U.S. patent application number 09/826138 was filed with the patent office on 2002-10-17 for high-precision computer-aided microscope system.
This patent application is currently assigned to AccuMed International, Inc.. Invention is credited to Mayer, William J..
Application Number | 20020149845 09/826138 |
Document ID | / |
Family ID | 23743497 |
Filed Date | 2002-10-17 |
United States Patent
Application |
20020149845 |
Kind Code |
A1 |
Mayer, William J. |
October 17, 2002 |
High-precision computer-aided microscope system
Abstract
A microscope frame structure having a front brace for added
stability and having a dual plate structure. The front brace is
rigidly coupled to the front ends of an upper portion and a base
portion. The upper portion then carries optical elements such as a
camera for instance. In effect, the optical elements thus reside on
a bridge structure, with substantially the same structural support
at both ends of the bridge. The arrangement is particularly useful
in automated specimen imaging and analysis systems. The dual frame
is composed of an upper plate, which supports a sample, a lower
plate which contacts an elevating screw, and a spacer post in
between the upper plate and lower plate. This configuration allows
for more stable movement of samples.
Inventors: |
Mayer, William J.; (South
Barrington, IL) |
Correspondence
Address: |
Kevin C. Harrison
Merchant & Gould P. C.
P. O. Box 2903
Minneapolis
MN
55402-0903
US
|
Assignee: |
AccuMed International, Inc.
|
Family ID: |
23743497 |
Appl. No.: |
09/826138 |
Filed: |
April 4, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09826138 |
Apr 4, 2001 |
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09439150 |
Nov 12, 1999 |
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6285498 |
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09826138 |
Apr 4, 2001 |
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09174140 |
Oct 16, 1998 |
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6151161 |
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09826138 |
Apr 4, 2001 |
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PCT/US98/21953 |
Oct 16, 1998 |
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60064558 |
Oct 17, 1997 |
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60064559 |
Oct 20, 1997 |
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Current U.S.
Class: |
359/391 ;
359/368; 359/390 |
Current CPC
Class: |
G02B 21/086 20130101;
G02B 21/24 20130101; G02B 21/362 20130101 |
Class at
Publication: |
359/391 ;
359/368; 359/390 |
International
Class: |
G02B 021/00 |
Claims
I claim:
1. A microscope system comprising, in combination: a base portion
extending from a front end to a back end; an upper portion
extending from a front end to a back end; a back support extending
from the back end of the base portion to the back end.backslash. of
the upper portion and providing rigid support of the back end of
the upper portion in relation to the back end of the base portion;
a stage for supporting a specimen, the stage being movable in
relation to the base portion, the upper portion and the back
support; a brace rigidly connecting the front end of the base
portion to the front end of the upper portion; and an optical
element mounted on the upper portion between the back support and
the brace.
Description
REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Patent
Application Serial No. 60/064,558, filed Oct. 17, 1997 and to U.S.
Provisional Patent Application Serial No. 60/064,559, filed Oct.
20, 1997. Moreover, this application is a continuation-in-part of
U.S. Patent Application Ser. No. 09/174,140, filed Oct. 16, 1998
and PCT Application Serial No. PCT/US98/21953 filed Oct. 16,
1998.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention is related generally to the field of
microscopy, and more particularly to the configuration of optical
microscopes and microscope-based electronic imaging systems.
[0004] 2. Description of the Related Art
[0005] In its most basic form, a microscope typically includes a
base, a plate or stage for holding a sample, a magnifier commonly
including a series of lenses, and a viewer for presenting a
magnified image to an observer. The principal purpose of a
microscope is to create a magnified image of a sample of a specimen
and to accurately present the enlarged image to an observer or to
an electronic imaging apparatus used for image acquisition,
display, measurement, analysis, communication, archiving, or data
management.
[0006] Over the years, microscopes have evolved into very complex
and sophisticated optical instruments, taking a variety of forms.
While most microscopes are manually operable and may present a
magnified image for viewing by an operator, one of the most
important recent advances in microscopy has been the development of
automated, computer-aided microscopes. Most computer-aided
microscopes include the conventional elements of manually operated
microscopes but are further configured in combination with a
digital computer. The computer may serve a variety of functions,
such as, for instance, controlling the position of a motorized
stage, controlling the focusing system, or controlling other
optical components such as microscope objectives.
[0007] In a typical arrangement, a computer-aided microscope system
includes an electronic photodetector or imaging system such as a
video or CCD camera interconnected to the viewer, with the output
from the detector being fed into a computer processor for a variety
of functions including analysis or image enhancement or display.
The computer processor in turn may provide control signals to the
microscope, for instance, to control the stage position, focus
drive or other aspects of the system. Provided with this
arrangement, a computer-aided microscope may enable the automatic
analysis of a wide variety of objects, such as cytological samples,
pathology specimens or semiconductor chips (solid state devices).
Further, the automated analysis may be easily enhanced by
appropriate computer programming as well as by the addition of
assorted peripherals (such as data storage devices and interactive
user-input devices).
[0008] In automated cytology sample analyses, for instance, a
specimen is drawn from a patient, a sample is prepared from that
specimen, and the sample is placed into the automated microscope.
An image detector (e.g., CCD camera) may electronically scan the
sample and thereby receive digital images of discrete regions of
the sample. The detector may then feed these digital images to a
processor, which stores the images in memory and analyzes the
images. In addition, the processor may receive from the microscope
an indication of the spatial coordinates of the stage (e.g., X and
Y planar coordinates, and a Z focus coordinate). Through complex
image analysis algorithms, the processor may identify cellular
matter of interest in the sample and may then mark in memory an
indication of the stage position coordinates associated with that
cellular matter. Samples may be deposited on slides with fiducial
marks to ensure that the X-Y locations are accurate from microscope
to microscope or calibration procedures can be developed and used
to ensure that the X-Y coordinates apply from machine to
machine.
[0009] In turn, once the processor completes its analysis, it may
generate a routing function keyed to the stage coordinates and
defining an order by which the automated microscope should present
areas of the sample to an operator such as a cytotechnologist.
Through use of this routing function, the computer processor may
thus control the microscope stage position and microscope focus,
and may thereby present the cellular matter or other objects or
optical fields of interest to the operator through the microscope
field of view. In addition, or alternatively, the
automated-microscope system may be configured to include a computer
monitor, which may present the microscopic fields of view to the
operator without requiring the operator to look through the
microscope ocular(s).
[0010] As a general rule, precision, accuracy and speed are
critical to the useful operation of a microscope in addition to the
quality (e.g., resolution) of the optical magnification devices and
processes. This is particularly important for computer-aided
microscopy systems. In cytological specimen analysis, for instance,
a cytotechnologist typically needs to be able to locate atypical or
abnormal cells in specimens rapidly, precisely and accurately,
since cells are typically less than a few hundred microns in their
maximum linear dimension. While many cancer-related cytological
changes are characteristic and can be detected and classified with
a high degree of accuracy by an appropriately configured
microscope, inaccurate or imprecise microscope configurations can
be the source of unacceptable false positive or false negative cell
classifications and sample specimen diagnoses.
[0011] Further, modern vision systems employing computer-aided
image analysis have imposed on microscopes even more stringent
requirements for high precision, mechanical stability and optical
and illumination repeatability. Unfortunately, however, traditional
mechanical (e.g. fully manual) microscope systems, as well as many
of the currently available automated microscope systems, have not
provided the positional accuracy, repeatability, stability and
resolution required for reliable, reproducible quantitative
microscopic imaging applications.
[0012] To ensure proper operation, for instance, a microscope must
be as stable as possible. The microscope must be stable in the
presence of ambient vibrations and also stable with respect to
internally introduced vibrations. However, the motorized stages in
some existing automated-microscope configurations are unstable.
Consequently, these existing systems cannot rapidly, accurately,
precisely and repeatedly locate and focus on diagnostically
significant areas of a sample from a specimen.
[0013] Traditional optical microscopes, for example, enable
movement of the stage by way of a cantilevered system that is
offset from the optical path of the microscope. In other systems,
as the present inventors have recognized, the stage is moved
through the exertion of a force at a position other than the center
of gravity or center of effort of the plate. Consequently, existing
microscopes tend to generate yaw, pitch, roll and droop errors
(i.e., introduce a third derivative, "jerk") during stage movement.
These errors are particularly troublesome in the context of
automated computer-aided microscopy. It is also problematic for
human observers who also need stage motion to be dampened before
they can visualize a temporally stable image.
[0014] Similarly, in microscope systems that employs a detector
(such as a camera) to capture magnified images, the detector itself
must remain stable during operation. However, in most such systems,
the detector is attached only to the viewer of the microscope. As
recognized by the present inventors, this configuration thereby
increases the likelihood that the camera will become unstable or
misaligned during operation, potentially rendering the camera
unable to capture magnified images properly.
[0015] Further, to ensure proper operation, the sample being
analyzed in a microscope needs to be properly illuminated and have
proper spectral density. This is particularly the case in
microscopes that employ detectors, such as cameras, to capture
magnified images, as the detectors are often configured to operate
optimally with a particular level of light. This is also the case
whenever there is spectral-based analysis of a sample. In these
systems, if the sample is illuminated with insufficient or
excessive light, or with improper spectral characteristics, the
detector may need to compensate for the imperfect illumination and
thereby operate less than optimally. Still further, the level of
illumination in a microscope is important even for manual viewing
through the oculars, as appropriate illumination is required to
allow human perception of the magnified sample through the
microscope lenses.
[0016] Additionally, a typical microscope includes a variety of
adjustable elements. These elements include, for instance,
condenser lens focus, condenser lens centration, lamp filament
centration, condenser aperture, and field diaphragm. To ensure
proper operation of the microscope system, most or all of these
elements need to be adjusted by an operator or an automated
controller before analysis can begin. For example, to properly
focus a diffused image at the light source, the condenser lens
focus must be properly adjusted. As another example, to achieve
lamp photon emitter centration, an operator must typically adjust
the microscope light source if the light source is not properly
centered. Unfortunately, however, adjustment of these elements can
be time consuming and tedious.
[0017] In view of the deficiencies in the art, there is a need for
an improved configuration of a high-precision, automated or
computer-aided microscope.
SUMMARY OF THE INVENTION
[0018] An exemplary embodiment of the present invention provides an
improved microscope system. In one aspect, the system includes an
improved method and apparatus for guiding the plate. In a second
aspect, the system includes an improved method and apparatus for
moving the stage. In a third aspect, the system includes an
improved method and apparatus for maintaining proper illumination.
In a fourth aspect, the system includes an improved method and
apparatus for maintaining proper spectral density. In a fifth
aspect, the system includes an improved method and apparatus for
maintaining proper placement of the light source, for configuring a
fixed optics system. In a sixth aspect, the system includes an
improved method and apparatus for maintaining proper placement of
the imaging system. In a seventh aspect, the system includes an
improved method and apparatus for fixing the optics in the
microscope for an automated system. In an eighth aspect, the system
includes an improved method and apparatus for increasing the
stability of the microscope during movement.
[0019] The invention may facilitate enhanced electronic image
capture and analysis and may be particularly suitable for use in
the context of cytological or histological sample analysis.
However, the invention is not limited to analysis of biomedical
specimens but may more generally be used for analysis of any type
of sample.
[0020] A principal object of the present invention is to provide a
computer-aided microscope system that facilitates quick, stable and
reproducible microscopic presentation of goals. Another objective
of the invention is to provide a microscope having geometric
accuracy in the three-motion axes. Still another object of the
invention is to provide a microscope that remains stable when
performing high-speed moves.
[0021] A further object of the invention is to provide a microscope
that does not vary appreciably in terms of optical alignment. Yet a
further objective of the invention is to provide a microscope that
has constantly controlled and repeatable illumination systems.
Still another object of the invention is to provide a microscope
that may be incorporated into higher level imaging and analytical
instruments. Yet another object of the invention is to provide a
microscope in combination with a detector, such as a camera or a
photomultiplier tube assembly, whereby the photodetector(s)
remain(s) in proper alignment during their image acquisition
operation.
[0022] These and other features and advantages of the present
invention will be better understood by reading the following
detailed description, with appropriate reference to the
accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0023] Exemplary embodiments of the present invention are described
herein with reference to the drawings, in which:
[0024] FIG. 1A is a perspective view of a microscope system in an
embodiment of the invention, in combination with other components
such as a display, barcode reader, and slide magazine;
[0025] FIG. 1B is a perspective view of two microscopes in another
embodiment of the invention;
[0026] FIG. 2A is a side cutaway view of a guidance system for a
microscope assembly according to an embodiment of the
invention;
[0027] FIG. 2B is a front cutaway view of the guidance system, a
stage and light assembly of the microscope assembly shown in FIG.
2A;
[0028] FIG. 2C a side cutaway view of position switches in the
microscopic assembly;
[0029] FIG. 2D is a front cutaway view of a lower portion of the
microscope assembly shown in FIG. 2B;
[0030] FIG. 2E is a side cutaway view of the stage, including a
z-axis plate, of the microscopic assembly shown in FIG. 2A;
[0031] FIG. 2F is a top cutaway view of the stage of the
microscopic assembly shown in FIG. 2A;
[0032] FIG. 2G is a top cutaway view of the microscope assembly
shown in FIG. 2A;
[0033] FIG. 2H is a front cutaway view of the microscope assembly
shown in FIG. 2A;
[0034] FIG. 2I is a side cutaway view of the microscope assembly
shown in FIG. 2A;
[0035] FIGS. 3A-3D are cutaway views of the focus drive and
switches of the microscope assembly shown in FIG. 2A;
[0036] FIG. 4A is a side cutaway view of the centralized filament,
mirrors and lenses of the microscope assembly shown in FIG. 2A;
[0037] FIG. 4B is a cutaway view of the light source assembly shown
in FIG. 4A;
[0038] FIG. 4C is a block diagram of the light feedback system for
the light source assembly shown in FIG. 4A;
[0039] FIG. 4D is a flow chart depicting operation of the light
feedback system shown in FIG. 4C;
[0040] FIG. 4E is a diagram of a color temperature measurement
system employed in an embodiment of the invention;
[0041] FIG. 4F is a graph of current versus wavelength to determine
the color temperature;
[0042] FIG. 4G is a flow chart illustrating steps for determining
and modifying the light level in a microscope system according to
an embodiment of the invention, in order to facilitate operation at
a predetermined spectral distribution;
[0043] FIG. 5A is a fixed condenser geometry of an imaging system
configuration of the microscope assembly shown in one embodiment of
the invention;
[0044] FIG. 5B is a top cutaway view of the fixed condenser
geometry of FIG. 5A;
[0045] FIG. 5C is a side cutaway view of the fixed condenser
geometry FIG. 5B;
[0046] FIG. 6 is a side cutaway view of a microscope assembly and
imaging system according to another embodiment of the
invention;
[0047] FIG. 7 is a perspective view of the base and bridge of the
microscope assembly;
[0048] FIG. 8 is a side cross-sectional view of the microscope
assembly including the bridge, base and optical center line;
[0049] FIG. 9A is a perspective view of the Z-axis plate,
guideposts, spacer post, bushings, lower plate and collar of the
microscope assembly;
[0050] FIG. 9B is a cross-sectional view of the Z-axis plate,
guideposts, spacer post, bushings, lower plate, collar, base and
elevation screw of the microscope assembly;
[0051] FIG. 9C is a top view of the collar;
[0052] FIG. 10 is a cross-sectional view of the Z-axis elevation
screw drive including the nut, elevating screw, collar, radial
bearings, thrust bearing and base;
[0053] FIG. 11A is a perspective view of a microscope system in an
embodiment of the invention which includes a rotating wheel;
and
[0054] FIG. 11B is a top view of the rotating wheel with slots.
DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT
[0055] Referring to FIGS. 1-6, there is shown a schematic block
diagram of a system that incorporates the principles of the
invention. In particular, the Figures illustrate a system having
the capability to capture images of a sample from a specimen
collected from an individual and placed upon a slide, and to
analyze the sample rapidly, accurately, and precisely. The
microscope system may be incorporated into a variety of settings
and a variety of applications.
[0056] Exemplary Applications for Microscope System
[0057] Referring to FIG. 1A, there is shown one example of a
suitable configuration employing a microscope system according to
the present invention. An automated video microscope having image
analysis capabilities is coupled to a Data Management System (DMS).
In one embodiment of the invention, the DMS comprises a
conventional computer system with a processor and memory that
contains patient medical history and demographic data relevant to
the specimens being screened. The DMS preferably takes the form of
a programmed general purpose desktop IBM-PC compatible computer
which has sufficient storage and processing capability to run the
Microsoft Windows operating environment and the Microsoft Visual
Basic and Microsoft Access application programs. The DMS and the
image analyzer are preferably coupled via a high-speed serial data
link. The DMS may also be coupled to other data processing
equipment via various types of local or wide area networks. In
alternative embodiments, other data computing equipment may be used
as would be known to persons of ordinary skill in the art. As shown
in FIG. 1A, a slide magazine 18, a bar code scanner 21 and display
17 may be used in combination with the microscope.
[0058] Referring to FIG. 1B, there is shown a second application of
the microscope. Automated sample analysis system 23 includes a
microscope with fixed optics, described subsequently, and a
computer system. Samples are input via a slide magazine feeder 19
and analyzed with the computer in combination with the microscope.
The data from the analysis is sent via a cable 24 to an
operator-based sample analysis system 25, which also includes a
microscope. The operator-based sample analysis system 25 receives
the data from the automated sample analysis system 23, and, with
the assistance of the data, facilitates presentation of areas of
the sample to the operator for analysis.
[0059] The microscope may be used in combination with a detector
for sensing the magnified image of the sample, as discussed
subsequently with respect to FIG. 6. In one embodiment, the
detector is a high resolution, scientific grade charge coupled
device ("CCD"), such as may be used in a video camera. However, the
invention is not limited to use of a CCD, but may use other means
for capturing or viewing an image. Such devices may include, for
instance, in addition to CCD cameras and traditional video cameras,
photomultiplier tube (PMT) assemblies. The camera is preferably
affixed to a video-port on top of the eyepiece of the microscope in
order to capture cell images. A variety of cameras are available,
depending on the resolution requirements (including spectral
resolution, spatial resolution, photometric resolution and temporal
resolution) of the user. Three available video cameras include the
Pulnix TM-1001 available from Pulnix Corp. of Sunnyvale, Calif.,
the Kodak Megaplus ES1.0 from Eastman Kodak of Rochester, N.Y. and
the SMD 1M15 from Silicon Mountain Devices of Colorado Springs,
Colo. A lens with 10.times. magnification, 4.0 numerical aperture
(other magnifications or numerical apertures may be chosen
depending on the ultimate application), provides the combination of
a large field of view as well as the high spatial resolution to
facilitate efficient specimen screening by a single objective
lens.
[0060] Images received by the camera are captured by a Data Raptor
type frame grabber available from Bit Flow Corp., Woburn, Mass.,
and transferred to an image analyzer for analysis. The microscope
and image analyzer are coupled by a serial data link which permits
the image analyzer to initiate control of an autofocus function on
the microscope and to capture specimen position information. The
microscope is preferably controlled by a controller board, which is
described in further detail in U.S. Pat. No. 5,930,732, entitled
"System for Simplifying the Implementation of Specified Functions,"
the entirety of which is hereby incorporated by reference.
[0061] General Arrangement
[0062] Referring to FIGS. 1 and 2A-2G, there are shown various
views of a microscope 10. In the exemplary embodiment, microscope
10 includes a number of sub-elements, including a base 12, a Z-axis
plate 13, a Y-axis slide 14, an X-axis slide 15, magnifying
lens(es) (such as objective 16), slide holder 19, eyepiece 20, and
light source 77. The Z-axis plate 13 supports the slide containing
the sample and can move the sample in the Z-direction, as shown in
the Figures. As further shown in FIG. 2F, the Y-axis slide 14 moves
the sample in the Y-direction via a motor 43, and the X-axis slide
15 moves the sample in the X-direction via a motor 41. The slide is
held in a carriage 45 which moves in the X-direction.
[0063] Base 12 provides rigid support for the microscope and, as
shown in the Figures, may form the bottom portion of the
microscope. In an alternative embodiment, the base may include an
upper portion as shown in FIG. 6, as discussed subsequently.
Moreover, in FIGS. 2A-2D and FIGS. 2G-2I, the light source 77 is
attached to the base and the path of light from the light source 77
travels through the base. In an alternate embodiment, the light
source 77 may be attached to an upper portion of the
microscope.
[0064] The controller board within the microscope 10 receives
signals from the multifunctional control unit. The controller board
preferably generates and transmits signals to control the operation
and movement of the aforesaid components of the microscope, and to
transmit and receive information generated by sensors on the
microscope, via ports 66 as shown in FIG. 2A, to and from the DMS.
In some embodiments, the controller board may control the
transmission and selection of information between the microscope
10, camera, frame grabber, image analyzer, and the DMS. In still
other embodiments, the controller board may be used to control the
operation and movement of the components of the microscope 10. The
images received from the microscope 10 may also be selectively sent
to a computer for processing. The controller board also controls
the light level, the power turret, which selects the lens for
viewing the sample, the stage translation speed, the spatial
orientation of the sample on the Z-axis plate 13, the Y-axis slide
14 and the X-axis slide 15, and the intensity and color
temperature/illumination control.
[0065] Referring to FIG. 2C, there is shown a side cutaway view of
the lower portion of the microscope including position switches 58.
Included in this portion is the stage 27, which is shown as side
and top cutaway views in FIGS. 2E and 2F, respectively. The stage
27 typically is the portion of the microscope that provides
movement of the sample. The stage 27 may move upward and downward
during focusing and may include a plate, such as a Z-axis plate 13.
A plate may be an object that, either directly (by direct physical
contact) or indirectly (through another object), holds the sample.
In a preferred embodiment, the stage 27 includes the Z-axis plate
13, the Y-axis slide 14, the X-axis slide 15, the condenser lens
system 29, and guideposts 55. As discussed subsequently, the Z-axis
elevation system employs an elevating screw which is in contact
with the lower portion of the Z-axis plate 13. Moreover, movement
in the x-direction and y-direction is performed by motor 41 and
motor 43, respectively.
[0066] Vertical Movement and Guidance of Microscope Stage
[0067] Because of the design of the present invention, the
microscope 10 is very precise and accurate. The improved microscope
10, for instance, enables a cytotechnologist or other observer to
rapidly, precisely and accurately locate objects of interest with
the requisite positional accuracy and precision, e.g., in
cytological applications, within .+-.5 microns. In addition, the
microscope of the present invention may be manufactured at a
moderate price while still maintaining high precision. In
particular, the invention permits development of a system of
precise tolerance components which, when assembled with a thermoset
plastic material, yields the required performance accuracy. In
addition, the system has proven to be dimensionally stable. In
order to achieve a level of accuracy and stability similar to the
present invention, a conventional microscope would require
extremely precise components, rendering the cost of the microscope
financially impractical.
[0068] The stage 27 is moved along the Z axis by a device that
applies force at a specific point on an underside of the Z-axis
plate 13. As discussed subsequently, the Z-axis elevation system
employs an elevating screw 89 which is in contact with the lower
portion of the Z-axis plate 13. The force is preferably applied at
a single point via the elevating screw 89, which, in a preferred
embodiment, works in combination with a motor assembly. The
elevating screw 89 is, in one embodiment, 8 mm in diameter with a
0.5 mm pitch. This placement of a single, specific point of force
on the Z-axis plate 13 of the stage provides for greater stability
when moving the stage 27. If a single point of force for moving the
stage 27 is chosen, it is preferably applied at, or substantially
at, the center of gravity of the stage 27 in order to reduce the
amount of geometric errors. This configuration improves over
typical microscopes, in which the manner of moving the stage is to
apply force to the plate at points that are not at the center of
effort or gravity. For example, a typical cantilever bearing system
(commonly referred to as the knee and column design) may increase
the possibility of geometric errors while viewing due to the offset
manner of moving the stage. Moreover, as the inventors have
discovered, this prior art method creates instability while moving
the stage.
[0069] According to the current method and apparatus, the force for
moving the stage upward and downward is concentrated at the center
of gravity 139 of the stage (which includes the X-axis slide 15,
Y-axis slide 14 and Z-axis plate 13), as shown in FIG. 2G. In this
manner, the point of force for moving the stage is preferably
limited to a single point, typically the center of effort. In an
alternative embodiment, there may be a multitude of forces applied
at various points on the plate to move the Z-axis plate 13 (and in
turn the stage 27) upward and downward. The net effect of these
forces is that there is an upward or downward force at, or
substantially at, the center of gravity of the stage. For example,
a multitude of forces may be applied at different points on the
stage, with the net force being at the center of gravity of the
stage and in the Z direction or in the direction of the optical
path. In addition, the application of force at this point
inherently maintains stability of the system during movement. The
device, or "forcer," that is used to apply force to one point may
take a variety of forms. As examples, the forcer make take the form
of a piston, lead screw, finger, lever, column, cam, gear system
using rack and pinion, or piezoelectric device or voice coil.
Referring to FIGS. 2H and 2I, there are shown front and side
cutaway views of the microscope assembly.
[0070] In the exemplary embodiment, the arrangement for vertically
moving stage 27 advantageously takes the form of a single jack
screw sitting in a radial/axial thrust bearing system. Referring to
FIGS. 3A and 3B, this arrangement is shown in more detail as
apparatus 56 located beneath the Z-axis plate 13. The assembly of
this apparatus contains radial ball bearings 57 and nut 87 fixed
within the bearings 57. Specifically, ball bearings 57 have an
inner race in contact with nut 87 and an outer race in contact with
base 12 (so that the outer race does not move). An elevating screw
89, which is in contact with the Z-axis plate, engages nut 87.
[0071] The Z-axis plate 13 is gravity-loaded against a thrust
bearing for the elimination of focusing hysteresis (backlash) while
moving the Z-axis plate 13. In an alternative embodiment, the
elevating screw, or other means for applying force at one point to
the Z-axis plate 13, may be attached to the Z-axis plate 13. A
synchronous timing belt and pulley system 61 coupled to a motor 59.
As shown in FIG. 3A, the motor 59 is adjacent to the ball bearings
57 and nut 87. Thus, when the Z-axis plate is to be moved
vertically, the motor assembly 59 moves the pulley 61, which then
turns the nut 87 and the inner race of bearings 57. The nut 87 in
turn moves the elevating screw 89. Via a coupling 103, the
elevating screw 89 moves the Z-axis plate 13. In the exemplary
embodiment, the elevating screw is an 8 mm diameter hardened ball
screw with a pitch/lead of 0.5 mm, and the net result of the gear
reduction is that one microstep (or one step of the motor) equals
{fraction (1/16)} micron elevation of the stage.
[0072] The screw may be made of a heat treatable steel such as
Timken ball bearing steel (AISI-52 100). Preferably, the elevation
screw, the nut and the balls are all made of the same material,
treated to a high level of hardness, such as Rc-62/64. In that way,
it is believed there will be no possibility of brinelling (i.e.,
the disruption of smooth surfaces from interplay between
components), which could otherwise interrupt the smooth rolling of
balls 57 and give rise to abrupt motion.
[0073] As thus shown and described, in the exemplary embodiment,
the arrangement of components that move the stage vertically, i.e.,
the elevating screw 89, the nut 87, and the bearings 57 (as well as
a portion of pulley assembly 61), forms a single-column assembly.
As further shown in FIG. 3A, this single-column assembly is rigidly
mounted to base 12 by bosses 35, which is a raised surface that is
part of the base 12, machined to accept the single column
assembly.
[0074] Further, this single-column arrangement is itself inherently
very rigid compared to the typical microscope focus systems, which
usually employ gear box designs. In traditional arrangements, a
focus system may go through a 12-14 gear reducer system, which
normally has large hysteresis, play, lash and spring. With such
systems, manufacturers typically cannot guarantee less than 5
micron hysteresis. With the present jack screw arrangement, in
contrast, dramatically fewer parts are required. In effect, the
screw 89 itself can be static (except for up and down movement),
and the only moving part might be nut 87, which rotates in the
radial axial bearing arrangement. Advantageously, this arrangement
should be able to provide closer to {fraction (1/16)} micron or
better hysteresis, a significant improvement over the existing
art.
[0075] Turning back to FIG. 2G, there is shown the motor assembly
137 that applies a point of force on the Z-axis plate 13 at the
center of gravity 139 of the Z-axis plate 13. In an alternate
embodiment, as shown in FIG. 3B, the motor assembly may be offset
from the center of gravity of the Z-axis plate 13.
[0076] The stage 27 theoretically does not require anything for
operation in addition to the elevating screw 89 and the associated
motor assembly. This is due to the fact that the elevating screw 89
moves the stage 27 at its center of gravity. However, on a
practical level, the stage 27 may experience movement in the X and
Y directions during operation. For example, the elevating screw 89
is designed to provide thrust in the Z-direction. In addition to
the thrust, there may also include lateral movement in the X-
and/or Y-direction. In order to reduce or minimize this movement, a
guidance system is used. The guidance system assists in maintaining
proper alignment of the stage 27 with respect to the optical axis.
The guidance system of the microscope of the present invention is
preferably centered or substantially centered around the optical
path through the Z-axis plate 13 of the microscope. An optical path
is defined as the path through which light passes through the
microscope. One portion of the optical path is through the stage 27
of the microscope. Of primary importance are the stability and
geometric accuracy of the system at the optical path. According to
a preferred embodiment, this stability may be achieved by centering
the guideposts around the optical path. This is in contrast to
guidance systems of typical microscopes, which are not centered
around the optical path of the microscope and which may have an
overhang of components. These existing systems are typically
unstable and are thereby prone to producing yaw, pitch and droop
errors of the stage (and therefore the image) due to a lack of
stability in design.
[0077] In an exemplary embodiment, the method for guiding the
Z-axis plate 13 is via a plurality of guideposts 55, as shown in
FIGS. 3A-C. Each of the guideposts 55 is preferably equidistant
from and approximately symmetrically placed around the optical path
through the Z-axis plate 13. As shown in FIG. 2G, the center of the
locus of points of the guidance system for the Z-axis plate 13 and
stage 27 is coincident with the optical path. For example, the
guidance system may be clustered in an array, with the array being
any number greater than one. The center of that array should be
coincident with the optical path. So that, if one takes a
cross-section of the guidance system perpendicular to the optical
path, that center of the array is at or substantially at the
optical path.
[0078] The guidance system in one embodiment includes two portions,
one portion being a part of or attached (either removably or
permanently) to the stage or the plate (such as the Z-axis plate)
and the other portion being a part of or attached (either removably
or permanently) to the base. For example, in one embodiment, the
guideposts 55, which are attached to the Z-axis plate 13, are the
first portion and ball bushings 54, which are attached to the base
12, are the second portion. The guideposts 55 and the ball bushings
54 mate with each other to stabilize movement, and are discussed
subsequently with respect to FIGS. 3A-D. The guidance system in
another embodiment includes two portions, one portion being an
integral part of the stage or plate and the other portion being an
integral part of the base. For example, the Z-axis plate may have
holes which engage guideposts that are integral with the base or
are affixed to the base. In an alternative embodiment, a plurality
of guideposts at varying distances from the optical path are used.
In particular, a first set of guideposts is a first predetermined
distance from the optical path (with each guidepost being at the
same first predetermined distance from the optical path) and first
angular disposition (the guideposts being distributed around the
circumference of the optical path), whereas another set of
guideposts is at a second predetermined distance from the optical
path (with each guidepost being at the same second predetermined
distance from the optical path) and second angular disposition (the
guideposts being distributed around the circumference of the
optical path).
[0079] Referring to FIGS. 2E and 3A-D, there are shown cutaway
views of the focus drive and switches of the microscope assembly.
Three bore holes 51, 52 and 53, discussed subsequently, are placed
in the Z-axis plate as shown in FIG. 2G. Moreover, recirculating
ball bushings 54, as shown in FIG. 3A, are attached to the base 12
and are preloaded into the bore holes 51, 52, 53 of the Z-axis
plate. The recirculating ball bushings 54 act as guidepost mates
that engage the guideposts 55. Guideposts 55, preferably machined
to a tolerance of millionths of an inch, are affixed to the bore
holes 51, 52, 53 and run in the bushings 54. The bushings 54 and
the guideposts 55 are designed such that they operate with
essentially zero clearance. In particular, the bushings 54 contain
bearings that are rolling balls operating in an interference mode
with the guideposts 55, so that there is no off-axis motion. Thus,
the movement of the stage 27 is vertical with no lateral play. Due
to this design, the stage 27 may operate with vertical movement
typically in {fraction (1/16)} micron increments. Other types of
guidance systems, such as a linear bearing system, flexure plates,
air or magnetic bearings or a dovetail slide with gibs system, are
possible as well. Moreover, as shown in FIG. 3C, one of the
guideposts 55 is extended in length so that at a certain level, the
guidepost engages switches 58. The switches 58 thereby may indicate
the position of the Z-axis plate 13.
[0080] Referring to FIGS. 2A-C, there is shown side, back and top
cutaway views of the microscope assembly, respectively. The optical
microscope 10 includes a stress annealed aluminum Z-axis plate,
having precision bored holes 51, 52, 53. These holes are preferably
bored with a key tolerance of about 10 microns. The number of bored
holes may vary depending on the mechanics of the microscope
assembly. The heat treating of the cast aluminum member increases
dimensional stability. In addition, the precision bored holes allow
the Z-axis plate 13 to move along the optical path in a smooth
manner, i.e., without jittery, shaking or jerky motions, during
scanning and focussing. The Z-axis plate 13 is preferably cast
aluminum, which may be rough machined. Then, the Z-axis plate 13
may undergo heat treatment for stress relief. Thereafter, the holes
may be precisely bored into the Z-axis plate 13 so as to be aligned
accurately and non-changeably with time. Therefore, due to the
centration of the guidance system around the center of gravity,
errors of droop, pitch and yaw tend to nullify or to cancel
themselves to zero.
[0081] Light Source Alignment and Emission
[0082] Referring to FIG. 4A, there is shown a side cutaway view of
the centralized filament, mirrors and lenses of the microscope
assembly. Condenser lenses 63, 65 receive light through a numeric
aperture diaphragm 67, which in turn receives light through a
mirror system 69, through a field diaphragm 71, a filter diffuser
73, a second mirror system 75, a second filter diffuser 76. Light
is generated by a halogen light source or any other light source
with a centralized photon emitter (i.e., illumination source).
Means have been developed for a photon emission module to be easily
replaced without the necessity of complicated or costly efforts at
realignment of parts or processes, as discussed subsequently.
[0083] In addition, light may be generated from any light source
whose photon emitter (e.g., filament) is at a predetermined
location from the base, screw or other mounting geometry of the
light source. Once the base or other mounting geometry is properly
aligned, the photon emitter is likewise aligned with the optical
path due to the predetermined nature of the light source. The
optical alignment is therefore obtained by machining components
rather than by adjusting the light source, thereby minimizing
error. In the case of a centralized photon emitter, the photon
emitter is centered with the base or other mounting geometry of the
light source.
[0084] Such an automated system requires precisely defined
illumination. Such defined illumination is required when the system
is initially used, throughout the life of use of the lamp (which
may decrease in its illumination over time), and throughout the
life of any replacement lamps. The present invention thus maintains
consistent and precise illumination throughout use of the
microscope. In conventional systems, when a light source is
initially installed or replaced, the system must be realigned by a
technician in order to minimize uneven illumination which may be
received by the camera. In an embodiment of the current invention,
the design of the system and the light source are such that the
system is pre-centered due to the predetermined spatial
relationship of the photon emitter with the mounting geometry of
the light source and due to the mounting mechanism for the light
source on the microscope. Thus, when a light source burns out,
replacement of the light source automatically centers the photon
emitter, as described below (within 2 thousandths of an inch of the
theoretical center line).
[0085] Referring to FIG. 4B, there is shown a cutaway view of the
light source assembly. The light system is unlike a conventional
microscope light source configuration, at least in part, since it
has a photon emitter that is at a predetermined spatial location
relative to a reference feature of its housing (e.g., the base 92
or the mounting mechanism for the light source) and due to the
mounting mechanism of the microscope. In a preferred embodiment,
the light source 77 is a halogen light source with a photon emitter
94 that is at a predetermined spatial location with the base 92,
due to precise and accurate manufacturing of the light source. The
distance from the base to the photon emitter is 20 millimeters in
the Welsh Allen, part no. 1036-1. Since the light source 77 is
designed to have a photon emitter 94 at a predetermined axial and
radial distance from the base 92 of the light source, the base 92
may be correctly positioned thereby correctly positioning the
photon emitter. In this manner, the design of the illumination
system enables lamps to be installed with near perfect
centration.
[0086] In the present invention, any light source may be used,
depending on the power requirements, so long as the photon emitter,
or the means for generating the light, is at a predetermined axial
distance from the base of the light source (i.e., the predetermined
distance from one light source to the next is the same within an
acceptable tolerance). In a preferred embodiment, a halogen light
source is used. In addition, a light source in combination with a
fiber optic cable, an incandescent light source, a light emitting
diode (LED), an arc lamp (e.g., xenon arc lamp or mercury arc
lamp), or other such light source (with or without wavelength
selection means) may be used.
[0087] The optical path 96 of the system is designed to be directed
from the center of the halogen light source with a centralized
photon emitter or filament. Therefore, the halogen light source
with a centralized photon emitter sends light directly (and with
minimal shadowing) onto the physical image on the slide. In
particular, in a preferred embodiment, the lamps are manufactured
by Welsh Allen, part no. 1036-1, 30 watt halogen light sources with
a centralized photon emitter. The housing 79 that receives the lamp
is also designed such that the halogen light source with a
centralized photon emitter 77 may be placed with maximum accuracy
and placement reproducibility. In this manner, when the base of the
light source is positioned properly, the photon emitter of the
light source is positioned properly as well.
[0088] The housing 79 contains a mounting mechanism for receiving
the light source. The mounting mechanism is designed to receive the
light source 77 precisely, both concentrically and axially. The
mounting mechanism, in one embodiment is an accurate and precise
boring of a hole 91 in the housing 79. Other mounting mechanisms,
such as clamps, may be employed wherein the mounting mechanisms
concentrically and axially place the light source in housing
79.
[0089] In addition, the hole 91 is of sufficient axial and radial
positional accuracy to provide the imaging system with a positional
tolerance of about 0.127 millimeters. This precision boring
receives the base 92 of the light source. In addition, a seat 95 is
precisely bored and/or shaved so that the base 92 of the light
source abuts the hole 91 in perfect alignment. The precision boring
of the hole 91 and the seat 95 thereby ensures that the base of the
light source 77 is in its proper placement. In addition, a threaded
hole 98 is bored to engage the screw mount 100. The screw mount 100
attaches the light source 77 within the housing 79 and makes
electrical contact with the compliant contact 102 in the housing
79. Because the photon emitter is at a predetermined location
relative to the base, the photon emitter of the light source 77 is
in proper alignment and centered at the optical center line. Power
is connected to the light source 77 via wires 97 and a connector
99.
[0090] In addition to proper placement of the light source, the
intensity of the light source can be controlled. In both an
operator driven system (in which, for example, the operator views
the magnified image through an eyepiece in the viewer) and a
detector based system (in which, for example, a detector, such as a
camera, receives the magnified image from the viewer and acts as an
electronic image viewer), the proper amount of light can be
generated to illuminate the sample. In particular, in a detector
based system, the detector may have an optimal light level (or
optimal light range) under which it operates. For example, when
using a camera, the camera has a range of optimal values of light
for operation. When the camera receives an image with less than the
optimal value of light, it adjusts the shutter speed to lengthen
the exposure time. Similarly, when the camera receives an image
with more than the optimal value of light, it adjusts the shutter
speed to shorten the exposure time. To better capture the image
from the detector, the light level should therefore be chosen so
that the detector operates in its optimal light range.
[0091] In order to accomplish this, a detector is used to sense
light that is in the optical path 96. The light travels from light
source 77 and is ultimately sent to the viewer. As shown in FIG.
4A, the light travels from the light source 77 to the second filter
diffuser 76 to the second mirror system 75 to the filter diffuser
73 to the field diaphragm 71 to the mirror system 69 to the numeric
aperture diaphragm 67 to the condenser lenses 63, 65. In order to
determine the intensity level of the light, the light may be sensed
at any point in the path of the light source through the
microscope. In FIG. 4a, the mirror system 69 is a 98/2 mirror that
reflects 98% of the incoming light and passes 2% of the light.
Behind the mirror system 69, a detector in the form of light
intensity monitor system 101 senses light that passes through the
mirror system 69. The light intensity monitor system 101 is an
electronic component such as a diode that feeds back information to
the computer system or processor, which controls the light level of
the lamp, as described subsequently. In addition, any form of light
detector may be used to sense the light.
[0092] There are methods in which to both sense and control the
intensity of the light. Referring to FIG. 4C, there is shown a
block diagram of one preferred embodiment of the light feedback
system. The light source 77 generates the light and has a power
sub-block 111. In one possible embodiment, the power sub-block 111
includes wires 97 and connector 99, which connects to one end of
the light source 77. The light is sensed by a detector 105. The
detector 101 sends its output to a processor 105, which contains a
comparator 107 and a look-up table 109. The look-up table 109 may
take the form of a permanent memory such as read only memory (ROM)
or a temporary memory such as random access memory (RAM). Depending
on the operation of the processor 105, described subsequently with
respect to FIG. 4C, the processor alters the amount of power to the
light source in order to adjust the level of illumination.
[0093] Referring to FIG. 4D, there is shown a flow chart for
determining and modifying the light level in the microscope system
to operate at a precise amount of illumination. A portion of the
light that is generated from the light source is sensed via a
detector, as shown at block 113. This value is sent to the
processor 105, which determines whether the amount of light
generated is within the optimal range. In particular, the processor
determines whether the light is greater than the upper bound of the
optimal range, as shown at block 115, or whether the light is less
than the lower bound of the optimal range, as shown at block 121.
In the preferred embodiment, as shown in FIG. 4A, because of the
98/2 mirror 70, the detector 101 senses 2% of the light. Therefore,
the processor 105 is able to determine, based on the sensed light,
how much light is being generated. In addition, the light may be
sensed at any point in the optical path, from near the photon
emitter 94 of the light source 77 to the condenser lenses 63,
65.
[0094] Look-up tables 109 in the processor 105 have a first
predetermined value and a second predetermined value. These values
define the amount of sensed light from the detector when the light
source is operating in the upper limit of the optimal range and the
lower limit of the optimal range, respectively. In addition, these
predetermined values may be generated during calibration of the
microscope. The first predetermined value indicates that the amount
of light in the microscope is at the upper limit of the optimal
range and the second predetermined value indicates that the amount
of light in the microscope is at the lower limit of the optimal
range. Using the comparator 107, the sensed light is compared with
the first predetermined value to determine if the sensed light is
greater than that value, as shown at block 115. If it is, then too
much light is being generated by the light source and the amount of
power to the light source should be reduced. The sensed light is
also compared to the second predetermined value to determine if the
sensed light is less than that value, as shown at block 121. If it
is less, then too little light is being generated by the light
source and the amount of power to the light source should be
increased.
[0095] To regulate the amount of power to the light source, the
processor first determines the amount of power that is currently
being given to the light source, as shown at block 117. In one
embodiment, this is done by sensing the amount of current sent to
the light source. In another embodiment, the processor has the
value of the amount of power that corresponds to the amount light
detected stored in the look-up table. If the sensed light is
greater than the first predetermined value, the amount of power to
the light source is reduced, as shown at block 119, corresponding
to the amount of the sensed light that is greater than the first
predetermined value. On the other hand, if the sensed light is less
than the second predetermined value, the amount of power to the
light source is increased, as shown at block 125, corresponding to
the amount of the sensed light which is less than the second
predetermined value. In an alternate embodiment, the light level is
adjusted, either upward or downward, by incrementing the current to
the light source upward or downward. This determination of the
light level in the optical path is preferably continuous when the
machine is in use.
[0096] In addition to controlling the intensity of the light
source, the spectral distribution of the light source should be
controlled in order to obtain the proper color-fidelity image.
Imaging systems, such as photographic film or cameras, have a
certain spectral distribution in which they best operate. In order
to obtain the best image from the imaging system, one must choose
the illumination from the light source in order to be within the
optimal spectral distribution of the imaging system. In addition,
analysis of specimens may be spectrally based. In those instances,
the correct spectral distribution removes potential error based on
varying illumination.
[0097] One measure of the spectral distribution is the color
temperature. The color temperature is a measure of the intensity of
the light at different wavelengths. Therefore, analysis of the
color temperature indicates the spectral distribution of the light
in the microscope. In an alternative embodiment, the spectral
distribution may be sensed at a band of wavelengths or across the
entire electromagnetic spectrum.
[0098] Typically, an incandescent light source shifts its spectral
distribution of the light (and hence its color temperature) when
the light source increases or decreases illumination. At the lowest
illumination levels, the majority of the incandescent light may be
in the infrared light range. As the illumination increases, the
peak of the wavelength shifts to the visible light range eventually
shifting to the ultraviolet light range.
[0099] In order to maintain proper illumination during operation of
the microscope, the proper illumination is determined during
initial calibration of the microscope. Also, during calibration,
measurements are taken at wavelengths to determine the proper
intensity at the wavelengths for the proper illumination.
Thereafter, during operation, the intensity is tested at the
wavelength(s) to determine whether the intensity of the light
source should be increased or decreased.
[0100] Referring to FIG. 4E, there is shown a diagram of a spectrum
distribution measurement system that measures color temperature.
The incoming light is sent to a dichroic beam splitter 141, which
splits the light into two parts with high efficiency. Other forms
of beam splitters may be used depending on the efficiency
necessary. The split beams are then sent to wavelength selection
filters 143, 145 whereby a narrow band of wavelengths are passed.
Thereafter, the filtered light is sent to Detector .lambda..sub.1
147 and Detector .lambda..sub.2 149 which generates a current (or
voltage depending on the sensing circuit) as a function in the
corresponding wavelength. Detector .lambda..sub.1 147 and Detector
.lambda..sub.2 149 in one embodiment are both photodetectors (e.g.,
diodes). In another embodiment, the selection filters and diodes
may be integrated into one package. Further, in a preferred
embodiment, the selection filters and detectors are placed closer,
and sense light closer, to the light source 77. In an alternate
embodiment, selection filters and detectors are placed closer to
the condenser lenses 63, 65 in order to sense any changes in the
spectral distribution as light travels through the microscope
system.
[0101] A graph of a spectral distribution of current (I) versus
wavelength (.lambda.) for two different illuminations is shown in
FIG. 4F. Referring to FIG. 4G, there is shown a flow chart for
determining and modifying the light level in the microscope system
to operate at a predetermined spectral distribution. The color
temperature is proportional to I.sub..lambda.1/I.sub..lambda.2.
Therefore, in order to determine the change in color temperature
(and hence spectral distribution), the present measurement of the
proportion is compared to the proportion measured during
calibration of the system (when the system was operating with an
optimal spectral distribution). The amount of light is sensed at
certain wavelengths, .lambda..sub.1 and .lambda..sub.2, as shown in
block 151. Depending on the amount of light sensed, currents are
generated in the detectors, as shown in block 153. Depending on the
comparison between the outputs of Detectors .lambda..sub.1 and
.lambda..sub.2, and a value which is determined during calibration,
the current or voltage of the light source is modified, in order to
maintain a constant color temperature (and hence constant spectral
distribution). For example, if .lambda..sub.1 is greater
.lambda..sub.2, and the current proportion of
I.sub..lambda.1/I.sub..lambda.2 is less than the calibrated
proportion (which is stored in the same look-up table, or similar
look-up table as the table 109 in FIG. 4C), as shown in block 157,
the spectral distribution is too far into the infrared range, so
the illumination should be increased (by increasing the voltage or
current), as shown in block 159. Likewise, if the current
proportion of I.sub..lambda.1/I.sub..- lambda.2 is greater than the
calibrated proportion, as shown in block 161, the spectral
distribution is too far into the visible region or ultraviolet
range, so the illumination should be decreased (by decreasing the
voltage or current), as shown in block 163. In this manner,
constant color temperature may be maintained in order to optimize
the use of the imaging system and maintain the integrity of
spectral-based analysis.
[0102] As discussed previously with respect to FIGS. 4A-4D, the
intensity of the light source may be controlled by varying the
current (or voltage) to the light source. The greater the intensity
desired, the higher the current (or voltage). However, when
attempting to integrate control of both intensity and spectral
distribution (or color temperature), means other than modifying the
intensity at the light source are used to control the intensity.
For example, one may separate the two functions by controlling the
color temperature through the adjustment of the lamp power and by
controlling the intensity by using crossed polarizers in the
optical path. Depending on the intensity required, the polarizers
may be turned to modify the intensity of the light. If polarized
light is not conducive to the imaging system, a polarizer scrambler
may be used in combination with the polarizers. Other means may be
used to shield a portion, or all, of the light in the optical path
without altering the power to the light source. Another method to
modify the intensity without influencing the color temperature is
through neutral density filters. Moreover, any means known to those
skilled in the art that does not influence the spectral
distribution or color temperature but affects the intensity may be
used.
[0103] In an alternate embodiment, a selection filter placed in
front of the detector 101 for the intensity illumination in FIG. 4A
may sense data both for color temperature and for intensity. The
single detector may sense the intensity at one wavelength. Assuming
a constant spectral distribution for a variety of intensities, both
the intensity and the color temperature may be determined.
Moreover, in an alternate embodiment, a wavelength selection means
72 which selectively passes a single wavelength or a band of
wavelengths may be placed anywhere the optical path.
[0104] Referring to FIG. 5A, in one embodiment of the invention
that is of particular utility in an automated system, there is
shown a fixed condenser geometry of an imaging system configuration
of the microscopic assembly, as used in the automated sample
analysis system 23 in FIG. 1B. In systems which are completely
automated, the optics are designed with fixed rigid optics that are
prealigned. During initial calibration of the microscope, the
placement of certain optics, including the condenser lens(es) and
the numerical aperture, are Therefore, once assembled, aspects such
as the focus, the diaphragm size, the aperture, etc. are fixed.
FIG. 5A is shown with the lenses all fixed in locations by a
condenser lens body 80. Once built, the lenses cannot change in
position.
[0105] In order to design a system that may be configured as a
fixed optic system, a portion of the optical system, as shown in
FIG. 4A may be designed with the fixed optics, as shown in FIG. 5A.
The optical system is reconfigured with lens focusing and pupil
apertures all established by machined and locked settings during
initial calibration of the microscope. This insures that the system
is always in the calibration established at the time of setup.
Referring to FIG. 5A, the condenser lenses 63, 65 in one embodiment
may be fixed rigidly to the microscope. Also shown is the objective
16, which is one type of magnification lens. Condenser lens 63 and
condenser lens 65 are placed within a housing 68, as shown in FIG.
5C, a predetermined distance apart using spacers 81 to maintain the
separation. In addition, numerical aperture 67 has a fixed pupil
and is held rigidly by abutting the numerical aperture 67 against a
ledge 86 and placing a snap ring 83 to hold the numerical aperture
67 (with a fixed aperture) rigidly in place. The ledge 86 may be
machined in order to properly align the numerical aperture 67
during calibration of the microscope. Another ledge 85 may be
machined in order to affix the assembly with the condenser lenses
63, 65 and numerical aperture 67. Mounting screws 88 are used to
adjust the fit, which is thereafter permanently affixed by pins 90,
as shown in FIG. 5A and 5B, so that condenser lens body 80 is
attached to the Z-axis plate 13. In this manner, the condenser
lenses 63, 65 and the numerical aperture 67 are permanently in
focus and do not require adjustment. Further, the field diaphragm
71 is fixed to the base, as shown in FIG. 2G, and has a fixed
pupil. In an alternative embodiment, for a light source that is not
attached to the base, the field diaphragm may be attached to a
portion of the microscope other than the base. However, the field
diaphragm still has a fixed pupil.
[0106] Imaging System
[0107] Referring to FIG. 6, there is shown a side view of a
microscope with an attached imaging system. In one embodiment, the
imaging system is a camera 127. The imaging system is affixed to
the microscope, according to one embodiment, at two separate
places. The first place is at the viewer portion of the microscope.
The camera mounts to an extender portion 129. The extender portion
129, in one embodiment, is L-shaped with one end being connected to
the camera via a screw thread C-mount 131 and the other end being
connected to the microscope via a dovetail portion 133. In
addition, the camera 127 is attached to the body of the microscope
at a second place along the upper microscope housing 138 of the
camera itself. Referring to FIG. 6, there is shown a second
connector, which, in one embodiment is a dovetail portion 135 that
is connected to one side of the camera 127. The second connector is
also connected to an intermediary piece 137, such as a shim. The
intermediary piece is connected to the body of the microscope. In
this arrangement, the camera is first aligned via the extender
portion 129 and thereafter the camera body is rigidly fixed to
mounting surfaces provided on the microscopy frame. The camera is
therefore rigidly fixed to the microscope so that during operation,
the camera will not be moved out of alignment. The camera may be
rigidly fixed to the microscope in more than two places.
[0108] Connection to External Systems
[0109] Moreover, according to a preferred embodiment, the
microscopy system is designed to be integrated into a larger system
containing additional components. The microscopy system includes
mounting geometry and electrical connections sufficient to allow
incorporation into other instruments. The imaging system may
therefore be designed to minimize problems with interconnections to
other devices such as computers and the like. The imaging system
includes a connector 62, as shown in FIGS. 2A and 2C. The system is
designed with a centralized circuit board 64 which, in turn, is
connected to the connector 62. The connector 62 provides data
transmission to such components as the DMS discussed above as well
as electrical connections. The system may also have fixtures with
mounting surfaces for the placement of accessories (such as a laser
bar code reader). The added structure provided by these fixtures
enhances the stability and thus the accuracy of the system. As
shown in FIGS. 2A and 2C, there are ports 66 that provide a
connection for all of the on-board systems for the microscope. The
ports 66 allow for the connection to other units that may work in
combination with the microscope. For example, other devices, such
as a dotter, bar-code reader, power lens turret controller, slide
sensor and camera controller, etc. may be in communication with the
microscope and imaging system via the ports 66, for instance.
[0110] Bridge Frame
[0111] The microscope assembly described above advantageously
provides for increased stability and precision. In the arrangements
described above, however, the microscope frame structure is
illustrated as a "C" frame or cantilevered design, which is
primarily dictated by a need to provide operator access to the
specimen from the front of the microscope, effectively through the
open side of the "C" structure. Unfortunately, when a microscope is
used for quantitative imaging operations, it has now been
determined that the instability of the cantilevered design begins
to limit the efficacy of the system. Movement caused either within
the system (such as vibrations caused by a motor within the
microscope) or outside the system (building shaking or heating/air
conditioning system) effect the operation of a typical cantilevered
system. In particular, this type of structure does not have a good
dynamic stiffness. Dynamic stiffness is a measure of the dynamic
response of the microscope (i.e., a measure of how the microscope
reacts to live loads such as how much the microscope shakes,
vibrates or deflects). Microscopes which magnify an image to a
great degree should have a sufficiently good dynamic stiffness,
particularly at the optical center line. Otherwise, the microscope
will shake or move to such an extent that the microscope will not
be able to capture a clear image. However, the current "C"
structure allows for too much variations, especially at the optical
center line, limiting the ability of the imaging system to realize
the maximum resolving power of the sensing elements.
[0112] According to an additional aspect of the invention,
microscope stability can be further enhanced by including structure
which increases the dynamic stiffness of the microscope with a
focus on the dynamic stiffness at the optical center line. One
example of the structure is shown in FIGS. 7 and 8. Referring to
FIGS. 7 and 8, a brace 200 is rigidly connected between the upper
portion 210 of the microscope assembly and lower portion 212 of the
microscope assembly, thereby making the overall microscope frame
structure a closed ring (from a side view). The brace 200 is
designed to work in conjunction with the upper portion 210 of the
microscope assembly to make the microscope more stable during
operation. In turn, rather than mounting optical elements (such as
a camera, for instance) on top of a cantilevered structure, the
optical members are instead preferably mounted at the center on
what is effectively a "bridge" structure, supported on one end 214
by the brace and on another end 216 by the "back" side of the
microscope frame. In the exemplary embodiment, these supporting
structures on both sides of the optical element carrier (i.e., the
bridge) have substantially the same tensile and compressive
characteristics as each other, thereby enhancing stability.
[0113] The structure of brace 200 is designed to afford the
requisite stability. The brace 200 should be close to the optical
center line, without interfering with the movement of the stage in
either the z-direction or y-direction. To accomplish this, the
brace 200 is composed of two portions, lower portion 218 and upper
portion 220. Lower portion 218 meets upper portion 220 at surface
222. The innermost portion of surface 222 is point 224 which is
adjacent to the stage, but not touching the stage, when the stage
is in its outermost position (i.e., the stage is in its uppermost
z-position and in its greatest y-position).
[0114] Moreover, the cross-sectional area of the brace 200 is
designed to afford the requisite stability. This is due to the fact
that the corresponding microscope structure without the brace was
exhibiting movement only in the z-direction. To provide additional
stability in the z-direction, the brace has a rectangular
cross-section, as shown in FIGS. 7 and 8. Alternatively, if the
microscope exhibits movement in the z-direction and x- or
y-directions, the cross-section of the brace is correspondingly
modified in order to provide stability in each direction. For
example, if there is vertical (z-direction) and lateral (x- and/or
y-direction) movement, the cross-section of the brace may be
composed of a "T" shape with the top portion of the "T" providing
stability in the lateral direction. Alternatively, the
cross-section of the brace 200 may be a hollowed section.
[0115] In order to empirically determine the shape of the
cross-section of brace 200, measurements are first taken of the
deflection of the microscope without brace 200. Varying weights
(e.g., 1 lb, 5 lb, 10 lb, etc.) are placed on the upper portion 210
of the microscope (without the turret and eyepiece portion) at the
optical center line. In a preferred embodiment, the amount of
deflection of the upper portion 210 of the microscope is measured
point 226, as shown in FIG. 8. However, the amount of deflection
can be measured at any point along the optical center line. Based
upon these measurements, calculations are made to determine the
thickness of the brace.
[0116] This arrangement affords a maximum stiffness consistent with
the mass and modulus of the supporting material. In fact, this
overall bridge frame arrangement is believed to increase stability
by over one order of magnitude (compared to the microscope frame
without brace 200). For example, in one measurement, the amount of
deflection was 20 .mu.m without brace 200 and with a representative
weight, while the amount of deflection with brace was less than 1
.mu.m. Further, while brace 200 may somewhat block front access to
the stage of the microscope system and to a specimen residing on
the stage, such access is of decreased importance in automated
imaging and screening systems, since it is rarely necessary for an
operator to manually move the specimen on the stage. Nevertheless,
in an alternative arrangement, the arrangement of FIG. 7 could be
varied to provide a plurality of braces from upper portion 210 to
lower portion 212, or to provide a single brace with a front
opening for operator access. In still an alternate embodiment, the
supporting structure may be composed of an upper section of a
sphere, with a hole in the top of the upper section where the
optical center line passes through the turret.
[0117] In the exemplary embodiment, the connecting brace is cast as
a loose piece and is then bolted to bosses that are integrally cast
at the upper and lower portions of the basic "C" frame. The
connecting brace is preferably cast of the same material as the
rest of the microscope frame, so that it has the same thermal
expansion and contraction characteristics. In the exemplary
embodiment, this material is an aluminum alloy. Alternatively, the
brace could be cast as an integral part of some or all other
portions of the microscope frame.
[0118] Dual Plate
[0119] As described above, with respect to FIG. 3B for instance,
the microscope system of an exemplary embodiment may include a
Z-axis plate 13 from which three guideposts 55 extend into
interference fit with bushings 54 that are attached to base 12.
This arrangement provides for increased stability and accurate
vertical movement of stage 27. However, if the guideposts are
rigidly fixed only to the underside of the Z-axis plate, there is
still a possibility that the structure might sway under some
conditions. Moreover, if the elevating screw is in direct contact
to the underside of the Z-axis plate, movement in the lateral
direction is possible. Specifically, while the elevating screw is
designed to direct force in the z-direction, unwanted force in the
x- and/or y-direction is possible due to misalignment of the
elevating screw.
[0120] To help minimize this possibility, still another alternative
arrangement can be provided, as illustrated in FIG. 9A. Referring
to FIG. 9A, an additional plate 216 is provided, fixed rigidly to
the guideposts 55 preferably underneath the bushings. This lower
plate functions to increase the stability and stiffness of the post
and plate structure, effectively creating an open box out of
arrangement, and is believed to increase stability significantly.
As shown in FIGS. 9A and 9B, the Z-axis plate 13 and the lower
plate 216 are rigidly affixed to one another by guideposts 55 and
by a spacer post 230. Ball bushings 54, which are affixed to the
base 12, run in an interference mode with the guideposts 55. As
shown in FIGS. 3A-C, the ball bushings 54 are placed below the
Z-axis plate 13. For additional stability, additional ball bushings
54 are placed directly above the lower plate 216. In the lowermost
setting of the Z-axis plate, the distance 236 between the upper
ball bushings and the Z-axis plate is minimal. Likewise, in the
uppermost setting of the Z-axis plate, the distance between the
lower ball bushings and the lower plate is minimal. This is to
increase the stability throughout the movement of the Z-axis
plate.
[0121] The spacer post 230 is affixed to the Z-axis plate via a
screw 232 and affixed to the lower plate 216 by a press-fit in an
opening 238 in the lower plate 216. The spacer post 230 is
positioned directly above the elevating screw 89, with a nub 234 on
the top of the elevating screw 89 fitting in the lower portion of
the spacer post 230. The spacer post 230 serves two functions.
First, it increases the rigidity of the entire Z-axis plate/lower
plate structure, thereby improving its dynamic stiffness. Second,
it serves as a rigid structure which may translate the
upward/downward movement of the elevating screw 89 to the Z-axis
plate 13 and keep the Z-axis plate 13 parallel to the lower plate
216. In a previously described embodiment, the elevating screw 89
is in contact with one of the guideposts 55 (as shown in FIGS. 3A
and 3B) so that the upward force of the elevating screw is
translated through the guidepost to the Z-axis plate 13. However,
the current design allows for additional stability since the spacer
post 230 is rigidly affixed at both of its ends (as opposed to the
previous design which rigidly affixed the guidepost at only one
end). In a preferred embodiment, a single spacer post is used. In
an alternate embodiment, a plurality of spacer posts may be placed
in between the Z-axis plate 13 and the lower plate 216.
[0122] As discussed previously, the elevating screw 89 may have
unwanted movement in the lateral direction. Because it is very
difficult to make the elevating screw micron perfect (i.e.,
eliminating the lateral movement in the elevating screw 89), the
present design minimizes its effects on the examination of the
sample. The present design includes contacting the elevating screw
with the lower plate rather than the Z-axis plate 13. Therefore,
any lateral movement is felt by the lower plate 216 but not
translated to the Z-axis plate 13. Specifically, because of the
rigidity of the Z-axis plate/lower plate structure and because of
the guideposts 55 and ball bushings 54, the lateral movement is not
translated to the Z-axis plate 13 (upon which the sample sits and
where focusing is performed). Thus, the current design allows for
increased stability.
[0123] The lower plate 216 is "C" shaped and composed of the same
material as the Z-axis plate 13. The shape of the lower plate is
216 is dictated by the optical path in the microscope system. The
light travels from the light source, though the open side portion
of the "C" shaped lower plate 216, and reflected upward through the
Z-axis plate 13. Moreover, as discussed previously, the guideposts
55 are affixed to the Z-axis plate 13 by an adhesive. In a
preferred embodiment, the guideposts 55 are affixed to the lower
plate 216 via collars 228. The collars 228, as shown in FIG. 9C,
have a guidepost opening 240, a slit 242 and screw openings 243.
The collars 238 are affixed to the underside of the lower plate 216
by slipping the collars 228 through the guideposts 55 via the
guidepost opening 240, placing a screw 244 through the slit 242 of
the collars (to hold the collars securely to the guideposts 55),
and placing screws 246 through the collar (to hold the collar to
the underside of the lower plate 216).
[0124] Referring to FIG. 10, there is shown an apparatus for
providing upward and downward force. Similar to the elevating screw
shown in FIGS. 2A and 3B, the apparatus includes a pulley which
engages the top portion of a nut. The nut 87, via a collar 250, is
in contact with the inner race of radial bearings 57. The outer
race of the radial bearings 57 is in contact with the base 12 (so
that the outer race does not move). The nut 87 contacts the
elevating screw 89 via ball bearings 248. During operation, the
pulley 61 exerts force on the nut 87 thereby turning the nut 87.
Because of the radial ball bearings 57, the nut 87 does not move
upward/downward. The radial movement of the nut 87 is translated
into an upward/downward movement of the elevating screw 89. For
additional stability, thrust bearings 252 are added at the lower
portion of the apparatus. The inner portion of the thrust bearings
252 is in contact with the collar 250 and the outer portion is in
contact with the base 12 (so that the outer portion does not move).
The thrust bearings 252 complement the column design of the z-axis
elevating screw drive, making the drive less compressible and
stabilizing the drive in the thrust direction. Thus, through the
use of the radial bearings 57 and the thrust bearings 252, the nut
is more secure during movement, so that the elevating screw is
likewise more secure.
[0125] Rotating Wheel
[0126] As described above, the microscope system includes a lamp
for illuminating the sample. Specific frequencies of illumination
are desired depending on the operation of the microscope. In order
to filter out the unwanted frequencies, a motorized rotating filter
wheel mechanism 254 is designed into the microscope frame. This
mechanism 254 is located in the illumination system path just after
the lamp collector lens and heat shield system, as shown in FIG.
11A. It is positioned before the field iris diaphragm. Locating the
filter mechanism in this location has the following benefit of
illuminating the specimen with only the specific wavelength light
desired and not the broad spectrum. This has certain advantages in
some forms of the quantifiable imaging systems. An additional
benefit is the reduction in the amount of vibrations. Because the
filter mechanism uses a motor as the prime mover, the vibrations
caused by the motor and the moving mass do not have a negative
effect on the stability of the camera system. Because the motorized
rotating filter wheel is (1) located far from the camera (relative
to other components in the microscope) and (2) in the base
component, the most stable component of the system, so that the
wheel does not appreciably affect the operation of the camera. In
one embodiment, the rotating wheel has 6 slots 256, as shown in
FIG. 11B. The wheel 254 rotates so that filters placed in the slots
256 modify the spectrum of light in the optical path.
[0127] An exemplary embodiment of the present invention has been
described herein. It is to be understood, of course, that changes
and modifications may be made in the embodiment without departing
from the true scope and spirit of the present invention, as defined
by the appended claims.
* * * * *