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Method and apparatus for microphotometering microscope specimens

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USRE34214E
USRE34214E US07288287 US28828788A USRE34214E US RE34214 E USRE34214 E US RE34214E US 07288287 US07288287 US 07288287 US 28828788 A US28828788 A US 28828788A US RE34214 E USRE34214 E US RE34214E
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specimen
light
plane
part
focal
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US07288287
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Kjell S. Carlsson
Nils R. D. Aslund
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Integenx Acquisition Corp
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Integenx Acquisition Corp
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    • GPHYSICS
    • G02OPTICS
    • G02BOPTICAL ELEMENTS, SYSTEMS, OR APPARATUS
    • G02B21/00Microscopes
    • G02B21/0004Microscopes specially adapted for specific applications
    • G02B21/002Scanning microscopes
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using infra-red, visible or ultra-violet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/59Transmissivity
    • G01N21/5907Densitometers
    • G01N21/5911Densitometers of the scanning type
    • GPHYSICS
    • G02OPTICS
    • G02BOPTICAL ELEMENTS, SYSTEMS, OR APPARATUS
    • G02B21/00Microscopes
    • G02B21/0096Microscopes with photometer devices
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using infra-red, visible or ultra-violet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47Scattering, i.e. diffuse reflection
    • G01N21/4738Diffuse reflection, e.g. also for testing fluids, fibrous materials
    • G01N21/474Details of optical heads therefor, e.g. using optical fibres
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using infra-red, visible or ultra-violet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N21/645Specially adapted constructive features of fluorimeters
    • G01N21/6456Spatial resolved fluorescence measurements; Imaging
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00Features of devices classified in G01N21/00
    • G01N2201/10Scanning
    • G01N2201/108Miscellaneous
    • G01N2201/1087Focussed scan beam, e.g. laser

Abstract

A method of microphotometering individual volume elements of a microscope specimen 10, comprising generating a luminous dot or cursor and progressively illuminating a plurality of part elements in the focal plane 11 of the microscope through the specimen. The mutual position between the specimen and the focal plane is then changed and a plurality of part elements in the focal plane are illuminated. Reflected and/or fluorescent light and transmitted light respectively created by the illumination is collected, detected and stored for generating a three-dimensional image of that part of the specimen composed of the volume elements. Illumination of multiples of part elements is implemented by deflecting the cursor and/or by moving the specimen. The change in the relative mutual position between the specimen and the focal plane of the microscope is effected either by displacing the specimen or the objective. Apparatus for carrying out the method include a specimen table 301, a microscope objective and light source 31-32-33. The table or the objective are arranged for stepwise movement along the main axis of the microscope synchronously with punctilinear light scanning of the specimen. The table is arranged for stepwise movement at right angles to the main axis and/or the light source is arranged for deflection over the focal plane 21 through the specimen.

Description

TECHNICAL FIELD

The invention relates to a method for microphotographing prepared specimens and displaying the resultant images thereof, by generating with the aid of a convergent light beam a luminous dot or cursor in the focal plane of a microscope, matching the cursor with a plurality of part elements in the prepared specimen, collecting the light created by the cursor and the prepared specimen, detecting the collected light, and generating corresponding electric signals. The invention also relates to apparatus for carrying out the method.

BACKGROUND ART

Qualitative and quantitative microscopic investigations (study assays) of prepared specimens of the human body and of animals constitute an important and time-consuming part of research work, for example, within the field of medicine. For example, when wishing to make a close study of a liver there is first prepared a given number of thin specimens of the liver to be examined (these specimens being prepared with the aid of a microtome), whereafter the specimens are subjected to a qualitative and quantitative examination under a microscope. A picture of the general condition of the liver, changes in its state of disease, etc., can then be obtained by combining the results of the assays.

It is also known to obtain the assay result from a plurality of locations on the surface of a microscope specimen with the aid of electronic scanning techniques.

When applying known techniques it is still necessary in general to prepare a relatively large number of specimens (sections) from the subject to be examined, which is expensive, time-consuming and highly laborious. The object of the present invention is to simplify and, in many instances, even to refine the methodology of effecting such microscopic investigations, and at less cost.

SUMMARY OF THE INVENTION

The method according to the invention comprises producing a three-dimensional image of a volume of a microscope specimen (i.e. a specimen for microscopic study) taking a starting point from the method described in the introduction, and is mainly characterized by changing the mutual relative positions of the specimen and the focal plane and renewed matching of the cursor or luminous dot with a plurality of part elements in the specimen; collecting light created by the cursor and part elements in the specimen; and screening-off any synchronous disturbing light created by adjacent (above, beneath, beside) part elements in the specimen; detecting the light thus collected and storing the measurement values resulting from said detection, the storage of the measurement values being effected synchronously with the matching of the cursor with the part elements in the specimen and the change in the relative mutual positions of the specimen and the focal plane, the measurement values being representative of locations in various layers through the specimen; and collecting the measurement values derived from locations in a plurality of layers representative of a given volume of the specimen in dependence upon upon planned/desired analysis of the specimen.

The aforesaid measurement values together give a detailed description or picture of the whole of the volume determined through all of said plurality of locations. By converting the measurement values to digital form and storing the same in the memory of a data processor, it is possible to produce three-dimensional images suitable for assay and further analysis.

Thus, it is possible--without preparing fresh physical specimens--to study the specimen on a data screen from different projections and to combine two such projections to obtain a stereoscopic image. This enables the person carrying out the investigation to produce in a very short time precisely those views and incident angles which may be desired as the investigation proceeds.

The study of nerve cells is an example of an area in which the method according to the invention is particularly well suited. Nerve cells exhibit an extremely large number of branches and present a complicated three-dimensional structure. Investigatory studies of such structures with the aid of traditional microscope equipment are extremely difficult to carry out and are also very time-consuming. In addition the information obtained therefrom is incomplete. Corresponding studies carried out in accordance with the invention have been found to provide abundantly more information than that obtained when carrying out the studies in accordance with known methods. Other possible areas where the three-dimensional structure is of great interest include studies of the inner structures of cells, for example a study of the configuration of the cell core, chromosomes etc.

The illumination and registration technique according to the invention affords the following advantages. It is possible to select a thin section from the specimen for registration and to combine several such sections to produce a three-dimensional image. The images are made richer in contrast and clearer by decreasing the level of stray light. Sensitive and delicate specimens are protected from harm, because the total light exposure is low.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will now be described in more detail with reference to the accompanying schematic drawings, in which

FIG. 1 illustrates in perspective the contour of a specimen and a section laid through the specimen;

FIG. 2 is a vertical sectional view of a specimen with a section according to FIG. 1 laid in the surface structure of the specimen;

FIG. 3 illustrates apparatus for microphotometering a microscope specimen while using reflected and/or fluorescent light, comprising a two-dimensional scanner and a vertically movable object table;

FIG. 4 illustrates the apparatus according to FIG. 3 modified with a single-dimension scanner and a vertically and laterally adjustable table;

FIG. 5 illustrates the apparatus according to FIG. 3 which lacks the scanner but has an object table which can be moved in three dimensions;

FIG. 6 illustrates the apparatus according to FIG. 5 modified for transmitted or fluorescent light; and

FIG. 7 illustrates a specimen in which a plurality of sections have been laid.

DETAILED DESCRIPTIONS OF THE PREFERRED EMBODIMENTS

In FIG. 1 the reference 10 identifies a microscope specimen through which there is laid an imaginary horizontal section comprising a plurality of part elements: for reasons relating to the technicalities of the drawing the section exhibits 20 rows in the x-direction and 15 rows in the y-direction, i.e. a total of 300 part elements, such as part elements 12 and 13 for example, but may in practice of course exhibit many more or far less elements and with sections of a different form, such as square or elongated rectangular sections for example, depending entirely upon the form of the specimen.

When microphotometering a microscope specimen, 75, 100 or may be 200 such imaginary sections may be envisaged in practice, these sections being plane parallel and bordering upon one another, two and two, or spaced equidistantly from one another. That part of the section 11 which lies within the specimen 10 has been shown in the figure with a thicker line 14.

The specimen 20 illustrated in vertical sections in FIG. 2 constitutes part of a material surface to be studied. A section 21, corresponding to the section 11 in FIG. 1, is placed in the upper part of the specimen and is thus here seen from the side. The two indicated sections 11 and 21 are representative of what is referred to hereinafter as "the focal plane".

The apparatus illustrated in FIG. 3 includes a microscope 30 having an object table 301, a laser-light source 31 for producing a beam of light through a beam-splitting unit 32, and a scanner 33 operative in panning the beam of light to a plurality of locations in the focal plane (x-y-plane) of the microscope 30, an aperture 34, and a control and data-collection assembly 36 for controlling, inter alia, the scanner 33 via a line 361, and for collecting electric signals deriving from reflected and/or fluorescent light arriving at the detector 35 after having passed from the object table 301 through the microscope 30, the scanner 33 and the aperture 34, this light being converted in the detector 35 to electric signals which are transferred through the line 351 to the control assembly 36, and finally externally located equipment for storing, processing and visually displaying data originating from said signals, this equipment comprising a data processor 37 and an auxiliary store 38, and a display screen 39 connected to the data processor 37.

A luminous dot or cursor created by the light beam from the laser source 31 is deflected by the scanner 33 to a number of positions in a specimen placed on the object table 301, in the focal plane, which focal plane may be the section indicated in FIG. 1. Stray light, possibly eminating from locations (volume elements) above, beneath or beside the location in the x-y-plane just scanned by the scanner 33, is excluded by the aperture 34 and is caused to deliver information relating to its characteristics through, for example, reflected light. When a location has been scanned a control pulse is delivered from the control assembly 36 to the scanner 33, via the line 361, and the scanner therewith reflects the beam to the next location (e.g. an x-square) in the same row (y-row), this procedure being continued until the whole of section 11 has been scanned or sensed. The object table 301 is thereupon moved stepwise (up or down) in response to a control pulse (signal) fed from the control assembly 36 to a drive unit 363 via the line 362, which drive unit guides directly movement of the table 301 is the z-direction. The object table with the specimen thereon is thus displaced through a given distance in the z-direction, whereupon the focal plane of the microscope 30 will obtain a new position through the specimen, this new position being scanned in the same manner as that previously described. The whole of the specimen is thus scanned in this way successively at equidistant locations along equidistant parallel lines in equidistant planes. Signals are transferred from the scanner 33 and the drive unit 363 respectively to the controller assembly 36, bearing information relating to the current position of the cursor created by the light beam (x-y-direction) and of the table 301 (z-direction).

When creating a three-dimensional picture of a volume of a microscope specimen with the aid of the apparatus just described, the following operational steps are taken:

a luminous dot or cursor is created in the focal plane 11 of the microscope 30, this plane passing through the specimen;

the cursor is deflected to a plurality of locations in the focal plane 11;

the mutual relative positions of the specimen and the focal plane 11 are changed and deflection of the cursor to a plurality of locations in the focal plane is renewed;

the change in the relative mutual positions of the specimen and focal plane is repeated stepwise, and after each such change the luminous cursor is again deflected to a number of locations in the focal plane;

the light created by the luminous cursor and part elements of the specimen is collected, this light carrying information relating to locations in the specimen, and any disturbing light eminating synchronously from adjacent locations is screened-off; and

the thus collected light is collected and the measurement values obtained through said detection are stored, the storage of the measurement values being effected synchronously with the deflection of the luminous cursor in the focal plane and with the change in the mutual position between the specimen and the focal plane.

In this way there is obtained a description or picture of the whole of the volume of the specimen comprising the individual volume elements (the locations), this being achieved in an extremely short period of time. By way of example it can be mentioned that when microphotometering a specimen through approximately 100 sections and having 2562 measurement values (locations) in each section, the actual apparatus time is approximately 10 minutes. In addition to the highly simplified preparation of the specimen, however, it is also possible to produce through the data processor 37 three-dimensional images with selectable projection directions and with the possibility of making volumetric measurements.

The apparatus illustrated in FIG. 4 coincides with the apparatus illustrated in FIG. 3 with the exception that deflection caused through the scanner 43 is effected only in one direction (e.g. the y-direction), while the object table 401 is moved stepwise in the horizontal direction (x-direction) subsequent to the light beam having been advanced along a whole row or line and been displaced stepwise in a vertical direction (z-direction) subsequent to the light beam having been advanced along a whole section. This modification may be suitable when studying specimens of substantially elongated rectangular shape.

When the aforegiven exceptions in the functioning of the apparatus, the corresponding circuits and devices illustrated in FIGS. 3 and 4 are identified by reference numerals differing only in their first digits.

The apparatus illustrated in FIG. 5 coincides with that illustrated in FIG. 3 with the exception that the scanner 33 is omitted totally and the object table 501 is instead arranged to be moved stepwise along a surface in the horizontal plane (x-y-plane) and stepwise in a vertical direction (z-direction). These movements are controlled from the drive unit 563 which receives, in turn, synchronizing pulses from the control assembly 56.

Mutually corresponding circuits and devices in FIGS. 3 and 5 are identified by reference numerals differing only in their first digits.

The apparatus according to FIGS. 3-5 are intended to utilize reflected and/or fluorescent light from the specimen. It is also possible to work with transmitted light, however, and the apparatus illustrated in FIG. 6 is intended for this case. Light from the laser 61 passes the microscope 60 and is focused on a point in the focal plane in a specimen placed on the object table 601. The light allowed to pass through or excited (fluorescence) by the specimen at the point in question is collected by an objective 602 and permitted to pass an aperture 64 and, in the case of fluorescence, a filter 603 to eliminate exiting laser light, whereupon detection is effected in the detector 65 (conversion to electric signals and analogue/digital conversion) and collection in the control and data collecting assembly 66 in the aforedescribed manner. In a manner similar to that described with reference to FIG. 5, the object table 601 is also caused to move stepwise, in response to control signals from the assembly 66, along a line or row in a surface plane (x-y-plane) and in a direction (z-direction) perpendicular to the surface plane. The function of the apparatus is similar in other respects to the function of the previously described apparatus.

The various remaining circuits or devices in FIG. 6 corresponding to the circuits or devices in FIG. 5 are identified by reference numerals differing only in their first digits.

The invention is not restricted to the aforedescribed and illustrated embodiments. For example, although the methods forming the basis for the apparatus illustrated in FIGS. 3 and 4, see also the following claims 2 and 3, probably give optimal results in respect of reflected light, modifications can be made in principle for the use of transmitted light. In addition, the drive units 363, 463 and 563 of respective apparatus according to FIGS. 3--5 can also be used to advantage for controlling movement of the microscope objective in z-directions instead of respective object tables 301, 401 and 501. There is obtained in both instances (fixed objective, movable object table in z-direction; movable objective in z-directions, fixed object table in z-directions) a change in the mutual distance between the specimen 10 and the focal plane 11.

In the aforegoing mention has been made as to how the light beam is stepped forward along a line on (in) the specimen with the aid of control signals from the control assembly (e.g. 36 in FIG. 3). Modifications may be made, however, to enable the light beam to be swung continuously forwards and backwards for example, but so that detection of the reflected signal takes place exactly at moments in time corresponding to given positional locations in the focal plane in the specimen.

It has been mentioned in the aforegoing that images in selectable projections can be readily obtained once the specimen has been microphotometered in accordance with the invention.

FIG. 7 illustrates schematically a specimen 10 through which sections 1-n have been laid (at right angles to the plane of the drawing) in accordance with the invention. A researcher who during the course of his/her work finds that he needs to view a section through a given part of the specimen from a different angle, e.g. through sections 70--70, is able to immediately obtain from the measurement value equipment an image comprised of measuring results from a plurality of sections 1-n, and with a starting point from this view image can then find reason to concentrate his/her interest to another part of the specimen, perhaps along an additional section. The possibilities are manifold and afford a high degree of flexibility in respect of research work.

Claims (15)

I claim:
1. A method for microphotometering and subsequent image combination by generating with the aid of a convergent light beam a luminous dot or cursor in the focal plane (11) of a microscope (30), fitting the cursor to a plurality of part elements in the specimen (10), and collecting light created by the luminous cursor and the specimen (10), detecting the collected light and producing corresponding electric signals, characterized by changing the mutual position between the specimen (10) and the focal plane (11) and re-fitting the luminous cursor to a plurality of part elements in the specimen (10); repeating stepwise changes in the mutual position between the specimen (10) and the focal plane (11) and, subsequent to each such change, again fitting or matching the luminous cursor to a plurality of part elements in the specimen; collecting the light created by the luminous cursor and part elements in the specimen (10) and screening-off any disturbing light created synchronously from adjacent (above, beneath, beside) part elements in the specimen (10); detecting the thus collected light and storing measurement values obtained through said detection, said storage optionally being effected synchronously with the matching of the luminous cursor with part elements in the specimen (10) and with the changes in the mutual position between the specimen (10) and the focal plane (11), said measurement values being representative of locations in various layers through the specimen; and combining the measurement values from locations in a plurality of layers, representative of a given volume of the specimen, in dependence upon a planned/desired analysis of the specimen.[...]. .Iadd.in a manner yielding a projected representation from a desired angle of at least a portion of the specimen. .Iaddend.
2. A method according to claim 1, characterized in that matching of the luminous cursor with a plurality of part elements in the specimen (10) is effected by .[.delinking.]. .Iadd.deflecting .Iaddend.stepwise the convergent light beam in two dimensions (x- and y-directions); and in that the stepwise change in the mutual position between the specimen (10) and the focal plane .[.(10).]. .Iadd.(11) .Iaddend.of the microscope is effected by moving stepwise the microscope object table (301) on which the specimen is placed (z-direction).
3. A method according to claim 1, characterized in that matching of the luminous cursor with a plurality of part elements in the specimen (10) is effected by relative rapid stepwise deflection of the convergent light beam in one dimension (y-direction), and by relatively slow stepwise displacement of the microscope object table (401) on which the specimen (10) is placed in a further dimension (x-direction); and in that the stepwise change in the mutual position between the specimen (10) and the microscope focal plane .[.(10).]. .Iadd.(11).Iaddend.is effected by stepwise displacement of the microscope object table (401) (z-direction).
4. A method according to claim 1, characterized in that matching of the luminous cursor with a plurality of part elements in the specimen (10) is effected by stepwise displacement of the microscope object table (501) along a surface (x-y-plane) perpendicular to the main axis of the microscope; and in that the stepwise change in the mutual position between the specimen (10) and the focal plane of the microscope (50) is effected by stepwise displacement of the object table (501) of the microscope (50) (z-direction).
5. A method according to claim 4, characterized in that collection of light (reflected fluorescent light) created by the luminous cursor and part elements in the specimen (10) is effected on that side of the object table (501) on which the microscope (50) is placed.
6. A method according to claim 5, characterized in that collection of light (transmitted light) created by the luminous cursor and part elements in the specimen (10) is effected on the opposite side of the object table (661) to that on which the microscope (60) is placed.
7. Apparatus for the microphotometering and subsequent image combination of a specimen, comprising a microscope (30) having an object table (301), a light source (31-32-33), a detector (35) and a control and data-collecting assembly (36), characterized in that the object table (301) of the microscope (30) is arranged for stepwise movement in a direction corresponding to the main axis (z-direction) of the microscope (30), said movement being controlled and effected in response to guide pulses from the control and data-collecting assembly (36) in synchronization with the scanning of the light source (31-32-33) of part elements in a microscope specimen (10) placed on the object table (301); and in that the apparatus also includes .[.equipment.]. .Iadd.means .Iaddend.(37, 38,39) for storing, processing and visually displaying data originating from said measurement values.[...]. .Iadd.in a manner yielding a projected representation from a desired angle of at least a portion of the specimen. .Iaddend.
8. Apparatus according to claim 7, characterized in that the object table (401) of the microscope (40) is arranged for stepwise movement in a first direction (x-direction) at right angles to the main axis of the microscope (z-direction); in that the light source (41-42-43) is arranged to scan stepwise part elements in the specimen in a further direction (y-direction) at right angles to the main axis of the microscope (z-direction); and in that movements of the object table (401) and the light source (41-42-43) are co-ordinated for scanning a first plurality of part elements in a first plane through the specimen, and then of a second plurality of part elements in a second plane through said specimen, said second plane extending plane parallel with the first plane, etc. for scanning the whole specimen.
9. Apparatus according to claim 7, characterized in that the object table (501) of the microscope (50) is arranged for relatively slow stepwise movement in a first direction (x-direction) at right angles to the main axis (z-direction) of the microscope (50) and in a relatively rapid stepwise movement in a further direction (y-direction) at right angles to the main axis (z-direction) of the microscope, wherewith movements of the object table (501) in planes at right angles to the main axis of the microscope and parallel with the main axis are co-ordinated through control pulses from the control and data-collecting assembly (56) for scanning part element after part element through the whole of the specimen. .Iadd.
10. A method for microphotometering a 3-dimensional specimen using a light detection apparatus, the specimen defining a plurality of layers, each layer defining a plurality of part elements, and the detection apparatus defining a focal plane, the method comprising the following steps:
(a) generating a cursor of light in the focal plane;
(b) positioning at least one of (1) the focal plane and (2) the specimen such that a desired one of the layers lies in the focal plane;
(c) selecting at least one of the part elements in the selected layer;
(d) positioning at least one of (1) the cursor and (2) the specimen to illuminate by means of the cursor the selected part element;
(e) screening-off unwanted light from part elements adjacent the selected part element;
(f) detecting light from the selected part element;
(g) producing signals indicative of predetermined characteristics of the detected light;
(h) storing representations of the signals;
(i) repeating selected ones of steps (a)-(h) a desired number of times; and
(j) analyzing the representations of the signals to produce measurements of the specimen representative of at least one 3-dimensional characteristic of at least a portion of the specimen. .Iaddend. .Iadd.
11. The method of claim 10 wherein the measurements produced in step (j) are volumetric measurements. .Iaddend. .Iadd.12. The method of claim 10 wherein the measurements produced in step (j) are surface area measurements. .Iaddend. .Iadd.13. The method of claim 10 wherein the measurements produced in step (j) are light intensity measurements.
.Iaddend. .Iadd.14. The method of claim 10 wherein the measurements produced in step (j) are distance measurements. .Iaddend. .Iadd.15. The method of claim 10 wherein the measurements produced in step (j) are angular measurements. .Iaddend. .Iadd.16. The method of claim 10 wherein the measurements produced in step (j) are surface parameter measurements.
.Iaddend. .Iadd.17. A method for microphotometering a 3-dimensional specimen using a light detection apparatus, the specimen defining a plurality of layers, each layer defining a plurality of part elements, and the detection apparatus defining a focal plane, the method comprising the following steps:
(a) generating a cursor of light in the focal plane;
(b) positioning at least one of (1) the focal plane and (2) the specimen such that a desired one of the layers lies in the focal plane;
(c) selecting at least one of the part elements in the selected layer;
(d) positioning at least one of (1) the cursor and (2) the specimen to illuminate by means of the cursor the selected part element;
(e) screening-off unwanted light from part elements adjacent the selected part element;
(f) detecting light from the selected part element;
(g) producing signals indicative of predetermined characteristics of the detected light;
(h) storing representations of the signals;
(j) repeating selected ones of steps (a)-(h) a desired number of times; and
(j) analyzing the representations of the signals to produce a projected representation from a desired angle of at least a portion of the specimen.
.Iaddend. .Iadd.18. The method of claim 17 wherein the projected representation is a 2-dimensional representation of a portion of the specimen bordered by arbitrarily oriented parallel virtual planes. .Iaddend. .Iadd.19. The method of claim 17 wherein the projected representation is a 2-dimensional representation of a portion of the specimen bordered by arbitrarily oriented nonparallel virtual planes. .Iaddend. .Iadd.20. An apparatus for microphotometering a 3-dimensional specimen, the specimen defining a plurality of layers, each layer defining a plurality of part elements, the apparatus comprising:
means for detecting light from a focal plane;
means for generating a cursor of light in the focal plane;
means for positioning at least one of (1) the focal plane and (2) the specimen such that a desired one of the layers lies in the focal plane;
means for positioning at least one of (1) the cursor and (2) the specimen to illuminate by means of the cursor a selected part element;
means fore preventing unwanted light from part elements adjacent the selected part element from being detected by the means for detecting light;
means for producing signals indicative of predetermined characteristics of the detected light;
means for storing representations of the signals; and
means for analyzing the representations of the signals to produce measurements of the specimen representative of at least one 3-dimensional
characteristic of at least a portion of the specimen. .Iaddend. .Iadd.21. An apparatus for microphotometering a 3-dimensional specimen, the specimen defining a plurality of layers, each layer defining a plurality of part elements, the apparatus comprising:
means for detecting light from a focal plane;
means for generating a cursor of light in the focal plane;
means for positioning at least one of (1) the focal plane and (2) the specimen such that a desired one of the layers lies in the focal plane;
means for positioning at least one of (1) the cursor and (2) the specimen to illuminate by means of the cursor a selected part element;
means for preventing unwanted light from part elements adjacent the selected part element from being detected by the means for detecting light;
means for producing signals indicative of predetermined characteristics of the detected light;
means for storing representations of the signals; and
means for analyzing the representations of the signals to produce a projected representation from a desired angle of at least a portion of the specimen. .Iaddend.
US07288287 1984-03-15 1988-12-21 Method and apparatus for microphotometering microscope specimens Expired - Lifetime USRE34214E (en)

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US5479252A (en) * 1993-06-17 1995-12-26 Ultrapointe Corporation Laser imaging system for inspection and analysis of sub-micron particles
USH1530H (en) * 1993-06-17 1996-05-07 Ultrapointe Corporation Surface extraction from a three-dimensional data set
US5621532A (en) * 1994-12-08 1997-04-15 Nikon Corporation Laser scanning microscope utilizing detection of a far-field diffraction pattern with 2-dimensional detection
US5713364A (en) * 1995-08-01 1998-02-03 Medispectra, Inc. Spectral volume microprobe analysis of materials
EP0533330B1 (en) * 1991-09-17 1998-04-22 Hitachi, Ltd. A scanning microscope and a method of operating such a scanning microscope
US5813987A (en) * 1995-08-01 1998-09-29 Medispectra, Inc. Spectral volume microprobe for analysis of materials
US5880880A (en) * 1995-01-13 1999-03-09 The General Hospital Corp. Three-dimensional scanning confocal laser microscope
US5923430A (en) * 1993-06-17 1999-07-13 Ultrapointe Corporation Method for characterizing defects on semiconductor wafers
US6148114A (en) 1996-11-27 2000-11-14 Ultrapointe Corporation Ring dilation and erosion techniques for digital image processing
US6369379B1 (en) 1994-07-28 2002-04-09 General Nanotechnology Llc Scanning probe microscope assembly and method for making confocal, spectrophotometric, near-field, and scanning probe measurements and associated images
US20020049544A1 (en) * 2000-06-23 2002-04-25 Cytokinetics, Inc. Image analysis for phenotyping sets of mutant cells
US6385484B2 (en) 1998-12-23 2002-05-07 Medispectra, Inc. Spectroscopic system employing a plurality of data types
US20020101655A1 (en) * 1999-02-17 2002-08-01 Greenwald Roger J. Tissue specimen holder
US20020127735A1 (en) * 1999-12-15 2002-09-12 Howard Kaufman Methods of monitoring effects of chemical agents on a sample
US20020135755A1 (en) * 1994-07-28 2002-09-26 Kley Victor B. Scanning probe microscope assembly
US20020141631A1 (en) * 2001-02-20 2002-10-03 Cytokinetics, Inc. Image analysis of the golgi complex
US20020154399A1 (en) * 1999-02-17 2002-10-24 Eastman Jay M. Cassette for facilitating optical sectioning of a retained tissue specimen
US20020177777A1 (en) * 1998-12-23 2002-11-28 Medispectra, Inc. Optical methods and systems for rapid screening of the cervix
US6599694B2 (en) 2000-12-18 2003-07-29 Cytokinetics, Inc. Method of characterizing potential therapeutics by determining cell-cell interactions
US20030144585A1 (en) * 1999-12-15 2003-07-31 Howard Kaufman Image processing using measures of similarity
US6615141B1 (en) 1999-05-14 2003-09-02 Cytokinetics, Inc. Database system for predictive cellular bioinformatics
US6651008B1 (en) 1999-05-14 2003-11-18 Cytokinetics, Inc. Database system including computer code for predictive cellular bioinformatics
US20040007674A1 (en) * 2002-07-09 2004-01-15 Schomacker Kevin T. Method and apparatus for identifying spectral artifacts
US6684092B2 (en) 1997-02-24 2004-01-27 Lucid, Inc. System for facilitating pathological examination of a lesion in tissue
US6752008B1 (en) 2001-03-08 2004-06-22 General Nanotechnology Llc Method and apparatus for scanning in scanning probe microscopy and presenting results
US20040118192A1 (en) * 2002-09-09 2004-06-24 General Nanotechnology Llc Fluid delivery for scanning probe microscopy
US6768918B2 (en) 2002-07-10 2004-07-27 Medispectra, Inc. Fluorescent fiberoptic probe for tissue health discrimination and method of use thereof
US6787768B1 (en) 2001-03-08 2004-09-07 General Nanotechnology Llc Method and apparatus for tool and tip design for nanomachining and measurement
US6802646B1 (en) 2001-04-30 2004-10-12 General Nanotechnology Llc Low-friction moving interfaces in micromachines and nanomachines
US20040206882A1 (en) * 2003-04-18 2004-10-21 Medispectra, Inc. Methods and apparatus for evaluating image focus
US20040208385A1 (en) * 2003-04-18 2004-10-21 Medispectra, Inc. Methods and apparatus for visually enhancing images
US20040208390A1 (en) * 2003-04-18 2004-10-21 Medispectra, Inc. Methods and apparatus for processing image data for use in tissue characterization
US20040209237A1 (en) * 2003-04-18 2004-10-21 Medispectra, Inc. Methods and apparatus for characterization of tissue samples
US6813937B2 (en) 2001-11-28 2004-11-09 General Nanotechnology Llc Method and apparatus for micromachines, microstructures, nanomachines and nanostructures
US6826422B1 (en) 1997-01-13 2004-11-30 Medispectra, Inc. Spectral volume microprobe arrays
US6831994B2 (en) 1997-05-23 2004-12-14 Lynx Therapeutics, Inc. System and apparatus for sequential processing of analytes
US6839661B2 (en) 2000-12-15 2005-01-04 Medispectra, Inc. System for normalizing spectra
US6847490B1 (en) 1997-01-13 2005-01-25 Medispectra, Inc. Optical probe accessory device for use in vivo diagnostic procedures
US6865927B1 (en) 2001-01-30 2005-03-15 General Nanotechnology Llc Sharpness testing of micro-objects such as miniature diamond tool tips
US20050056783A1 (en) * 1999-07-01 2005-03-17 General Nanotechnology, Llc Object inspection and/or modification system and method
US6876760B1 (en) 2000-12-04 2005-04-05 Cytokinetics, Inc. Classifying cells based on information contained in cell images
US6880388B1 (en) 2001-03-08 2005-04-19 General Nanotechnology Llc Active cantilever for nanomachining and metrology
US20050137806A1 (en) * 2003-07-18 2005-06-23 Cytokinetics, Inc. A Delaware Corporation Characterizing biological stimuli by response curves
US6933154B2 (en) 2002-07-09 2005-08-23 Medispectra, Inc. Optimal windows for obtaining optical data for characterization of tissue samples
US20050190684A1 (en) * 1995-07-24 2005-09-01 General Nanotechnology Llc Nanometer scale data storage device and associated positioning system
US6956961B2 (en) 2001-02-20 2005-10-18 Cytokinetics, Inc. Extracting shape information contained in cell images
US20050273271A1 (en) * 2004-04-05 2005-12-08 Aibing Rao Method of characterizing cell shape
US20050272073A1 (en) * 2000-12-04 2005-12-08 Cytokinetics, Inc., A Delaware Corporation Ploidy classification method
US20060014135A1 (en) * 2004-07-15 2006-01-19 Cytokinetics, Inc. Assay for distinguishing live and dead cells
US7016787B2 (en) 2001-02-20 2006-03-21 Cytokinetics, Inc. Characterizing biological stimuli by response curves
US7045780B2 (en) 1994-07-28 2006-05-16 General Nanotechnology, Llc Scanning probe microscopy inspection and modification system
US7053369B1 (en) 2001-10-19 2006-05-30 Rave Llc Scan data collection for better overall data accuracy
US7103401B2 (en) 2002-07-10 2006-09-05 Medispectra, Inc. Colonic polyp discrimination by tissue fluorescence and fiberoptic probe
US20060228695A1 (en) * 2003-07-18 2006-10-12 Cytokinetics, Inc. Predicting hepatotoxicity using cell based assays
US20060239329A1 (en) * 2005-03-14 2006-10-26 Kabushiki Kaisha Bio Echo Net Ear-type clinical thermometer
US7136518B2 (en) 2003-04-18 2006-11-14 Medispectra, Inc. Methods and apparatus for displaying diagnostic data
US20070031818A1 (en) * 2004-07-15 2007-02-08 Cytokinetics, Inc., A Delaware Corporation Assay for distinguishing live and dead cells
US7187810B2 (en) 1999-12-15 2007-03-06 Medispectra, Inc. Methods and systems for correcting image misalignment
US7194118B1 (en) * 2000-11-10 2007-03-20 Lucid, Inc. System for optically sectioning and mapping surgically excised tissue
US7196328B1 (en) 2001-03-08 2007-03-27 General Nanotechnology Llc Nanomachining method and apparatus
US7235353B2 (en) 2003-07-18 2007-06-26 Cytokinetics, Inc. Predicting hepatotoxicity using cell based assays
US7253407B1 (en) 2001-03-08 2007-08-07 General Nanotechnology Llc Active cantilever for nanomachining and metrology
US20070206275A1 (en) * 2006-02-17 2007-09-06 Paul Hemmer System for macroscopic and confocal imaging of tissue
US7282723B2 (en) 2002-07-09 2007-10-16 Medispectra, Inc. Methods and apparatus for processing spectral data for use in tissue characterization
US7309867B2 (en) 2003-04-18 2007-12-18 Medispectra, Inc. Methods and apparatus for characterization of tissue samples
EP1873232A1 (en) 2006-06-29 2008-01-02 Fujitsu Limited Microinjection apparatus and automatic focal point adjustment method
US7459696B2 (en) 2003-04-18 2008-12-02 Schomacker Kevin T Methods and apparatus for calibrating spectral data
US20090259446A1 (en) * 2008-04-10 2009-10-15 Schlumberger Technology Corporation Method to generate numerical pseudocores using borehole images, digital rock samples, and multi-point statistics
US20110004447A1 (en) * 2009-07-01 2011-01-06 Schlumberger Technology Corporation Method to build 3D digital models of porous media using transmitted laser scanning confocal mircoscopy and multi-point statistics
US20110004448A1 (en) * 2009-07-01 2011-01-06 Schlumberger Technology Corporation Method to quantify discrete pore shapes, volumes, and surface areas using confocal profilometry
USRE43097E1 (en) 1994-10-13 2012-01-10 Illumina, Inc. Massively parallel signature sequencing by ligation of encoded adaptors
US8369591B2 (en) 2003-04-11 2013-02-05 Carl Zeiss Microimaging Gmbh Silhouette image acquisition
US9229210B2 (en) 2012-02-26 2016-01-05 Caliber Imaging And Diagnostics, Inc. Tissue specimen stage for an optical sectioning microscope
US9581723B2 (en) 2008-04-10 2017-02-28 Schlumberger Technology Corporation Method for characterizing a geological formation traversed by a borehole

Families Citing this family (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3614359C2 (en) * 1985-07-26 1997-04-24 Zeiss Carl Jena Gmbh A device for analysis and graphic representation of the resulting laser light at a point-wise excitation of a preparation time intensity curve of the fluorescent radiation
GB8531011D0 (en) * 1985-12-17 1986-01-29 Medical Res Council Confocal scanning microscope
US4845556A (en) * 1987-10-30 1989-07-04 General Electric Company Video spot detector
US4997242A (en) * 1988-03-07 1991-03-05 Medical Research Council Achromatic scanning system
US5144477A (en) * 1988-04-11 1992-09-01 Medical Research Council Method of operating a scanning confocal imaging system
US5032720A (en) * 1988-04-21 1991-07-16 White John G Confocal imaging system
US5022757A (en) * 1989-01-23 1991-06-11 Modell Mark D Heterodyne system and method for sensing a target substance
US5026159A (en) * 1989-05-19 1991-06-25 Acrogen, Inc. Area-modulated luminescence (AML)
US5190857A (en) * 1989-05-19 1993-03-02 Acrogen, Inc. Optical method for measuring an analyte using area-modulated luminescence
US5034613A (en) * 1989-11-14 1991-07-23 Cornell Research Foundation, Inc. Two-photon laser microscopy
JPH06100545B2 (en) * 1991-01-31 1994-12-12 株式会社島津製作所 Fluorescent image densitometer by the flying spot method
US5225923A (en) * 1992-07-09 1993-07-06 General Scanning, Inc. Scanning microscope employing improved scanning mechanism
DE4416558C2 (en) * 1994-02-01 1997-09-04 Hell Stefan A method of optically measuring a sample point of a sample and apparatus for carrying out the method
DE19520606B4 (en) * 1995-06-06 2004-04-08 Roche Diagnostics Gmbh An apparatus for optical examination of surfaces
DE69635521D1 (en) 1995-09-19 2006-01-05 Cornell Res Foundation Inc Multiphoton laser microscopy
US6133986A (en) * 1996-02-28 2000-10-17 Johnson; Kenneth C. Microlens scanner for microlithography and wide-field confocal microscopy
US5837475A (en) * 1997-01-30 1998-11-17 Hewlett-Packard Co. Apparatus and method for scanning a chemical array
US6201639B1 (en) 1998-03-20 2001-03-13 James W. Overbeck Wide field of view and high speed scanning microscopy
US6185030B1 (en) 1998-03-20 2001-02-06 James W. Overbeck Wide field of view and high speed scanning microscopy
US6166373A (en) * 1998-07-21 2000-12-26 The Institute For Technology Development Focal plane scanner with reciprocating spatial window
US6438261B1 (en) * 1998-09-03 2002-08-20 Green Vision Systems Ltd. Method of in-situ focus-fusion multi-layer spectral imaging and analysis of particulate samples
EP1131673A2 (en) 1998-11-25 2001-09-12 Phormax Corporation Single-head phosphor screen scanning systems
DE19908883A1 (en) 1999-03-02 2000-09-07 Rainer Heintzmann Method for increasing the resolution of optical imaging
US6548796B1 (en) 1999-06-23 2003-04-15 Regents Of The University Of Minnesota Confocal macroscope
GB2385481B (en) 2002-02-13 2004-01-07 Fairfield Imaging Ltd Microscopy imaging system and method
DE10231543B3 (en) * 2002-07-11 2004-02-26 Universität Siegen Confocal 3D scanning absorption
US20050012057A1 (en) * 2003-05-08 2005-01-20 Alara, Inc. Method and apparatus for radiation image erasure
JP2007166981A (en) * 2005-12-22 2007-07-05 Fujitsu Ltd Injector and method
DE102009029831A1 (en) 2009-06-17 2011-01-13 W.O.M. World Of Medicine Ag Apparatus and method for multi-photon fluorescence microscopy for obtaining information from biological tissue

Citations (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2969708A (en) * 1957-04-03 1961-01-31 American Optical Corp Means for analyzing microscopic particles and the like
US3013467A (en) * 1957-11-07 1961-12-19 Minsky Marvin Microscopy apparatus
US3049047A (en) * 1957-04-03 1962-08-14 American Optical Corp Method for analyzing microscopic particles and the like
US3719776A (en) * 1969-08-11 1973-03-06 Hitachi Ltd Apparatus for photographing an image of a specimen
US3764512A (en) * 1972-05-02 1973-10-09 Singer Co Laser scanning electrophoresis instrument and system
US3782823A (en) * 1972-03-23 1974-01-01 American Optical Corp Laser microprobe
US3790281A (en) * 1973-02-26 1974-02-05 Zenith Radio Corp Combined system for acoustical-optical microscopy
DE2360197A1 (en) * 1973-12-03 1975-06-05 Ibm Deutschland Method for increasing the depth of field and / or the angular resolution of optical microscopes
US3926500A (en) * 1974-12-02 1975-12-16 Ibm Method of increasing the depth of focus and or the resolution of light microscopes by illuminating and imaging through a diaphragm with pinhole apertures
US3947628A (en) * 1974-08-21 1976-03-30 Imant Karlovich Alien Device for selective search of objects using images thereof
US3980818A (en) * 1968-08-21 1976-09-14 Sydnor-Barent, Inc. Recorder and reproducer system
US4045772A (en) * 1974-04-29 1977-08-30 Geometric Data Corporation Automatic focusing system
US4068381A (en) * 1976-10-29 1978-01-17 The United States Of America As Represented By The Secretary Of Commerce Scanning electron microscope micrometer scale and method for fabricating same
DE2655525A1 (en) * 1976-12-08 1978-06-15 Leitz Ernst Gmbh A process for the expansion of the schaerfentiefebereiches over the given by the konvnetionelle illustration limit and means for carrying out this method
US4125828A (en) * 1972-08-04 1978-11-14 Med-El Inc. Method and apparatus for automated classification and analysis of cells
US4160263A (en) * 1978-05-15 1979-07-03 George R. Cogar Dual or multiple objective video microscope for superimposing spaced images
US4194217A (en) * 1978-03-31 1980-03-18 Bosch Francois J G Van Den Method and apparatus for in-vivo spectroscopic analysis
US4207554A (en) * 1972-08-04 1980-06-10 Med-El Inc. Method and apparatus for automated classification and analysis of cells
US4211924A (en) * 1976-09-03 1980-07-08 Siemens Aktiengesellschaft Transmission-type scanning charged-particle beam microscope
US4218112A (en) * 1978-07-03 1980-08-19 C. Reichert Optische Werke, Ag Photometer microscope for microphotometer scanning of fine specimen structures
US4223354A (en) * 1978-08-30 1980-09-16 General Electric Company Phase corrected raster scanned light modulator and a variable frequency oscillator for effecting phase correction
US4236179A (en) * 1979-06-29 1980-11-25 International Business Machines Corporation Versatile microsecond multiple framing camera
US4255971A (en) * 1978-11-01 1981-03-17 Allan Rosencwaig Thermoacoustic microscopy
US4284897A (en) * 1977-04-30 1981-08-18 Olympus Optical Company Ltd. Fluorescence determining microscope utilizing laser light
US4311358A (en) * 1978-11-01 1982-01-19 De Forenede Bryggerier A/S Illumination device for fluorescence microscopes
US4314763A (en) * 1979-01-04 1982-02-09 Rca Corporation Defect detection system
US4348263A (en) * 1980-09-12 1982-09-07 Western Electric Company, Inc. Surface melting of a substrate prior to plating
US4350892A (en) * 1980-07-31 1982-09-21 Research Corporation X'-, Y'-, Z'- axis multidimensional slit-scan flow system
US4354114A (en) * 1979-10-09 1982-10-12 Karnaukhov Valery N Apparatus for investigation of fluorescence characteristics of microscopic objects
US4362943A (en) * 1980-09-08 1982-12-07 Bell Telephone Laboratories, Incorporated Method of measuring the refractive index profile and the core diameter of optical fibers and preforms
US4366380A (en) * 1979-10-11 1982-12-28 George Mirkin Method and apparatus for structural analysis
US4379135A (en) * 1978-03-10 1983-04-05 Lion Corporation Method for enumeration of oral gram-negative bacteria
US4379231A (en) * 1979-03-14 1983-04-05 Hitachi, Ltd. Electron microscope
US4381963A (en) * 1980-07-30 1983-05-03 The University Of Rochester Micro fabrication molding process
DE3243890A1 (en) * 1981-11-26 1983-06-09 Secr Defence Brit imaging system
US4405237A (en) * 1981-02-04 1983-09-20 The United States Of America As Represented By The Secretary Of The Navy Coherent anti-Stokes Raman device
US4406015A (en) * 1980-09-22 1983-09-20 Kabushiki Kaisha Daini Seikosha Fluorescent X-ray film thickness gauge
US4407008A (en) * 1980-10-08 1983-09-27 Carl Zeiss-Stiftung Method and apparatus for light-induced scanning-microscope display of specimen parameters and of their distribution
US4406525A (en) * 1979-11-19 1983-09-27 Asahi Kogaku Kogyo Kabushiki Kaisha Light beam scanning device
EP0112401A1 (en) * 1982-12-27 1984-07-04 International Business Machines Corporation Optical near-field scanning microscope
US4485409A (en) * 1982-03-29 1984-11-27 Measuronics Corporation Data acquisition system for large format video display
GB2184321A (en) * 1985-12-17 1987-06-17 Medical Res Council Confocal scanning microscope

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS58169473A (en) * 1982-03-31 1983-10-05 Matsushita Electric Works Ltd Balance function exerciser

Patent Citations (43)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3049047A (en) * 1957-04-03 1962-08-14 American Optical Corp Method for analyzing microscopic particles and the like
US2969708A (en) * 1957-04-03 1961-01-31 American Optical Corp Means for analyzing microscopic particles and the like
US3013467A (en) * 1957-11-07 1961-12-19 Minsky Marvin Microscopy apparatus
US3980818A (en) * 1968-08-21 1976-09-14 Sydnor-Barent, Inc. Recorder and reproducer system
US3719776A (en) * 1969-08-11 1973-03-06 Hitachi Ltd Apparatus for photographing an image of a specimen
US3782823A (en) * 1972-03-23 1974-01-01 American Optical Corp Laser microprobe
US3764512A (en) * 1972-05-02 1973-10-09 Singer Co Laser scanning electrophoresis instrument and system
US4125828A (en) * 1972-08-04 1978-11-14 Med-El Inc. Method and apparatus for automated classification and analysis of cells
US4207554A (en) * 1972-08-04 1980-06-10 Med-El Inc. Method and apparatus for automated classification and analysis of cells
US3790281A (en) * 1973-02-26 1974-02-05 Zenith Radio Corp Combined system for acoustical-optical microscopy
DE2360197A1 (en) * 1973-12-03 1975-06-05 Ibm Deutschland Method for increasing the depth of field and / or the angular resolution of optical microscopes
US4045772A (en) * 1974-04-29 1977-08-30 Geometric Data Corporation Automatic focusing system
US3947628A (en) * 1974-08-21 1976-03-30 Imant Karlovich Alien Device for selective search of objects using images thereof
US3926500A (en) * 1974-12-02 1975-12-16 Ibm Method of increasing the depth of focus and or the resolution of light microscopes by illuminating and imaging through a diaphragm with pinhole apertures
US4211924A (en) * 1976-09-03 1980-07-08 Siemens Aktiengesellschaft Transmission-type scanning charged-particle beam microscope
US4068381A (en) * 1976-10-29 1978-01-17 The United States Of America As Represented By The Secretary Of Commerce Scanning electron microscope micrometer scale and method for fabricating same
DE2655525A1 (en) * 1976-12-08 1978-06-15 Leitz Ernst Gmbh A process for the expansion of the schaerfentiefebereiches over the given by the konvnetionelle illustration limit and means for carrying out this method
US4141032A (en) * 1976-12-08 1979-02-20 Ernst Leitz Wetzlar Gmbh Method of and apparatus for the expansion of the range of the depth of focus beyond the limit given by conventional images
US4284897A (en) * 1977-04-30 1981-08-18 Olympus Optical Company Ltd. Fluorescence determining microscope utilizing laser light
US4379135A (en) * 1978-03-10 1983-04-05 Lion Corporation Method for enumeration of oral gram-negative bacteria
US4194217A (en) * 1978-03-31 1980-03-18 Bosch Francois J G Van Den Method and apparatus for in-vivo spectroscopic analysis
US4160263A (en) * 1978-05-15 1979-07-03 George R. Cogar Dual or multiple objective video microscope for superimposing spaced images
US4218112A (en) * 1978-07-03 1980-08-19 C. Reichert Optische Werke, Ag Photometer microscope for microphotometer scanning of fine specimen structures
US4223354A (en) * 1978-08-30 1980-09-16 General Electric Company Phase corrected raster scanned light modulator and a variable frequency oscillator for effecting phase correction
US4255971A (en) * 1978-11-01 1981-03-17 Allan Rosencwaig Thermoacoustic microscopy
US4311358A (en) * 1978-11-01 1982-01-19 De Forenede Bryggerier A/S Illumination device for fluorescence microscopes
US4314763A (en) * 1979-01-04 1982-02-09 Rca Corporation Defect detection system
US4379231A (en) * 1979-03-14 1983-04-05 Hitachi, Ltd. Electron microscope
US4236179A (en) * 1979-06-29 1980-11-25 International Business Machines Corporation Versatile microsecond multiple framing camera
US4354114A (en) * 1979-10-09 1982-10-12 Karnaukhov Valery N Apparatus for investigation of fluorescence characteristics of microscopic objects
US4366380A (en) * 1979-10-11 1982-12-28 George Mirkin Method and apparatus for structural analysis
US4406525A (en) * 1979-11-19 1983-09-27 Asahi Kogaku Kogyo Kabushiki Kaisha Light beam scanning device
US4381963A (en) * 1980-07-30 1983-05-03 The University Of Rochester Micro fabrication molding process
US4350892A (en) * 1980-07-31 1982-09-21 Research Corporation X'-, Y'-, Z'- axis multidimensional slit-scan flow system
US4362943A (en) * 1980-09-08 1982-12-07 Bell Telephone Laboratories, Incorporated Method of measuring the refractive index profile and the core diameter of optical fibers and preforms
US4348263A (en) * 1980-09-12 1982-09-07 Western Electric Company, Inc. Surface melting of a substrate prior to plating
US4406015A (en) * 1980-09-22 1983-09-20 Kabushiki Kaisha Daini Seikosha Fluorescent X-ray film thickness gauge
US4407008A (en) * 1980-10-08 1983-09-27 Carl Zeiss-Stiftung Method and apparatus for light-induced scanning-microscope display of specimen parameters and of their distribution
US4405237A (en) * 1981-02-04 1983-09-20 The United States Of America As Represented By The Secretary Of The Navy Coherent anti-Stokes Raman device
DE3243890A1 (en) * 1981-11-26 1983-06-09 Secr Defence Brit imaging system
US4485409A (en) * 1982-03-29 1984-11-27 Measuronics Corporation Data acquisition system for large format video display
EP0112401A1 (en) * 1982-12-27 1984-07-04 International Business Machines Corporation Optical near-field scanning microscope
GB2184321A (en) * 1985-12-17 1987-06-17 Medical Res Council Confocal scanning microscope

Non-Patent Citations (43)

* Cited by examiner, † Cited by third party
Title
"A Laser Flying Spot Scanner for Use in Automated Fluorescence Antibody Instrumentation", A. F. Slomba, D. E. Wasserman, G. I. Kaufman, J. F. Nester, Journal of the Association for the Advancement of Medical Instrumentation, vol. 6, No. 3, May-Jun., 1972, pp. 230-234.
"Automatic Moving Part Measuring Equipment", H. M. Nier, IBM Technical Disclosure Bulletin, vol. 22, No. 7, Dec., 1979, pp. 2856-2857.
"Depth of Field in the Scanning Microscope", C. J. R. Sheppard, T. Wilson, Optics Letters, vol. 3, No. 3, Sep., 1978, pp. 115-117.
"Digital Image Processing of Confocal Images", I. J. Cox, C. J. R. Sheppard, Image and Vision Computing, 1983, Butterworth & Co., Ltd. (Publishers), pp. 52-56.
"Dynamic Focusing in the Confocal Scanning Microscope", T. Wilson D. K. Hamilton, Journal of Microscopy, vol. 128, pt. 2, Nov., 1982, pp. 139-143.
"Electronic Image Processing of Scanning Optical Microscope Images", I. J. Cox, presented at International Conference on Electronic Image Processing, Jul. 26-28, 1982.
"Experimental Observations of the Depth-Discrimination Properties of Scanning Microscopes", D. K. Hamilton, T. Wilson, C. J. R. Sheppard, Optics Letters, Dec., 1981, vol. 6, No. 12, pp. 625-626.
"Image-analyzing Microscopes", Phillip G. Stein, Analytical Chemistry, vol. 42, No. 13, Nov., 1970, pp. 103A-106A.
"Laser Scanning Microscopy", W. Jerry Alford, Richard D. Vanderneut, Vincent J. Zaleckas, Proceedings of the IEEE, vol. 70, No. 6, Jun., 1982, pp. 641-651.
"Morphoquant-An Automatic Microimage Analyzer of VEB Carl Zeiss Jena", Shura Agadshanyan, Peter Dopel, Peter Gretscher, Werner Witsack, JR 6, 1977, pp. 270-276.
"Optical Microscopy with Extended Depth of Field", C. J. R. Sheppard, D. K. Hamilton, I. J. Cox, Proc. R. Soc. Lond. A, vol. 387, pp. 171-186.
"PHOIBOS, A Microscope Scanner Designed for Micro-fluorometric Applications, Using Laser Induced Fluoroscence", N. Aslund, K. Carlsson, A. Liljeborg, L. Majlof, Physics IV, Royal Institute of Technology, S-100 44 Stockholm 70, 1983, pp. 338-343.
"Scanning Laser Microscope for Biological Investigations", P. Davidovits, M. D. Egger, Applied Optics, vol. 10, No. 7, Jul., 1971, pp. 1615-1619.
"Scanning Laser Microscope", Paul Davidovits, M. David Egger, Nature, vol. 223, Aug. 1969, p. 831.
"Scanning Optical Microscope Incorporating a Digital Framestore and Microcomputer", I. J. Cox, C. J. R. Sheppard, 2219 Applied Optics vol. 22, No. 10, May, 1983, New York, U.S.A., pp. 1474-1478.
"Tandem Scanning Reflected Light Microscopy of Internal Features in Whole Bone and Tooth Samples" A. Boyde, M. Petran, M. Hadravsky, Journal of Microscopy, vol. 132, part 1, Oct., 1983, pp. 1-7.
"Tandem-scanning Reflected-light Microscope", Mojmir Petran, Milan Hadravsky, M. David Egger, Robert Galambos, Journal of the Optical Society of America, vol. 58, No. 5, May, 1968, pp. 661-664.
"Three-dimensional Architecture of a Polytene Nucleus", David A. Agard, John W. Sedat, Nature, vol. 302, Apr. 21, 1983, pp. 676-681.
A Laser Flying Spot Scanner for Use in Automated Fluorescence Antibody Instrumentation , A. F. Slomba, D. E. Wasserman, G. I. Kaufman, J. F. Nester, Journal of the Association for the Advancement of Medical Instrumentation, vol. 6, No. 3, May Jun., 1972, pp. 230 234. *
Automatic Moving Part Measuring Equipment , H. M. Nier, IBM Technical Disclosure Bulletin, vol. 22, No. 7, Dec., 1979, pp. 2856 2857. *
D. K. Hamilton et al., "Three-Dimensional Surface Measurement Using the Confocal Scanning Microscope", Applied Physics B27, pp. 211-213 (1982).
D. K. Hamilton et al., Three Dimensional Surface Measurement Using the Confocal Scanning Microscope , Applied Physics B27, pp. 211 213 (1982). *
Depth of Field in the Scanning Microscope , C. J. R. Sheppard, T. Wilson, Optics Letters, vol. 3, No. 3, Sep., 1978, pp. 115 117. *
Digital Image Processing of Confocal Images , I. J. Cox, C. J. R. Sheppard, Image and Vision Computing, 1983, Butterworth & Co., Ltd. (Publishers), pp. 52 56. *
Digital Image Processing, Kenneth R. Castleman, 1979 Prentice Hall, Inc. *
Digital Image Processing, Kenneth R. Castleman, 1979 Prentice-Hall, Inc.
Dynamic Focusing in the Confocal Scanning Microscope , T. Wilson D. K. Hamilton, Journal of Microscopy, vol. 128, pt. 2, Nov., 1982, pp. 139 143. *
Electronic Image Processing of Scanning Optical Microscope Images , I. J. Cox, presented at International Conference on Electronic Image Processing, Jul. 26 28, 1982. *
Experimental Observations of the Depth Discrimination Properties of Scanning Microscopes , D. K. Hamilton, T. Wilson, C. J. R. Sheppard, Optics Letters, Dec., 1981, vol. 6, No. 12, pp. 625 626. *
G. J. Brakenhoff, "Imaging modes in confocal scanning light microscopy (CSLM)", Journal of Microscopy, vol. 117, pt. 2, Nov. 1979, pp. 233-242.
G. J. Brakenhoff, Imaging modes in confocal scanning light microscopy (CSLM) , Journal of Microscopy, vol. 117, pt. 2, Nov. 1979, pp. 233 242. *
Image analyzing Microscopes , Phillip G. Stein, Analytical Chemistry, vol. 42, No. 13, Nov., 1970, pp. 103A 106A. *
Laser Scanning Microscopy , W. Jerry Alford, Richard D. Vanderneut, Vincent J. Zaleckas, Proceedings of the IEEE, vol. 70, No. 6, Jun., 1982, pp. 641 651. *
Morphoquant An Automatic Microimage Analyzer of VEB Carl Zeiss Jena , Shura Agadshanyan, Peter Dopel, Peter Gretscher, Werner Witsack, JR 6, 1977, pp. 270 276. *
Optical Microscopy with Extended Depth of Field , C. J. R. Sheppard, D. K. Hamilton, I. J. Cox, Proc. R. Soc. Lond. A, vol. 387, pp. 171 186. *
PHOIBOS, A Microscope Scanner Designed for Micro fluorometric Applications, Using Laser Induced Fluoroscence , N. Aslund, K. Carlsson, A. Liljeborg, L. Majlof, Physics IV, Royal Institute of Technology, S 100 44 Stockholm 70, 1983, pp. 338 343. *
Scanning Laser Microscope , Paul Davidovits, M. David Egger, Nature, vol. 223, Aug. 1969, p. 831. *
Scanning Laser Microscope for Biological Investigations , P. Davidovits, M. D. Egger, Applied Optics, vol. 10, No. 7, Jul., 1971, pp. 1615 1619. *
Scanning Optical Microscope Incorporating a Digital Framestore and Microcomputer , I. J. Cox, C. J. R. Sheppard, 2219 Applied Optics vol. 22, No. 10, May, 1983, New York, U.S.A., pp. 1474 1478. *
Tandem scanning Reflected light Microscope , Mojmir Petran, Milan Hadravsky, M. David Egger, Robert Galambos, Journal of the Optical Society of America, vol. 58, No. 5, May, 1968, pp. 661 664. *
Tandem Scanning Reflected Light Microscopy of Internal Features in Whole Bone and Tooth Samples A. Boyde, M. Petran, M. Hadravsky, Journal of Microscopy, vol. 132, part 1, Oct., 1983, pp. 1 7. *
The Engineering Index Annual, 1983, pp. 3434 and 4491. *
Three dimensional Architecture of a Polytene Nucleus , David A. Agard, John W. Sedat, Nature, vol. 302, Apr. 21, 1983, pp. 676 681. *

Cited By (144)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0533330B1 (en) * 1991-09-17 1998-04-22 Hitachi, Ltd. A scanning microscope and a method of operating such a scanning microscope
US20070104357A1 (en) * 1993-06-17 2007-05-10 Kla-Tencor Corporation Method for Characterizing Defects on Semiconductor Wafers
USH1530H (en) * 1993-06-17 1996-05-07 Ultrapointe Corporation Surface extraction from a three-dimensional data set
US6661515B2 (en) 1993-06-17 2003-12-09 Kla-Tencor Corporation Method for characterizing defects on semiconductor wafers
US6288782B1 (en) 1993-06-17 2001-09-11 Ultrapointe Corporation Method for characterizing defects on semiconductor wafers
US20030203520A1 (en) * 1993-06-17 2003-10-30 Worster Bruce W. Method for characterizing defects on semiconductor wafers
US5479252A (en) * 1993-06-17 1995-12-26 Ultrapointe Corporation Laser imaging system for inspection and analysis of sub-micron particles
US5923430A (en) * 1993-06-17 1999-07-13 Ultrapointe Corporation Method for characterizing defects on semiconductor wafers
US20020135755A1 (en) * 1994-07-28 2002-09-26 Kley Victor B. Scanning probe microscope assembly
US20060237639A1 (en) * 1994-07-28 2006-10-26 General Nanotechnology Llc Scanning probe microscope assembly and method for making spectrophotometric, near-filed, and scanning probe measurements
US6369379B1 (en) 1994-07-28 2002-04-09 General Nanotechnology Llc Scanning probe microscope assembly and method for making confocal, spectrophotometric, near-field, and scanning probe measurements and associated images
US7615738B2 (en) 1994-07-28 2009-11-10 General Nanotechnology, Llc Scanning probe microscope assembly and method for making spectrophotometric, near-field, and scanning probe measurements
US7045780B2 (en) 1994-07-28 2006-05-16 General Nanotechnology, Llc Scanning probe microscopy inspection and modification system
US6396054B1 (en) 1994-07-28 2002-05-28 General Nanotechnology Llc Scanning probe microscope assembly and method for making confocal, spectrophotometric, near-field, and scanning probe measurements and associated images
US7091476B2 (en) 1994-07-28 2006-08-15 General Nanotechnology Llc Scanning probe microscope assembly
US20070022804A1 (en) * 1994-07-28 2007-02-01 General Nanotechnology Llc Scanning probe microscopy inspection and modification system
US7485856B2 (en) 1994-07-28 2009-02-03 General Nanotechnology Llp Scanning probe microscopy inspection and modification system
US6515277B1 (en) 1994-07-28 2003-02-04 General Nanotechnology L.L.C. Scanning probe microscope assembly and method for making confocal, spectrophotometric, near-field, and scanning probe measurements and associated images
USRE43097E1 (en) 1994-10-13 2012-01-10 Illumina, Inc. Massively parallel signature sequencing by ligation of encoded adaptors
US5621532A (en) * 1994-12-08 1997-04-15 Nikon Corporation Laser scanning microscope utilizing detection of a far-field diffraction pattern with 2-dimensional detection
US5880880A (en) * 1995-01-13 1999-03-09 The General Hospital Corp. Three-dimensional scanning confocal laser microscope
US7535817B2 (en) 1995-07-24 2009-05-19 General Nanotechnology, L.L.C. Nanometer scale data storage device and associated positioning system
US20050190684A1 (en) * 1995-07-24 2005-09-01 General Nanotechnology Llc Nanometer scale data storage device and associated positioning system
US7042828B2 (en) 1995-07-24 2006-05-09 General Nanotechnology Llc Nanometer scale data storage device and associated positioning system
US20060239129A1 (en) * 1995-07-24 2006-10-26 General Nanotechnology Llc Nanometer scale data storage device and associated positioning system
US5713364A (en) * 1995-08-01 1998-02-03 Medispectra, Inc. Spectral volume microprobe analysis of materials
US5813987A (en) * 1995-08-01 1998-09-29 Medispectra, Inc. Spectral volume microprobe for analysis of materials
US6148114A (en) 1996-11-27 2000-11-14 Ultrapointe Corporation Ring dilation and erosion techniques for digital image processing
US6847490B1 (en) 1997-01-13 2005-01-25 Medispectra, Inc. Optical probe accessory device for use in vivo diagnostic procedures
US6826422B1 (en) 1997-01-13 2004-11-30 Medispectra, Inc. Spectral volume microprobe arrays
US6684092B2 (en) 1997-02-24 2004-01-27 Lucid, Inc. System for facilitating pathological examination of a lesion in tissue
US6831994B2 (en) 1997-05-23 2004-12-14 Lynx Therapeutics, Inc. System and apparatus for sequential processing of analytes
US20090143244A1 (en) * 1997-05-23 2009-06-04 Solexa, Inc. System and apparatus for sequential processing of analytes
US8361713B2 (en) 1997-05-23 2013-01-29 Illumina, Inc. System and apparatus for sequential processing of analytes
US20020133073A1 (en) * 1998-12-23 2002-09-19 Nordstrom Robert J. Spectroscopic system employing a plurality of data types
US20020177777A1 (en) * 1998-12-23 2002-11-28 Medispectra, Inc. Optical methods and systems for rapid screening of the cervix
US20050033186A1 (en) * 1998-12-23 2005-02-10 Medispectra, Inc. Substantially monostatic, substantially confocal optical systems for examination of samples
US6411838B1 (en) 1998-12-23 2002-06-25 Medispectra, Inc. Systems and methods for optical examination of samples
US6760613B2 (en) 1998-12-23 2004-07-06 Medispectra, Inc. Substantially monostatic, substantially confocal optical systems for examination of samples
US6385484B2 (en) 1998-12-23 2002-05-07 Medispectra, Inc. Spectroscopic system employing a plurality of data types
US7127282B2 (en) 1998-12-23 2006-10-24 Medispectra, Inc. Optical methods and systems for rapid screening of the cervix
US9128024B2 (en) 1999-02-17 2015-09-08 Caliber Imaging & Diagnostics, Inc. Tissue specimen holder
US20020101655A1 (en) * 1999-02-17 2002-08-01 Greenwald Roger J. Tissue specimen holder
US20050157386A1 (en) * 1999-02-17 2005-07-21 Greenwald Roger J. Tissue specimen holder
US9052523B2 (en) 1999-02-17 2015-06-09 Caliber Imaging & Diagnostics, Inc. Cassette for facilitating optical sectioning of a retained tissue specimen
US20020154399A1 (en) * 1999-02-17 2002-10-24 Eastman Jay M. Cassette for facilitating optical sectioning of a retained tissue specimen
US8149506B2 (en) 1999-02-17 2012-04-03 Lucii, Inc. Cassette for facilitating optical sectioning of a retained tissue specimen
US9772486B2 (en) 1999-02-17 2017-09-26 Caliber Imaging & Diagnostics, Inc. System for optically sectioning a tissue specimen
US6856458B2 (en) 1999-02-17 2005-02-15 Lucid, Inc. Tissue specimen holder
US6615141B1 (en) 1999-05-14 2003-09-02 Cytokinetics, Inc. Database system for predictive cellular bioinformatics
US6743576B1 (en) 1999-05-14 2004-06-01 Cytokinetics, Inc. Database system for predictive cellular bioinformatics
US6738716B1 (en) 1999-05-14 2004-05-18 Cytokinetics, Inc. Database system for predictive cellular bioinformatics
US6651008B1 (en) 1999-05-14 2003-11-18 Cytokinetics, Inc. Database system including computer code for predictive cellular bioinformatics
US20060228016A1 (en) * 1999-05-14 2006-10-12 Cytokinetics, Inc. Image analysis of the golgi complex
US6631331B1 (en) * 1999-05-14 2003-10-07 Cytokinetics, Inc. Database system for predictive cellular bioinformatics
US20050056783A1 (en) * 1999-07-01 2005-03-17 General Nanotechnology, Llc Object inspection and/or modification system and method
US7109482B2 (en) 1999-07-01 2006-09-19 General Nanotechnology Llc Object inspection and/or modification system and method
US20020197728A1 (en) * 1999-12-15 2002-12-26 Howard Kaufman Methods of monitoring effects of chemical agents on a sample
US20030144585A1 (en) * 1999-12-15 2003-07-31 Howard Kaufman Image processing using measures of similarity
US20050064602A1 (en) * 1999-12-15 2005-03-24 Medispectra, Inc. Methods of monitoring effects of chemical agents on a sample
US7187810B2 (en) 1999-12-15 2007-03-06 Medispectra, Inc. Methods and systems for correcting image misalignment
US7260248B2 (en) 1999-12-15 2007-08-21 Medispectra, Inc. Image processing using measures of similarity
US20020127735A1 (en) * 1999-12-15 2002-09-12 Howard Kaufman Methods of monitoring effects of chemical agents on a sample
US6902935B2 (en) 1999-12-15 2005-06-07 Medispectra, Inc. Methods of monitoring effects of chemical agents on a sample
US20030207250A1 (en) * 1999-12-15 2003-11-06 Medispectra, Inc. Methods of diagnosing disease
US20020049544A1 (en) * 2000-06-23 2002-04-25 Cytokinetics, Inc. Image analysis for phenotyping sets of mutant cells
US7194118B1 (en) * 2000-11-10 2007-03-20 Lucid, Inc. System for optically sectioning and mapping surgically excised tissue
US6876760B1 (en) 2000-12-04 2005-04-05 Cytokinetics, Inc. Classifying cells based on information contained in cell images
US20050272073A1 (en) * 2000-12-04 2005-12-08 Cytokinetics, Inc., A Delaware Corporation Ploidy classification method
US7218764B2 (en) 2000-12-04 2007-05-15 Cytokinetics, Inc. Ploidy classification method
US6839661B2 (en) 2000-12-15 2005-01-04 Medispectra, Inc. System for normalizing spectra
US6599694B2 (en) 2000-12-18 2003-07-29 Cytokinetics, Inc. Method of characterizing potential therapeutics by determining cell-cell interactions
US20050115047A1 (en) * 2001-01-30 2005-06-02 General Nanotechnology Llc Manufacturing of micro-objects such as miniature diamond tool tips
US6865927B1 (en) 2001-01-30 2005-03-15 General Nanotechnology Llc Sharpness testing of micro-objects such as miniature diamond tool tips
US6931710B2 (en) 2001-01-30 2005-08-23 General Nanotechnology Llc Manufacturing of micro-objects such as miniature diamond tool tips
US6956961B2 (en) 2001-02-20 2005-10-18 Cytokinetics, Inc. Extracting shape information contained in cell images
US7151847B2 (en) 2001-02-20 2006-12-19 Cytokinetics, Inc. Image analysis of the golgi complex
US7016787B2 (en) 2001-02-20 2006-03-21 Cytokinetics, Inc. Characterizing biological stimuli by response curves
US7269278B2 (en) 2001-02-20 2007-09-11 Cytokinetics, Inc. Extracting shape information contained in cell images
US20050267690A1 (en) * 2001-02-20 2005-12-01 Cytokinetics, Inc., A Delaware Corporation Extracting shape information contained in cell images
US20020141631A1 (en) * 2001-02-20 2002-10-03 Cytokinetics, Inc. Image analysis of the golgi complex
US7657076B2 (en) 2001-02-20 2010-02-02 Cytokinetics, Inc. Characterizing biological stimuli by response curves
US6787768B1 (en) 2001-03-08 2004-09-07 General Nanotechnology Llc Method and apparatus for tool and tip design for nanomachining and measurement
US6880388B1 (en) 2001-03-08 2005-04-19 General Nanotechnology Llc Active cantilever for nanomachining and metrology
US7253407B1 (en) 2001-03-08 2007-08-07 General Nanotechnology Llc Active cantilever for nanomachining and metrology
US7196328B1 (en) 2001-03-08 2007-03-27 General Nanotechnology Llc Nanomachining method and apparatus
US7178387B1 (en) 2001-03-08 2007-02-20 General Nanotechnology Llc Method and apparatus for scanning in scanning probe microscopy and presenting results
US7947952B1 (en) 2001-03-08 2011-05-24 General Nanotechnology Llc Nanomachining method and apparatus
US6752008B1 (en) 2001-03-08 2004-06-22 General Nanotechnology Llc Method and apparatus for scanning in scanning probe microscopy and presenting results
US7137292B1 (en) 2001-03-08 2006-11-21 General Nanotechnology Llc Active cantilever for nanomachining and metrology
US6923044B1 (en) 2001-03-08 2005-08-02 General Nanotechnology Llc Active cantilever for nanomachining and metrology
US6802646B1 (en) 2001-04-30 2004-10-12 General Nanotechnology Llc Low-friction moving interfaces in micromachines and nanomachines
US20050058384A1 (en) * 2001-04-30 2005-03-17 General Nanotechnology Llc Low-friction moving interfaces in micromachines and nanomachines
US7547882B2 (en) 2001-10-19 2009-06-16 Rave Llc Scan data collection for better overall data accurancy
US7053369B1 (en) 2001-10-19 2006-05-30 Rave Llc Scan data collection for better overall data accuracy
US20060174384A1 (en) * 2001-10-19 2006-08-03 Rave Llc Scan data collection for better overall data accurancy
US7266998B2 (en) 2001-11-28 2007-09-11 General Nanotechnology Llc Method and apparatus for micromachines, microstructures, nanomachines and nanostructures
US20050172739A1 (en) * 2001-11-28 2005-08-11 General Nanotechnology Llc Method and apparatus for micromachines, microstructures, nanomachines and nanostructures
US6813937B2 (en) 2001-11-28 2004-11-09 General Nanotechnology Llc Method and apparatus for micromachines, microstructures, nanomachines and nanostructures
US7631549B1 (en) 2001-11-28 2009-12-15 General Nanotechnology Llc Method and apparatus for micromachines, microstructures, nanomachines and nanostructures
US9075082B2 (en) 2002-03-07 2015-07-07 Victor B. Kley Fluid delivery for scanning probe microscopy
US6818903B2 (en) 2002-07-09 2004-11-16 Medispectra, Inc. Method and apparatus for identifying spectral artifacts
US20040007674A1 (en) * 2002-07-09 2004-01-15 Schomacker Kevin T. Method and apparatus for identifying spectral artifacts
US20040214156A1 (en) * 2002-07-09 2004-10-28 Medispectra, Inc. Method and apparatus for identifying spectral artifacts
US6933154B2 (en) 2002-07-09 2005-08-23 Medispectra, Inc. Optimal windows for obtaining optical data for characterization of tissue samples
US7282723B2 (en) 2002-07-09 2007-10-16 Medispectra, Inc. Methods and apparatus for processing spectral data for use in tissue characterization
US20080091110A1 (en) * 2002-07-10 2008-04-17 Zelenchuk Alex R Fluorescent Fiberoptic Probe for Tissue Health Discrimination and Method of Use Thereof
US8005527B2 (en) 2002-07-10 2011-08-23 Luma Imaging Corporation Method of determining a condition of a tissue
US7103401B2 (en) 2002-07-10 2006-09-05 Medispectra, Inc. Colonic polyp discrimination by tissue fluorescence and fiberoptic probe
US20050043635A1 (en) * 2002-07-10 2005-02-24 Medispectra, Inc. Fluorescent fiberoptic probe for tissue health discrimination and method of use thereof
US7310547B2 (en) 2002-07-10 2007-12-18 Medispectra, Inc. Fluorescent fiberoptic probe for tissue health discrimination
US6768918B2 (en) 2002-07-10 2004-07-27 Medispectra, Inc. Fluorescent fiberoptic probe for tissue health discrimination and method of use thereof
US20040118192A1 (en) * 2002-09-09 2004-06-24 General Nanotechnology Llc Fluid delivery for scanning probe microscopy
US6998689B2 (en) 2002-09-09 2006-02-14 General Nanotechnology Llc Fluid delivery for scanning probe microscopy
US8369591B2 (en) 2003-04-11 2013-02-05 Carl Zeiss Microimaging Gmbh Silhouette image acquisition
US20040206882A1 (en) * 2003-04-18 2004-10-21 Medispectra, Inc. Methods and apparatus for evaluating image focus
US7459696B2 (en) 2003-04-18 2008-12-02 Schomacker Kevin T Methods and apparatus for calibrating spectral data
US7469160B2 (en) 2003-04-18 2008-12-23 Banks Perry S Methods and apparatus for evaluating image focus
US20040208390A1 (en) * 2003-04-18 2004-10-21 Medispectra, Inc. Methods and apparatus for processing image data for use in tissue characterization
US20040208385A1 (en) * 2003-04-18 2004-10-21 Medispectra, Inc. Methods and apparatus for visually enhancing images
US20040209237A1 (en) * 2003-04-18 2004-10-21 Medispectra, Inc. Methods and apparatus for characterization of tissue samples
US7309867B2 (en) 2003-04-18 2007-12-18 Medispectra, Inc. Methods and apparatus for characterization of tissue samples
US7136518B2 (en) 2003-04-18 2006-11-14 Medispectra, Inc. Methods and apparatus for displaying diagnostic data
US20060228695A1 (en) * 2003-07-18 2006-10-12 Cytokinetics, Inc. Predicting hepatotoxicity using cell based assays
US7246012B2 (en) 2003-07-18 2007-07-17 Cytokinetics, Inc. Characterizing biological stimuli by response curves
US20050137806A1 (en) * 2003-07-18 2005-06-23 Cytokinetics, Inc. A Delaware Corporation Characterizing biological stimuli by response curves
US7817840B2 (en) 2003-07-18 2010-10-19 Cytokinetics, Inc. Predicting hepatotoxicity using cell based assays
US20060234332A1 (en) * 2003-07-18 2006-10-19 Cytokinetics, Inc. Predicting hepatotoxicity using cell based assays
US7235353B2 (en) 2003-07-18 2007-06-26 Cytokinetics, Inc. Predicting hepatotoxicity using cell based assays
US20050273271A1 (en) * 2004-04-05 2005-12-08 Aibing Rao Method of characterizing cell shape
US20070031818A1 (en) * 2004-07-15 2007-02-08 Cytokinetics, Inc., A Delaware Corporation Assay for distinguishing live and dead cells
US20060014135A1 (en) * 2004-07-15 2006-01-19 Cytokinetics, Inc. Assay for distinguishing live and dead cells
US7323318B2 (en) 2004-07-15 2008-01-29 Cytokinetics, Inc. Assay for distinguishing live and dead cells
US20060239329A1 (en) * 2005-03-14 2006-10-26 Kabushiki Kaisha Bio Echo Net Ear-type clinical thermometer
US7864996B2 (en) 2006-02-17 2011-01-04 Lucid, Inc. System for macroscopic and confocal imaging of tissue
US20070206275A1 (en) * 2006-02-17 2007-09-06 Paul Hemmer System for macroscopic and confocal imaging of tissue
EP1873232A1 (en) 2006-06-29 2008-01-02 Fujitsu Limited Microinjection apparatus and automatic focal point adjustment method
US8725477B2 (en) 2008-04-10 2014-05-13 Schlumberger Technology Corporation Method to generate numerical pseudocores using borehole images, digital rock samples, and multi-point statistics
US20090259446A1 (en) * 2008-04-10 2009-10-15 Schlumberger Technology Corporation Method to generate numerical pseudocores using borehole images, digital rock samples, and multi-point statistics
US9581723B2 (en) 2008-04-10 2017-02-28 Schlumberger Technology Corporation Method for characterizing a geological formation traversed by a borehole
US8311788B2 (en) 2009-07-01 2012-11-13 Schlumberger Technology Corporation Method to quantify discrete pore shapes, volumes, and surface areas using confocal profilometry
US20110004447A1 (en) * 2009-07-01 2011-01-06 Schlumberger Technology Corporation Method to build 3D digital models of porous media using transmitted laser scanning confocal mircoscopy and multi-point statistics
US20110004448A1 (en) * 2009-07-01 2011-01-06 Schlumberger Technology Corporation Method to quantify discrete pore shapes, volumes, and surface areas using confocal profilometry
US9229210B2 (en) 2012-02-26 2016-01-05 Caliber Imaging And Diagnostics, Inc. Tissue specimen stage for an optical sectioning microscope

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