comprises at least 512 MB.

4. An apparatus as in claim 1, in which the computer input device comprises at least one of a keyboard, mouse, roller ball, or touch screen.

5. An apparatus as in claim 1, further including a carousel with multiple slots for the microscope slides and wherein the gripper is operative to acquire the microscope slides from the carousel.

6. An apparatus as in claim 1, further including a reader to capture an identifier on an end of each microscope slide.

7. An apparatus as in claim 6, wherein the reader is an electronic camera capable of interpreting a bar code.

8. An apparatus as in claim 1, in which the stage motors comprise linear induction motors, which are optically encoded to a strip fixed to the base.

9. An apparatus as in claim 8, in which the stage motors move reliably and accurately to within about 0.5 microns.

10. An apparatus as in claim 1, in which the gripper to acquire and transport microscope slides comprises:

a. a lever having a forked end;

b. the forked end comprising spaced apart furcations;

c. each furcation is pinned pivotally at two points to a cam, which is controlled by a servo motor to turn the cam to open and close the furcations; and

d. the furcations are bridged with a spring to keep them under tension.

11. An apparatus as in claim 10, in which one of the furcations has sufficient free play, approximately 0.05 inches, to accommodate microscope slides of differing widths.

12. An apparatus as in claim 1, in which the light source includes an LED source and fiber optics, and wherein light conducted by the fiber optics from the LED source is shaped by light condensers.

13. An apparatus as in claim 12, in which the fiber optics are looped to eliminate anisotropy from the LED light source.

14. An apparatus as in claim 1, in which the focusing actuator for moving the objectives in the Z axis is a voice coil, a coil portion of which is attached to the microscope tower, and the magnetic portion of which is attached to an objective carriage for the objectives and wherein the coil is under positive tension from at least one extension spring, and optically encoded to a strip fixed to the base.

15. An apparatus as in claim 14, in which the voice coil is capable of focusing reliably to within about 20 nm resolution.

16. The apparatus as in claim 1, further including means to establish an initial focus of the microscopes including a fixed target comprising a clear window, with a black dot in the center surrounded by clear concentric rings, affixed to a fixed arm of the gripper.

17. The apparatus as in claim 1, further including a means of introducing a single slide for priority analysis.

18. The apparatus as in claim 1, further including at least one camera in communication with the computer to capture digital images from the two microscopes.