US20030031781A1 - Broadband absorbing film for laser capture microdissection - Google Patents
Broadband absorbing film for laser capture microdissection Download PDFInfo
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- US20030031781A1 US20030031781A1 US10/264,420 US26442002A US2003031781A1 US 20030031781 A1 US20030031781 A1 US 20030031781A1 US 26442002 A US26442002 A US 26442002A US 2003031781 A1 US2003031781 A1 US 2003031781A1
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/2813—Producing thin layers of samples on a substrate, e.g. smearing, spinning-on
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/2813—Producing thin layers of samples on a substrate, e.g. smearing, spinning-on
- G01N2001/2833—Collecting samples on a sticky, tacky, adhesive surface
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/2813—Producing thin layers of samples on a substrate, e.g. smearing, spinning-on
- G01N2001/2833—Collecting samples on a sticky, tacky, adhesive surface
- G01N2001/284—Collecting samples on a sticky, tacky, adhesive surface using local activation of adhesive, i.e. Laser Capture Microdissection
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/31504—Composite [nonstructural laminate]
- Y10T428/31855—Of addition polymer from unsaturated monomers
Definitions
- the present invention relates to laser capture microdissection. More particularly, the present invention relates to broadband absorbing films for use in laser capture microdissection.
- the LCM technique is generally described in the recently published article: Laser Capture Microdissection, Science, Volume 274, Number 5289, Issue 8, pp 998-1001, published in 1996, incorporated herein by reference.
- the purpose of the LCM technique is to provide a simple method for the procurement of selected human cells from a heterogeneous population contained on a typical histopathology biopsy slide.
- a typical tissue biopsy sample consists of a 5 to 10 micron slice of tissue that is placed on a glass microscope slide using techniques well known in the field of pathology. This tissue slice is a cross section of the body organ that is being studied. The tissue consists of a variety of different types of cells. Often a pathologist desires to remove only a small portion of the tissue for further analysis.
- LCM employs a thermoplastic transfer film that is placed on top of the tissue sample.
- This film is manufactured containing organic dyes that are chosen to selectively absorb in the near infrared region of the spectrum overlapping the emission region of common AlGaAs laser diodes.
- organic dyes that are chosen to selectively absorb in the near infrared region of the spectrum overlapping the emission region of common AlGaAs laser diodes.
- Thermoplastic transfer films such as a 100 micron thick ethyl vinyl acetate (EVA) film available from Electroseal Corporation of Pompton Lakes, N.J. (type E540) have been used in LCM applications.
- EVA ethyl vinyl acetate
- the film is chosen to have a low melting point of about 90 C.
- thermoplastic EVA films used in LCM techniques have been doped with dyes, such as an infrared napthalocyanine dye, available from Aldrich Chemical Company (dye number 43296-2 or 39317-7). These dyes have a strong absorption in the 800 nm region, a wavelength region that overlaps with laser emitters used to selectively melt the film.
- the dye is mixed with the melted bulk plastic at an elevated temperature.
- the dyed plastic is then manufactured into a film using standard film manufacturing techniques.
- the dye concentration in the plastic is about 0.001M.
- the organic dyes which are used to alter the absorption characteristics of the films may have detrimental photochemistry effects in some cases. This could result in contamination of LCM samples.
- the organic dyes employed to date are sensitive to the wavelength of the incident laser light and thus the film must be matched to the laser employed.
- Yet another object of the present invention is to provide an LCM film which is very thin and can have very high optical absorption.
- a further object of the present invention is to provide an optical quality LCM film, which is not sensitive to the wavelength of the incident laser light.
- a further object of the present invention is to provide optical quality LCM films of adjustable thickness.
- Another object of the present invention is to provide an LCM film whose optical density can be adjusted so that sufficient light is transmitted through the sample to permit the sample to be viewed with back light illumination.
- Yet another object of the present invention is to provide an LCM film, which does not use an organic dye that might have detrimental photochemistry effects.
- Yet another object of the present invention is to provide an LCM film, which does not employ an organic dye, which does not have to be dissolved into the EVA polymer at high concentrations.
- thermoplastic film for LCM tissue transfer is thermally coupled to a broadband energy-absorbing material.
- the broadband energy-absorbing material may either be introduced into the film composition as a dopant or may be in thermal contact with the film.
- a film for LCM tissue transfer comprises a layer of a transparent support film; a layer of a broadband absorbing film; and a layer of a low temperature thermoplastic; the absorbing film having an overall thickness chosen to absorb a desired fraction of incident laser light.
- the film consists of a sandwich of layers containing a transparent support film such as mylar or polyester, a broadband absorbing film such as a metal film of nichrome or titanium, and a low temperature thermoplastic layer such as ethyl vinyl alcohol (EVA).
- a transparent support film such as mylar or polyester
- a broadband absorbing film such as a metal film of nichrome or titanium
- a low temperature thermoplastic layer such as ethyl vinyl alcohol (EVA).
- EVA ethyl vinyl alcohol
- a method for fabricating a multilayer film for LCM tissue transfer comprises the steps of: providing a support layer; forming a thin layer of a broadband absorbing film onto the support layer, the broadband absorbing film having a thickness chosen to absorb a desired fraction of incident laser light; and coating the broadband absorbing film with a layer of thermoplastic.
- one embodiment of the film is fabricated by evaporating a thin layer of metal film onto the polyester support using a deposition technique such as sputtering.
- the film thickness is chosen so as to absorb a desired fraction of incident laser light, usually between 10% and 95%.
- the metal thickness is adjusted to provide this optical density by controlling the length of time of the sputtering deposition process.
- the polyester/metal film is then coated with a thin layer (a few to 100 microns) of EVA thermoplastic using a spin coater to achieve a uniform layer across the surface. The spin coating process can be repeated several times to adjust the thickness of the EVA film.
- thermoplastic film is doped with a broadband energy-absorbing material.
- the dopant concentration is adjusted so as to give a suitable absorption, usually between 10% and 95%, for the desired thickness of EVA film.
- a broadband absorbing material is deposited on a substrate such as a cap for a biological analysis vessel.
- the metal film is deposited onto the bottom of a cap and then the cap is coated with EVA using the process that is disclosed in the prior application.
- FIG. 1 is a cross sectional view of an LCM tissue transfer film in a multiplayer structure according to a first embodiment of the present invention.
- FIG. 2 is a cross sectional view of an LCM tissue transfer film in a multilayer structure according to a second embodiment of the present invention.
- FIG. 3 is a cross sectional view of an LCM tissue transfer film according to a second embodiment of the present invention wherein a broadband energy-absorbing material is doped into the transfer film.
- FIG. 4 is a cross sectional view of an LCM tissue transfer film according to a second embodiment of the present invention wherein a broadband energy-absorbing material is formed on a substrate.
- FIG. 5 is a perspective view of a cap for an analysis vessel showing a procedure for affixing the LCM film thereto.
- FIG. 6 is a perspective view of a cap for an analysis vessel showing an alternate procedure for affixing the LCM film thereto.
- EVA ethyl vinyl acetate
- the present invention comprises an LCM film employing a broadband energy-absorbing material either doped into the layer of transfer film material or as a film in thermal contact with the layer of transfer film material.
- the broadband absorber should have a relatively broad absorption line throughout the visible region of the spectrum so that the absorber does not effect the color spectrum of the transmitted light that is used to illuminate the sample.
- Metal films such as nichrome or titanium are examples of a broadband absorber that can be deposited on a surface, which can be thermally coupled to the transfer film.
- Thermal coupling to the transfer film may be accomplished by evaporating a thin layer of broadband absorbing film onto a transparent support film such as mylar or polyester.
- FIG. 1 a cross sectional view of an LCM tissue transfer film 10 according to a first embodiment of the present invention is presented.
- the film 10 consists of a sandwich of layers including a transparent support film 12 such as mylar or polyester, a broadband absorbing film 14 such as a metal film of nichrome or titanium, and a low temperature thermoplastic layer 16 such as EVA.
- the transparent support layer may have a thickness of between about 25 microns and about 250 microns.
- the thickness of the broadband absorbing film is chosen so as to absorb a desired fraction of incident laser light.
- a typical film may absorb from about 10% to about 95% of the incident light.
- the metal thickness is adjusted to provide this optical density by controlling the length of time of the sputtering deposition process.
- the film 10 of FIG. 1 is fabricated by evaporating a thin layer of broadband absorbing film onto the support film using a deposition technique such as sputtering as is known in the art.
- a deposition technique such as sputtering as is known in the art.
- Another method for depositing metal film coatings is to use electron beam evaporation methods, which are well known in the art.
- the appropriate thickness of the metal film can be determined by monitoring the film deposition process using a witness sample that allows measurement of the optical transmission of the film as a function of deposition time. The deposition is halted when the appropriate transmission level is reached. This is a procedure that is well known to those skilled in the art of thin film coating.
- the support and broadband absorbing film sandwich is then coated with a thin layer (between a few microns and about 100 microns) of EVA thermoplastic using a spin coater to achieve a uniform layer across the piece.
- the spin coating process can be repeated several times to adjust the thickness of the EVA transfer film.
- the EVA material may be dissolved in a solvent such as methylene chloride to reduce its viscosity as is well known to those of ordinary skill in the art.
- the film 20 consists of a sandwich of layers including a transparent support film 22 such as mylar or polyester, a first low temperature thermoplastic layer 24 such as EVA, a broadband absorbing film 26 such as a metal film of nichrome or titanium, and a second low temperature thermoplastic layer 28 such as EVA.
- a transparent support film 22 such as mylar or polyester
- a first low temperature thermoplastic layer 24 such as EVA
- a broadband absorbing film 26 such as a metal film of nichrome or titanium
- a second low temperature thermoplastic layer 28 such as EVA.
- the process for making the film of FIG. 2 is similar to that used to make the film of FIG. 1.
- the additional EVA layer may be formed by a spin-on process.
- the EVA side of the film of either FIGS. 1 or 2 is placed in contact with a thin tissue sample.
- Laser light is focused on the sandwich structure and the light is absorbed by the thin, metal film, which raises the temperature of the EVA film and melts the portion of the EVA that is in contact with the region of the metal film that is exposed to the focused laser beam.
- the laser power is chosen that the temperature rise does not melt the polyester support film.
- typical laser powers are on the order of 50 mW for film transmissions of about 10%.
- the melted EVA area adheres to tissue samples, which can then be excised by removing the film.
- FIG. 3 a cross sectional view is presented of an LCM tissue transfer film 30 according to a second embodiment of the present invention wherein a broadband energy-absorbing material is doped into the transfer film.
- the broadband energy-absorbing material is illustrated as shaded region 32 .
- An example of a broadband absorber that can be used to dope the EVA plastic is the chemical substance Buckminsterfullerene available as product #379646 from Sigma Chemical Company of St. Louis, Mo. This substance is a pure carbon compound comprising submicron particles that have very broad absorption profiles in the visible region of the spectrum.
- the Buckminsterfullerene can be mixed with heated EVA and the concentration adjusted so as to give a suitable absorption, usually between 10% and 95%, for the desired thickness of EVA film.
- the advantage of this method of doping the film is that, unlike the prior art LCM transfer films containing organic dyes, a specific laser wavelength is not required for activation and the extinction coefficient of the Buckminsterfullerene is very high. Moreover, photochemical effects should be reduced compared to those produced using an organic dye.
- FIG. 4 is a cross sectional view of an embodiment of the present invention wherein a broadband energy-absorbing material 40 is formed on a substrate 42 and a thermoplastic LCM transfer film 44 is affixed to the surface of the broadband energy-absorbing material.
- the broadband energy-absorbing material 40 is preferably a metal film such as nichrome or titanium.
- substrate 42 is in the shape of a cap for a biological analysis vessel as disclosed in co-pending application Ser. No. ______ filed Feb. 7, 1997, entitled “LASER CAPTURE MICRODISSECTION ANALYSIS VESSEL” expressly incorporated herein by reference.
- the biological analysis vessel may be a vessel such as an eppindorf tube or other well-known vessel.
- FIG. 5 is a perspective view of a cap 42 for an analysis vessel illustrating a step in a first procedure for affixing the LCM film thereto.
- cap 42 is equipped with a marking means such as a UPC label or laser etched label. Serializing all of the caps provides for easy identification and tracking of cell samples.
- the label may be read by a sensor, such as a UPC label sensor or OCR sensor, which is mounted in or on the laser capture microdissection apparatus.
- the serial number is placed on the top of the cap.
- the serial number is placed on the top of cap 42 , and the thickness of cap 42 is selected to be larger than the depth of field of the microscope objective of the LCM apparatus with which cap 42 will be used.
- the microscope can be focused on the tissue sample below the bottom surface of the cap and not have the label or serial number interfere optically, since the label is far from the focal plane of the imaging lens and is thus out of focus.
- the LCM transfer film 44 may be affixed to the surface of the caps according to the present invention.
- a small, e.g., about 1 cm square piece of thermoplastic film 44 is cut.
- the film 44 is gently pressed onto the bottom surface of the cap 42 making it stick thereto.
- a glass microscope slide 46 is heated to about 100 C on a hot plate.
- a 0.002 inch thick piece of mylar plastic release liner 48 is placed on the slide.
- a release liner is a plastic sheet that is coated with a silicone coating so it does not stick to the thermoplastic film material or the glass slide.
- the cap 42 with its attached film 44 is pressed onto the release liner/slide assembly for about 5 seconds or until the film melts.
- the cap 42 with attached film 44 and release liner 48 is then removed from the hot glass slide 46 , cooled down to room temperature, and the release liner 48 is peeled off. Finally, the excess thermoplastic film is trimmed off.
- FIG. 6 is a perspective view of a cap for an analysis vessel showing an alternate procedure for affixing the LCM film thereto.
- a piece of transparent double-sided adhesive tape 50 (such as standard double stick tape available from 3M Corporation) may be used to tape the thermoplastic film 44 to the bottom of the cap 42 . The excess thermoplastic film may then be trimmed off.
- the metal film layer can be very thin and still have very high optical absorption.
- the spin coating process gives optical quality films of adjustable thickness.
- the film of the present invention is not sensitive to the wavelength of the incident laser light as are the prior art dye impregnated films.
- the broadband energy-absorbing material may be isolated from the tissue sample by the EVA transfer film layer.
- the broadband energy-absorbing material of the present invention does not use an organic dye that might have detrimental photochemistry effects on the sample with which it is in contact.
- the metal film does not have to be dissolved into the EVA polymer at high concentrations like an organic dye in the prior art films.
Abstract
Description
- This application is a divisional of U.S. patent application Ser. No. 08/800,882, filed on Feb. 14, 1997, the contents of which is incorporated herein by reference in its entirety.
- 1. Field of the Invention
- The present invention relates to laser capture microdissection. More particularly, the present invention relates to broadband absorbing films for use in laser capture microdissection.
- 2. The Prior Art
- The LCM technique is generally described in the recently published article: Laser Capture Microdissection, Science, Volume 274, Number 5289, Issue 8, pp 998-1001, published in 1996, incorporated herein by reference. The purpose of the LCM technique is to provide a simple method for the procurement of selected human cells from a heterogeneous population contained on a typical histopathology biopsy slide.
- A typical tissue biopsy sample consists of a 5 to 10 micron slice of tissue that is placed on a glass microscope slide using techniques well known in the field of pathology. This tissue slice is a cross section of the body organ that is being studied. The tissue consists of a variety of different types of cells. Often a pathologist desires to remove only a small portion of the tissue for further analysis.
- LCM employs a thermoplastic transfer film that is placed on top of the tissue sample. This film is manufactured containing organic dyes that are chosen to selectively absorb in the near infrared region of the spectrum overlapping the emission region of common AlGaAs laser diodes. When the film is exposed to the focused laser beam the exposed region is heated by the laser and melts, adhering to the tissue in the region that was exposed. The film is then lifted from the tissue and the selected portion of the tissue is removed with the film.
- Thermoplastic transfer films such as a 100 micron thick ethyl vinyl acetate (EVA) film available from Electroseal Corporation of Pompton Lakes, N.J. (type E540) have been used in LCM applications. The film is chosen to have a low melting point of about 90 C.
- The thermoplastic EVA films used in LCM techniques have been doped with dyes, such as an infrared napthalocyanine dye, available from Aldrich Chemical Company (dye number 43296-2 or 39317-7). These dyes have a strong absorption in the 800 nm region, a wavelength region that overlaps with laser emitters used to selectively melt the film. The dye is mixed with the melted bulk plastic at an elevated temperature. The dyed plastic is then manufactured into a film using standard film manufacturing techniques. The dye concentration in the plastic is about 0.001M.
- While the films employed in LCM applications have proved satisfactory for the task, they have several drawbacks. The optical absorption of a dye impregnated film is a function of its thickness. This property of the film may be in conflict with a desire to select film thickness for other reasons.
- The organic dyes which are used to alter the absorption characteristics of the films may have detrimental photochemistry effects in some cases. This could result in contamination of LCM samples. In addition, the organic dyes employed to date are sensitive to the wavelength of the incident laser light and thus the film must be matched to the laser employed.
- It is therefore an object of the invention to provide a film for LCM applications, which overcomes the shortcomings of the prior art.
- It is another object of the present invention to provide a simple LCM film to be used in an LCM instrument.
- Yet another object of the present invention is to provide an LCM film which is very thin and can have very high optical absorption.
- A further object of the present invention is to provide an optical quality LCM film, which is not sensitive to the wavelength of the incident laser light.
- A further object of the present invention is to provide optical quality LCM films of adjustable thickness.
- Another object of the present invention is to provide an LCM film whose optical density can be adjusted so that sufficient light is transmitted through the sample to permit the sample to be viewed with back light illumination.
- Yet another object of the present invention is to provide an LCM film, which does not use an organic dye that might have detrimental photochemistry effects.
- Yet another object of the present invention is to provide an LCM film, which does not employ an organic dye, which does not have to be dissolved into the EVA polymer at high concentrations.
- A thermoplastic film for LCM tissue transfer is thermally coupled to a broadband energy-absorbing material. The broadband energy-absorbing material may either be introduced into the film composition as a dopant or may be in thermal contact with the film.
- According to one embodiment of the present invention, a film for LCM tissue transfer comprises a layer of a transparent support film; a layer of a broadband absorbing film; and a layer of a low temperature thermoplastic; the absorbing film having an overall thickness chosen to absorb a desired fraction of incident laser light.
- According to this embodiment of the invention, the film consists of a sandwich of layers containing a transparent support film such as mylar or polyester, a broadband absorbing film such as a metal film of nichrome or titanium, and a low temperature thermoplastic layer such as ethyl vinyl alcohol (EVA). The metal film thickness is chosen so as to absorb a desired fraction of incident laser light. A typical film may absorb say 10% to 90% of the incident light. The metal thickness is adjusted to provide this optical density by controlling the length of time of the sputtering deposition process. The metal absorbing layer can be sandwiched between two layers of EVA if desired.
- A method for fabricating a multilayer film for LCM tissue transfer comprises the steps of: providing a support layer; forming a thin layer of a broadband absorbing film onto the support layer, the broadband absorbing film having a thickness chosen to absorb a desired fraction of incident laser light; and coating the broadband absorbing film with a layer of thermoplastic.
- According to the method of the present invention, one embodiment of the film is fabricated by evaporating a thin layer of metal film onto the polyester support using a deposition technique such as sputtering. The film thickness is chosen so as to absorb a desired fraction of incident laser light, usually between 10% and 95%. The metal thickness is adjusted to provide this optical density by controlling the length of time of the sputtering deposition process. The polyester/metal film is then coated with a thin layer (a few to 100 microns) of EVA thermoplastic using a spin coater to achieve a uniform layer across the surface. The spin coating process can be repeated several times to adjust the thickness of the EVA film.
- According to one embodiment of the present invention, a thermoplastic film is doped with a broadband energy-absorbing material. The dopant concentration is adjusted so as to give a suitable absorption, usually between 10% and 95%, for the desired thickness of EVA film.
- According to another embodiment of the present invention, a broadband absorbing material is deposited on a substrate such as a cap for a biological analysis vessel. The metal film is deposited onto the bottom of a cap and then the cap is coated with EVA using the process that is disclosed in the prior application.
- FIG. 1 is a cross sectional view of an LCM tissue transfer film in a multiplayer structure according to a first embodiment of the present invention.
- FIG. 2 is a cross sectional view of an LCM tissue transfer film in a multilayer structure according to a second embodiment of the present invention.
- FIG. 3 is a cross sectional view of an LCM tissue transfer film according to a second embodiment of the present invention wherein a broadband energy-absorbing material is doped into the transfer film.
- FIG. 4 is a cross sectional view of an LCM tissue transfer film according to a second embodiment of the present invention wherein a broadband energy-absorbing material is formed on a substrate.
- FIG. 5 is a perspective view of a cap for an analysis vessel showing a procedure for affixing the LCM film thereto.
- FIG. 6 is a perspective view of a cap for an analysis vessel showing an alternate procedure for affixing the LCM film thereto.
- Those of ordinary skill in the art will realize that the following description of the present invention is illustrative only and not in any way limiting. Other embodiments of the invention will readily suggest themselves to such skilled persons.
- Reference is made in the following disclosure to ethyl vinyl acetate (EVA) film as the transfer film. Persons of ordinary skill in the art will recognize that other films having desirable properties for use as the transfer film may also be employed for that purpose and the disclosure is not intended to be limited to LCM films employing EVA transfer films.
- The present invention comprises an LCM film employing a broadband energy-absorbing material either doped into the layer of transfer film material or as a film in thermal contact with the layer of transfer film material. The broadband absorber should have a relatively broad absorption line throughout the visible region of the spectrum so that the absorber does not effect the color spectrum of the transmitted light that is used to illuminate the sample.
- Metal films, such as nichrome or titanium are examples of a broadband absorber that can be deposited on a surface, which can be thermally coupled to the transfer film. Thermal coupling to the transfer film may be accomplished by evaporating a thin layer of broadband absorbing film onto a transparent support film such as mylar or polyester.
- Referring first to FIG. 1, a cross sectional view of an LCM
tissue transfer film 10 according to a first embodiment of the present invention is presented. Thefilm 10 consists of a sandwich of layers including atransparent support film 12 such as mylar or polyester, abroadband absorbing film 14 such as a metal film of nichrome or titanium, and a lowtemperature thermoplastic layer 16 such as EVA. - The transparent support layer may have a thickness of between about 25 microns and about 250 microns. The thickness of the broadband absorbing film is chosen so as to absorb a desired fraction of incident laser light. A typical film may absorb from about 10% to about 95% of the incident light. The metal thickness is adjusted to provide this optical density by controlling the length of time of the sputtering deposition process.
- The
film 10 of FIG. 1 is fabricated by evaporating a thin layer of broadband absorbing film onto the support film using a deposition technique such as sputtering as is known in the art. Another method for depositing metal film coatings is to use electron beam evaporation methods, which are well known in the art. The appropriate thickness of the metal film can be determined by monitoring the film deposition process using a witness sample that allows measurement of the optical transmission of the film as a function of deposition time. The deposition is halted when the appropriate transmission level is reached. This is a procedure that is well known to those skilled in the art of thin film coating. - According to a presently preferred embodiment of the invention, the support and broadband absorbing film sandwich is then coated with a thin layer (between a few microns and about 100 microns) of EVA thermoplastic using a spin coater to achieve a uniform layer across the piece. The spin coating process can be repeated several times to adjust the thickness of the EVA transfer film. If necessary, the EVA material may be dissolved in a solvent such as methylene chloride to reduce its viscosity as is well known to those of ordinary skill in the art.
- Referring now to FIG. 2, a cross sectional view of an LCM
tissue transfer film 20 according to a second embodiment of the present invention is presented. Thefilm 20 consists of a sandwich of layers including atransparent support film 22 such as mylar or polyester, a first lowtemperature thermoplastic layer 24 such as EVA, abroadband absorbing film 26 such as a metal film of nichrome or titanium, and a second lowtemperature thermoplastic layer 28 such as EVA. - The process for making the film of FIG. 2 is similar to that used to make the film of FIG. 1. The additional EVA layer may be formed by a spin-on process.
- In use, the EVA side of the film of either FIGS.1 or 2 is placed in contact with a thin tissue sample. Laser light is focused on the sandwich structure and the light is absorbed by the thin, metal film, which raises the temperature of the EVA film and melts the portion of the EVA that is in contact with the region of the metal film that is exposed to the focused laser beam. The laser power is chosen that the temperature rise does not melt the polyester support film. For films contemplated by the present invention, typical laser powers are on the order of 50 mW for film transmissions of about 10%. The melted EVA area adheres to tissue samples, which can then be excised by removing the film.
- Referring now to FIG. 3, a cross sectional view is presented of an LCM
tissue transfer film 30 according to a second embodiment of the present invention wherein a broadband energy-absorbing material is doped into the transfer film. The broadband energy-absorbing material is illustrated as shadedregion 32. - An example of a broadband absorber that can be used to dope the EVA plastic is the chemical substance Buckminsterfullerene available as product #379646 from Sigma Chemical Company of St. Louis, Mo. This substance is a pure carbon compound comprising submicron particles that have very broad absorption profiles in the visible region of the spectrum. The Buckminsterfullerene can be mixed with heated EVA and the concentration adjusted so as to give a suitable absorption, usually between 10% and 95%, for the desired thickness of EVA film. The advantage of this method of doping the film is that, unlike the prior art LCM transfer films containing organic dyes, a specific laser wavelength is not required for activation and the extinction coefficient of the Buckminsterfullerene is very high. Moreover, photochemical effects should be reduced compared to those produced using an organic dye.
- FIG. 4 is a cross sectional view of an embodiment of the present invention wherein a broadband energy-absorbing
material 40 is formed on asubstrate 42 and a thermoplasticLCM transfer film 44 is affixed to the surface of the broadband energy-absorbing material. The broadband energy-absorbingmaterial 40 is preferably a metal film such as nichrome or titanium. As may be seen from FIG. 4,substrate 42 is in the shape of a cap for a biological analysis vessel as disclosed in co-pending application Ser. No. ______ filed Feb. 7, 1997, entitled “LASER CAPTURE MICRODISSECTION ANALYSIS VESSEL” expressly incorporated herein by reference. The biological analysis vessel may be a vessel such as an eppindorf tube or other well-known vessel. - FIG. 5 is a perspective view of a
cap 42 for an analysis vessel illustrating a step in a first procedure for affixing the LCM film thereto. Persons of ordinary skill in the art will observe thatcap 42 is equipped with a marking means such as a UPC label or laser etched label. Serializing all of the caps provides for easy identification and tracking of cell samples. The label may be read by a sensor, such as a UPC label sensor or OCR sensor, which is mounted in or on the laser capture microdissection apparatus. - According to this aspect of the present invention, the serial number is placed on the top of the cap. The serial number is placed on the top of
cap 42, and the thickness ofcap 42 is selected to be larger than the depth of field of the microscope objective of the LCM apparatus with which cap 42 will be used. Thus, the microscope can be focused on the tissue sample below the bottom surface of the cap and not have the label or serial number interfere optically, since the label is far from the focal plane of the imaging lens and is thus out of focus. - There are several ways in which the
LCM transfer film 44 may be affixed to the surface of the caps according to the present invention. As may be seen from FIG. 5, first, a small, e.g., about 1 cm square piece ofthermoplastic film 44 is cut. Thefilm 44 is gently pressed onto the bottom surface of thecap 42 making it stick thereto. Aglass microscope slide 46 is heated to about 100 C on a hot plate. A 0.002 inch thick piece of mylarplastic release liner 48 is placed on the slide. As is known in the art, a release liner is a plastic sheet that is coated with a silicone coating so it does not stick to the thermoplastic film material or the glass slide. - The
cap 42 with its attachedfilm 44 is pressed onto the release liner/slide assembly for about 5 seconds or until the film melts. Thecap 42 with attachedfilm 44 andrelease liner 48 is then removed from thehot glass slide 46, cooled down to room temperature, and therelease liner 48 is peeled off. Finally, the excess thermoplastic film is trimmed off. - FIG. 6 is a perspective view of a cap for an analysis vessel showing an alternate procedure for affixing the LCM film thereto. According to this method, a piece of transparent double-sided adhesive tape50 (such as standard double stick tape available from 3M Corporation) may be used to tape the
thermoplastic film 44 to the bottom of thecap 42. The excess thermoplastic film may then be trimmed off. - There are several advantages inherent in the LCM transfer film of the present invention. The metal film layer can be very thin and still have very high optical absorption. The spin coating process gives optical quality films of adjustable thickness. In addition, the film of the present invention is not sensitive to the wavelength of the incident laser light as are the prior art dye impregnated films.
- Another advantage of the present invention is that the broadband energy-absorbing material may be isolated from the tissue sample by the EVA transfer film layer. The broadband energy-absorbing material of the present invention does not use an organic dye that might have detrimental photochemistry effects on the sample with which it is in contact. Also, in embodiments of the present invention, which employ a metal film, the metal film does not have to be dissolved into the EVA polymer at high concentrations like an organic dye in the prior art films.
- While embodiments and applications of this invention have been shown and described, it would be apparent to those skilled in the art that many more modifications than mentioned above are possible without departing from the inventive concepts herein. The invention, therefore, is not to be restricted except in the spirit of the appended claims.
Claims (44)
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US10/264,420 US20030031781A1 (en) | 1997-02-14 | 2002-10-03 | Broadband absorbing film for laser capture microdissection |
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US08/800,882 US6495195B2 (en) | 1997-02-14 | 1997-02-14 | Broadband absorbing film for laser capture microdissection |
US10/264,420 US20030031781A1 (en) | 1997-02-14 | 2002-10-03 | Broadband absorbing film for laser capture microdissection |
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US10/264,420 Abandoned US20030031781A1 (en) | 1997-02-14 | 2002-10-03 | Broadband absorbing film for laser capture microdissection |
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AU (1) | AU6136598A (en) |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090054264A1 (en) * | 2006-02-27 | 2009-02-26 | Commissariat A L'energie Atomique | Method of Fabricating an Array of Capillaries on a Chip |
Families Citing this family (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6805918B2 (en) * | 1999-01-27 | 2004-10-19 | The United States Of America As Represented By The Secretary Of The Navy | Laser forward transfer of rheological systems |
US6815015B2 (en) * | 1999-01-27 | 2004-11-09 | The United States Of America As Represented By The Secretary Of The Navy | Jetting behavior in the laser forward transfer of rheological systems |
US6905738B2 (en) * | 1999-01-27 | 2005-06-14 | The United States Of America As Represented By The Secretary Of The Navy | Generation of viable cell active biomaterial patterns by laser transfer |
US6936311B2 (en) * | 1999-01-27 | 2005-08-30 | The United States Of America As Represented By The Secretary Of The Navy | Generation of biomaterial microarrays by laser transfer |
DE10003588C2 (en) | 2000-01-25 | 2002-10-02 | Sl Microtest Wissenschaftliche | Method of isolating part of a layer of biological material |
AU2001238462A1 (en) * | 2000-02-16 | 2001-08-27 | Arcturus Engineering, Inc. | Transfer film for laser microcapture |
DE10018251C2 (en) | 2000-04-13 | 2003-08-14 | Leica Microsystems | Laser cutting device with microscope |
DE10039979A1 (en) * | 2000-08-16 | 2002-03-07 | P A L M Gmbh | Carrier device for a preparation for separating individual objects from the preparation by means of laser radiation |
US8715955B2 (en) | 2004-09-09 | 2014-05-06 | Life Technologies Corporation | Laser microdissection apparatus and method |
US8346483B2 (en) * | 2002-09-13 | 2013-01-01 | Life Technologies Corporation | Interactive and automated tissue image analysis with global training database and variable-abstraction processing in cytological specimen classification and laser capture microdissection applications |
US7456938B2 (en) * | 2003-11-07 | 2008-11-25 | Mds Analytical Technologies (Us) Inc. | Laser microdissection on inverted polymer films |
US10156501B2 (en) | 2001-11-05 | 2018-12-18 | Life Technologies Corporation | Automated microdissection instrument for determining a location of a laser beam projection on a worksurface area |
US8722357B2 (en) | 2001-11-05 | 2014-05-13 | Life Technologies Corporation | Automated microdissection instrument |
DE102005061561A1 (en) | 2005-12-22 | 2007-06-28 | P.A.L.M. Microlaser Technologies Ag | Microdessection method for separation of e.g. individual cells, of e.g. biological preparation, involves cutting preparation through laser irradiation to divide cut layer into low cut and non cut sections, where non cut section is removed |
DE102006045620B4 (en) * | 2006-09-25 | 2009-10-29 | Roland Dr. Kilper | Device and method for receiving, transporting and storing microscopic samples |
US8076158B2 (en) * | 2008-05-05 | 2011-12-13 | Core Laboratories Lp | Enhanced process for preparing core sample thin sections |
CN101598940A (en) * | 2008-06-04 | 2009-12-09 | 北大方正集团有限公司 | A kind of data processing method and system |
US20110070597A1 (en) * | 2009-05-20 | 2011-03-24 | University Of Connecticut | Thin-Film Passive Samplers for Detection of Hydrophobic Organic Contaminants and Estrogenicity in Various Environments |
JP5775323B2 (en) * | 2011-02-23 | 2015-09-09 | 株式会社カプコン | Program and image processing apparatus provided with computer for executing the program |
JP2015517825A (en) * | 2012-05-29 | 2015-06-25 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニアThe Regents Of The University Of California | Systems, methods and components for separating cells from fluid samples |
WO2015053039A1 (en) * | 2013-10-07 | 2015-04-16 | 国立大学法人名古屋大学 | Laser microdissection device, analysis device containing laser microdissection device, and method for producing microchip |
EP3282241B1 (en) * | 2015-04-06 | 2019-12-11 | National University Corporation Nagoya University | Laser microdissection apparatus, analyzing apparatus including laser microdissection apparatus, sample collecting method, and device employed in laser microdissection apparatus |
DE112016003660T5 (en) | 2015-08-10 | 2018-05-09 | Life Technologies Corporation | Preparation of biological sample for testing |
US20230417637A1 (en) * | 2020-11-10 | 2023-12-28 | George Mason Research Foundation, Inc. | Uv coatings and dyes for laser capture microdissection |
Citations (97)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3939019A (en) * | 1974-08-02 | 1976-02-17 | Pickett John E P | Covering apparatus and method for film mounted serial tissue sections |
US4080476A (en) * | 1976-11-15 | 1978-03-21 | Datascope Corporation | Anti-fog coated optical substrates |
US4149803A (en) * | 1975-05-23 | 1979-04-17 | Litz Per Erik | Composite petrographic thin section slide and method of making same |
US4205059A (en) * | 1977-03-09 | 1980-05-27 | Hagens Gunther Von | Animal and vegetal tissues permanently preserved by synthetic resin impregnation |
US4210384A (en) * | 1976-09-11 | 1980-07-01 | Carl Zeiss-Stiftung | Inverted-design optical microscope |
US4245003A (en) * | 1979-08-17 | 1981-01-13 | James River Graphics, Inc. | Coated transparent film for laser imaging |
US4320157A (en) * | 1980-08-08 | 1982-03-16 | Hagens Gunther Von | Method for preserving large sections of biological tissue with polymers |
US4333983A (en) * | 1980-04-25 | 1982-06-08 | Optical Coating Laboratory, Inc. | Optical article and method |
US4436385A (en) * | 1980-07-25 | 1984-03-13 | Carl-Zeiss-Stiftung | Specimen holder for inverted microscopes |
US4497792A (en) * | 1981-12-18 | 1985-02-05 | Sherwood Medical Company | Specimen embedding composition |
US4508435A (en) * | 1982-06-18 | 1985-04-02 | Coulter Electronics, Inc. | Air vacuum chuck for a microscope |
US4509834A (en) * | 1982-03-24 | 1985-04-09 | Hodgson R W | Positioning apparatus for positioning a workpiece relative to a frame of reference |
US4588674A (en) * | 1982-10-14 | 1986-05-13 | Stewart Malcolm J | Laser imaging materials comprising carbon black in overlayer |
US4588579A (en) * | 1982-10-19 | 1986-05-13 | Rolf Bachhuber | Process for the production of thin sections of biological tissue |
US4600282A (en) * | 1983-11-14 | 1986-07-15 | Canon Kabushiki Kaisha | Alignment apparatus |
US4673261A (en) * | 1985-05-16 | 1987-06-16 | Alessi Industries, Inc. | Motion control apparatus for precise repeatable positioning |
US4731530A (en) * | 1986-04-21 | 1988-03-15 | Mikan Peter J | Joystick control having optical sensors |
US4743463A (en) * | 1986-02-21 | 1988-05-10 | Eastman Kodak Company | Method for forming patterns on a substrate or support |
US4752455A (en) * | 1986-05-27 | 1988-06-21 | Kms Fusion, Inc. | Pulsed laser microfabrication |
US4756922A (en) * | 1986-05-12 | 1988-07-12 | Freund Industrial Co., Ltd. | Powder coating method |
US4807984A (en) * | 1986-02-18 | 1989-02-28 | Hitachi, Ltd. | Apparatus and method for specimen inspection |
US4824229A (en) * | 1986-04-09 | 1989-04-25 | Sapporo Breweries, Ltd. | Microscope with automatic sweeping device |
US4836667A (en) * | 1986-05-06 | 1989-06-06 | Slidex Corporation | Microscope |
US4839194A (en) * | 1985-07-05 | 1989-06-13 | Bone Diagnostic Center | Methods of preparing tissue samples |
US4895735A (en) * | 1988-03-01 | 1990-01-23 | Texas Instruments Incorporated | Radiation induced pattern deposition |
US4901738A (en) * | 1987-03-31 | 1990-02-20 | Minnesota Mining And Manufacturing Company | Laser shield |
US4906494A (en) * | 1985-10-09 | 1990-03-06 | The Dow Chemical Company | Antistatic sheet material, package and method of making |
US4911782A (en) * | 1988-03-28 | 1990-03-27 | Cyto-Fluidics, Inc. | Method for forming a miniaturized biological assembly |
US4920053A (en) * | 1984-03-29 | 1990-04-24 | Olympus Optical Co., Ltd. | Method for micromanipulating cells by moving cell-containing vessel on stage of inverted microscope while pricking cells with tip of stylus |
US4923294A (en) * | 1988-10-20 | 1990-05-08 | Micron Technology, Inc. | Lead frame holding device |
US4987006A (en) * | 1990-03-26 | 1991-01-22 | Amp Incorporated | Laser transfer deposition |
US4992660A (en) * | 1989-06-26 | 1991-02-12 | Jeol Ltd. | Scanning tunneling microscope |
US5017428A (en) * | 1987-02-07 | 1991-05-21 | Pelikan Aktiengesellschaft | Multiple impression thermal transfer ribbon |
US5023187A (en) * | 1985-09-13 | 1991-06-11 | Fisher Scientific Company | Method and device for accelerated treatment of thin sample on surface |
US5029791A (en) * | 1990-03-08 | 1991-07-09 | Candela Laser Corporation | Optics X-Y positioner |
US5084356A (en) * | 1990-04-20 | 1992-01-28 | E. I. Du Pont De Nemours And Company | Film coated with glass barrier layer with metal dopant |
US5103338A (en) * | 1990-10-04 | 1992-04-07 | Crowley Kevin D | Apparatus for positioning objects for microscopic examination |
US5126877A (en) * | 1990-09-08 | 1992-06-30 | Carl-Zeiss-Stiftung | Illumination system for a surgical microscope |
US5192503A (en) * | 1990-05-23 | 1993-03-09 | Mcgrath Charles M | Probe clip in situ assay apparatus |
US5198284A (en) * | 1990-04-03 | 1993-03-30 | Konica Corporation | Thermal transfer recording medium |
US5202230A (en) * | 1990-09-07 | 1993-04-13 | Kamentsky Louis A | Methods of detecting cut cells in a tissue section |
US5217768A (en) * | 1991-09-05 | 1993-06-08 | Advanced Dielectric Technologies | Adhesiveless susceptor films and packaging structures |
US5221698A (en) * | 1991-06-27 | 1993-06-22 | The Regents Of The University Of Michigan | Bioactive composition |
US5280384A (en) * | 1988-11-09 | 1994-01-18 | Senko Medical Instrument Mfg. Co., Ltd. | Semitransparent slide, and filter combination for a microscope |
US5288996A (en) * | 1990-11-19 | 1994-02-22 | At&T Bell Laboratories | Near-field optical microscopic examination of genetic material |
US5292559A (en) * | 1992-01-10 | 1994-03-08 | Amp Incorporated | Laser transfer process |
US5296291A (en) * | 1989-05-05 | 1994-03-22 | W. R. Grace & Co.-Conn. | Heat resistant breathable films |
US5296963A (en) * | 1991-02-27 | 1994-03-22 | Hitachi, Ltd. | Apparatus and method for applying a laser beam through a microscope |
US5298963A (en) * | 1992-02-26 | 1994-03-29 | Mitsui Mining & Smelting Co., Ltd. | Apparatus for inspecting the surface of materials |
US5300540A (en) * | 1990-09-04 | 1994-04-05 | Masters Thomas R | Preserved cellular structures |
US5312393A (en) * | 1992-12-31 | 1994-05-17 | Douglas Mastel | Ring lighting system for microsurgery |
US5323009A (en) * | 1990-04-06 | 1994-06-21 | Harris Martin R | Conforcal microscope |
US5378675A (en) * | 1991-11-05 | 1995-01-03 | Konica Corporation | Thermal transfer recording image receiving sheet |
US5386112A (en) * | 1990-06-29 | 1995-01-31 | Dixon; Arthur E. | Apparatus and method for transmitted-light and reflected-light imaging |
US5391329A (en) * | 1993-08-23 | 1995-02-21 | Hughes Aircraft Company | Process for making a solid optical limiter containing a graded distribution of reverse saturable material |
US5393647A (en) * | 1993-07-16 | 1995-02-28 | Armand P. Neukermans | Method of making superhard tips for micro-probe microscopy and field emission |
US5403970A (en) * | 1989-11-21 | 1995-04-04 | Yamaha Corporation | Electrical musical instrument using a joystick-type control apparatus |
US5412503A (en) * | 1992-08-27 | 1995-05-02 | U.S. Philips Corporation | Specimen holder for a particle beam optical apparatus |
US5416131A (en) * | 1992-06-10 | 1995-05-16 | Uno Plast A/S | Article with a coating having friction-reducing properties in wet condition as well as a method for the production of such a coated article |
US5420716A (en) * | 1992-07-01 | 1995-05-30 | Olympus Optical Co., Ltd. | Surgical microscope apparatus |
US5486335A (en) * | 1992-05-01 | 1996-01-23 | Trustees Of The University Of Pennsylvania | Analysis based on flow restriction |
US5492837A (en) * | 1993-08-27 | 1996-02-20 | Biogenex Laboratories | Mounting medium for microscope slide preparations |
US5492861A (en) * | 1992-09-03 | 1996-02-20 | Deutsche Forschungsanstalt Fuer Luft-Und Raumfahrt E.V. | Process for applying structured layers using laser transfer |
US5494646A (en) * | 1993-04-14 | 1996-02-27 | Seymour; Eugene H. | Sampling device and sample adequacy system |
US5493861A (en) * | 1991-08-19 | 1996-02-27 | Danfoss A/S | Hydraulic system with pump and load |
US5504366A (en) * | 1992-07-17 | 1996-04-02 | Biotechnology Research And Development Corp. | System for analyzing surfaces of samples |
US5506725A (en) * | 1994-12-28 | 1996-04-09 | Koike Seiki Co., Ltd. | Transmission type confocal laser microscope |
US5510615A (en) * | 1994-07-12 | 1996-04-23 | Topometrix Corporation | Scanning probe microscope apparatus for use in a scanning electron microscope |
US5513768A (en) * | 1992-07-20 | 1996-05-07 | Smith; James C. | Sealing cap for containers |
US5517353A (en) * | 1993-05-28 | 1996-05-14 | Nikon Corporation | Illuminating apparatus for a microscope |
US5529841A (en) * | 1994-09-29 | 1996-06-25 | The United States Of America As Represented By The Secretary Of The Navy | Hydrogen sulfide analyzer with protective barrier |
US5598888A (en) * | 1994-09-23 | 1997-02-04 | Grumman Aerospace Corporation | Cryogenic temperature gradient microscopy chamber |
US5602674A (en) * | 1993-07-09 | 1997-02-11 | Compucyte Corp. | Computerized specimen encoder |
US5621207A (en) * | 1994-08-29 | 1997-04-15 | Hasbro, Inc. | Optical joystick using a plurality of multiplexed photoemitters and a corresponding photodetector |
US5621619A (en) * | 1990-10-25 | 1997-04-15 | Cts Corporation | All ceramic surface mount sip and dip networks having spacers and solder barriers |
US5631734A (en) * | 1994-02-10 | 1997-05-20 | Affymetrix, Inc. | Method and apparatus for detection of fluorescently labeled materials |
US5633535A (en) * | 1995-01-27 | 1997-05-27 | Chao; Clinton C. | Spacing control in electronic device assemblies |
US5638206A (en) * | 1993-09-29 | 1997-06-10 | Ushiodenki Kabushiki Kaisha | Confocal optical microscope and length measuring device using this microscope |
US5639428A (en) * | 1994-07-19 | 1997-06-17 | Becton Dickinson And Company | Method and apparatus for fully automated nucleic acid amplification, nucleic acid assay and immunoassay |
US5641896A (en) * | 1994-05-11 | 1997-06-24 | Dr. Khaled Karrai Und Dr. Miles Haines Gesellschaft Burgerlichen Rechts | Coupled oscillator scanning imager |
US5707801A (en) * | 1988-08-31 | 1998-01-13 | Aprogenex, Inc. | Manual in situ hybridization assay |
US5723290A (en) * | 1994-11-03 | 1998-03-03 | Trustees Of The University Of Pennsylvania | Methods for profiling mRNA expression in neurites |
US5728527A (en) * | 1993-07-20 | 1998-03-17 | University Of Massachusetts Medical Center | Detection of hybridized oligonocleotide probes in living cells |
US5743657A (en) * | 1994-08-06 | 1998-04-28 | The Glacier Metal Company Limited | Tilting pad journal bearing |
US5743644A (en) * | 1995-05-31 | 1998-04-28 | Anritsu Meter Co., Ltd. | Temperature measuring apparatus |
US5751839A (en) * | 1994-11-17 | 1998-05-12 | Chemunex | Apparatus and process for the detection and counting of rarely occurring mammalian cells |
US5756049A (en) * | 1996-10-25 | 1998-05-26 | Hach Company | Water testing capsule using water soluble film membranes |
US5759781A (en) * | 1995-12-22 | 1998-06-02 | Yale University | Multiparametric fluorescence in situ hybridization |
US5763191A (en) * | 1990-12-12 | 1998-06-09 | Boehringer Mannheim Gmbh | Universal binding film |
US5859699A (en) * | 1997-02-07 | 1999-01-12 | Arcturus Engineering, Inc. | Laser capture microdissection analysis vessel |
US5860937A (en) * | 1997-04-30 | 1999-01-19 | Becton, Dickinson & Company | Evacuated sample collection tube with aqueous additive |
US5912134A (en) * | 1994-09-02 | 1999-06-15 | Biometric Imaging, Inc. | Disposable cartridge and method for an assay of a biological sample |
US6010888A (en) * | 1994-03-01 | 2000-01-04 | The United States Of America As Represented By The Department Of Health And Human Services | Isolation of cellular material under microscopic visualization |
US6184973B1 (en) * | 1997-02-07 | 2001-02-06 | Arcturus Engineering, Inc. | Laser capture microdissection pressure plate and transfer arm |
US6201030B1 (en) * | 1999-09-22 | 2001-03-13 | Syntroleum Corporation | Process and apparatus for regenerating a particulate catalyst |
US6251516B1 (en) * | 1994-03-01 | 2001-06-26 | The United States Of America As Represented By The Department Of Health And Human Services | Isolation of cellular material under microscopic visualization |
US6251467B1 (en) * | 1994-03-01 | 2001-06-26 | The United States Of America As Represented By The Department Of Health And Human Services | Isolation of cellular material under microscopic visualization |
Family Cites Families (95)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2801568A (en) | 1954-11-15 | 1957-08-06 | Evelyn S Dakin | Microscope slide |
DE1938943C3 (en) | 1969-07-31 | 1974-05-30 | Siemens Ag, 1000 Berlin Und 8000 Muenchen | Cover cap for a sample vessel |
US3680947A (en) | 1970-04-21 | 1972-08-01 | Western Electric Co | Microscope apparatus with movable fluid bearing object support |
US3684099A (en) | 1970-07-21 | 1972-08-15 | Carl T Kiebach | Assembly element for press |
US3705769A (en) | 1970-11-12 | 1972-12-12 | Johannsmeier Karl Heinz | Optical alignment and contact printing system with improved chuck assembly |
US3836231A (en) | 1971-09-30 | 1974-09-17 | Gen Electric | Uniform liquid crystal cells and method for making the same |
JPS526097B2 (en) | 1972-03-14 | 1977-02-18 | ||
US3853591A (en) * | 1972-07-19 | 1974-12-10 | Du Pont | Phosphate coated polymeric shaped objects |
CH566015A5 (en) | 1973-04-12 | 1975-08-29 | Ciba Geigy Ag | Producing relief contrast in microscope image of phase object - including suppression of disturbing interference and refraction |
US3848962A (en) | 1973-10-18 | 1974-11-19 | Coulter Electronics | Slide mounting apparatus for microscopy |
US4064205A (en) * | 1974-07-02 | 1977-12-20 | Logetronics, Inc. | Method for making a printing plate from a porous substrate |
DE2826363C2 (en) | 1978-06-16 | 1984-08-16 | Merck Patent Gmbh, 6100 Darmstadt | Cover sheet for use in microscopic dyeing processes and processes for their manufacture |
IT1165685B (en) | 1979-06-12 | 1987-04-22 | Agusta Aeronaut Costr | PROCEDURE AND DEVICE FOR THE ASSEMBLY OF PIECES INSIDE A ROOM UNDER VACUUM OF AN ELECTRONIC MICROSCOPE |
US4552033A (en) | 1980-07-08 | 1985-11-12 | Gebr. Marzhauser Wetzlar oHG | Drive system for a microscope stage or the like |
US4467915A (en) * | 1980-08-20 | 1984-08-28 | Snyder Robert G | Emulsion package and method of mixing the emulsion |
AU9130382A (en) | 1981-12-11 | 1983-06-16 | Sterilin Ltd. | Piercable closure |
JPS58212944A (en) * | 1982-06-07 | 1983-12-10 | 出光石油化学株式会社 | Laminate |
US4538885A (en) | 1982-06-18 | 1985-09-03 | Coulter Electronics, Inc. | Optical microscope system |
US4624915A (en) | 1982-07-29 | 1986-11-25 | Board Of Trustees Of Michigan State University | Positive selection sorting of cells |
US4629687A (en) | 1982-07-29 | 1986-12-16 | Board Of Trustees Of Michigan State University | Positive selection sorting of cells |
EP0116953A2 (en) | 1983-02-18 | 1984-08-29 | Hitachi, Ltd. | Alignment apparatus |
US4627009A (en) | 1983-05-24 | 1986-12-02 | Nanometrics Inc. | Microscope stage assembly and control system |
DE3319564A1 (en) | 1983-05-30 | 1984-12-06 | Arthur Pfeiffer Vakuumtechnik Wetzlar Gmbh, 6334 Asslar | METHOD FOR PRODUCING FLEXIBLE, SUSTAINABLY MADE NON-PRESERVED AND PRESERVED BIOLOGICAL MATERIALS |
US4684781A (en) * | 1985-01-29 | 1987-08-04 | Physical Sciences, Inc. | Method for bonding using laser induced heat and pressure |
DE3508094A1 (en) | 1985-03-07 | 1986-09-11 | Fa. Carl Zeiss, 7920 Heidenheim | CROSS TABLE FOR MICROSCOPE |
US5281517A (en) | 1985-11-04 | 1994-01-25 | Cell Analysis Systems, Inc. | Methods for immunoploidy analysis |
US4836194A (en) | 1986-08-29 | 1989-06-06 | Safeguard Industrial Corporation | Therapeutic lumbosacral appliance |
JPH07122694B2 (en) | 1986-10-16 | 1995-12-25 | オリンパス光学工業株式会社 | Illumination device for microscope |
JPH0757226B2 (en) | 1986-10-27 | 1995-06-21 | オリンパス光学工業株式会社 | Surgical microscope |
US4856873A (en) | 1987-05-15 | 1989-08-15 | Storz Instrument Company | Documentation illumination module |
US5089909A (en) | 1987-05-15 | 1992-02-18 | Storz Instrument Company | Documentation illumination module for a microscope system |
US5143552A (en) | 1988-03-09 | 1992-09-01 | Tokyo Electron Limited | Coating equipment |
US5225326A (en) | 1988-08-31 | 1993-07-06 | Research Development Foundation | One step in situ hybridization assay |
US5253110A (en) | 1988-12-22 | 1993-10-12 | Nikon Corporation | Illumination optical arrangement |
US5037613A (en) | 1989-03-16 | 1991-08-06 | Eastman Kodak Company | Incubator |
US4954715A (en) | 1989-06-26 | 1990-09-04 | Zoeld Tibor | Method and apparatus for an optimized multiparameter flow-through particle and cell analyzer |
US4964708A (en) | 1989-07-14 | 1990-10-23 | Mason Michael S | Microscope for medical surgery |
IN172390B (en) | 1989-07-18 | 1993-07-10 | Ethicon Inc | |
GB8918888D0 (en) | 1989-08-18 | 1989-09-27 | Lrc Products | Production of thin walled hollow polymeric articles and polymeric coatings on substrates |
US5057689A (en) | 1989-09-20 | 1991-10-15 | Matsushita Electric Industrial Co., Ltd. | Scanning electron microscope and a method of displaying cross sectional profiles using the same |
WO1991012187A1 (en) * | 1990-02-06 | 1991-08-22 | Sumitomo Bakelite Company Limited | Covering tape for electronic component chip |
TW199858B (en) | 1990-03-30 | 1993-02-11 | Fujirebio Kk | |
US5077620A (en) | 1990-06-06 | 1991-12-31 | George Mauro | Motorized optical component positioning stage |
US5096775A (en) * | 1990-09-05 | 1992-03-17 | Mitsubishi Petrochemical Co., Ltd. | Resin laminate |
DE9013260U1 (en) | 1990-09-19 | 1990-11-22 | Fa. Carl Zeiss, 7920 Heidenheim, De | |
DE4029638A1 (en) | 1990-09-19 | 1992-03-26 | Zeiss Carl Fa | SWIVELING DEVICE FOR CARRIER DEVICES FOR OPTICAL OBSERVATION DEVICES |
US5665582A (en) | 1990-10-29 | 1997-09-09 | Dekalb Genetics Corp. | Isolation of biological materials |
US5367401A (en) | 1990-11-23 | 1994-11-22 | Perceptive Scientific Instruments, Inc. | Microscope slide rotary stage |
US5165297A (en) | 1991-02-15 | 1992-11-24 | Albert Einstein College Of Medicine Of Yeshiva University, A Div. Of Yeshiva Univ. | Remote controlled micromanipulator |
JP2559730Y2 (en) | 1991-02-20 | 1998-01-19 | オリンパス光学工業株式会社 | Moving stage |
US5817462A (en) | 1995-02-21 | 1998-10-06 | Applied Spectral Imaging | Method for simultaneous detection of multiple fluorophores for in situ hybridization and multicolor chromosome painting and banding |
US5345333A (en) | 1991-04-19 | 1994-09-06 | Unimat (Usa) Corporation | Illumination system and method for a high definition light microscope |
US5262891A (en) | 1991-04-30 | 1993-11-16 | Olympus Optical Co., Ltd. | Optical microscope of the transmission type |
US5162941A (en) | 1991-07-23 | 1992-11-10 | The Board Of Governors Of Wayne State University | Confocal microscope |
US5434703A (en) | 1991-10-09 | 1995-07-18 | Fuji Photo Optical Co., Ltd. | Binocular stereomicroscope |
DE4134481C2 (en) | 1991-10-18 | 1998-04-09 | Zeiss Carl Fa | Surgical microscope for computer-aided, stereotactic microsurgery |
JP3067331B2 (en) | 1991-10-30 | 2000-07-17 | 株式会社ニコン | microscope |
IL103674A0 (en) | 1991-11-19 | 1993-04-04 | Houston Advanced Res Center | Method and apparatus for molecule detection |
DE4139664A1 (en) | 1991-12-02 | 1993-06-03 | Diagen Inst Molekularbio | DEVICE AND METHOD FOR ISOLATING AND CLEANING NUCLEIC ACIDS |
US5317058A (en) | 1992-04-17 | 1994-05-31 | Hughes Aircraft Company | Microwave-absorbing materials containing polar icosahedral molecular units and methods of making the same |
JP3362892B2 (en) | 1992-04-28 | 2003-01-07 | オリンパス光学工業株式会社 | microscope |
AU4402793A (en) | 1992-05-29 | 1993-12-30 | Regents Of The University Of California, The | Coated transplant and method for making same |
US5535052A (en) | 1992-07-24 | 1996-07-09 | Carl-Zeiss-Stiftung | Laser microscope |
DE4225962A1 (en) * | 1992-08-06 | 1994-02-10 | Hoechst Ag | Layer element and method of its production |
AT403096B (en) | 1992-09-08 | 1997-11-25 | Sitte Hellmuth | METHOD AND DEVICE FOR PREPARING MICROSCOPIC, IN PARTICULAR ELECTRON MICROSCOPIC PREPARATIONS FOR THE CUT PREPARATION |
US5349436A (en) | 1992-12-02 | 1994-09-20 | Harry Fisch | Biological assembly |
US5357366A (en) | 1992-12-08 | 1994-10-18 | Marchlenski Stanley P | Mechanical stage adjustment mechanism |
US5337178A (en) | 1992-12-23 | 1994-08-09 | International Business Machines Corporation | Titlable optical microscope stage |
US5479252A (en) | 1993-06-17 | 1995-12-26 | Ultrapointe Corporation | Laser imaging system for inspection and analysis of sub-micron particles |
US5537863A (en) | 1993-07-15 | 1996-07-23 | Nikon Corporation | Scanning probe microscope having a cantilever used therein |
US5532873A (en) | 1993-09-08 | 1996-07-02 | Dixon; Arthur E. | Scanning beam laser microscope with wide range of magnification |
US5576264A (en) * | 1993-11-24 | 1996-11-19 | Dai Nippon Printing Co., Ltd. | Receiving-layer transfer sheet |
US5578832A (en) | 1994-09-02 | 1996-11-26 | Affymetrix, Inc. | Method and apparatus for imaging a sample on a device |
US5843644A (en) | 1994-03-01 | 1998-12-01 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Isolation of cellular material under microscopic visualization using an adhesive/extraction reagent tipped probe |
US5557456A (en) | 1994-03-04 | 1996-09-17 | Oncometrics Imaging Corp. | Personal interface device for positioning of a microscope stage |
JPH07290824A (en) * | 1994-04-22 | 1995-11-07 | Pilot Ink Co Ltd | Thermally discoloring laminate |
US5468967A (en) | 1994-08-26 | 1995-11-21 | National University Of Singapore | Double reflection cathodoluminescence detector with extremely high discrimination against backscattered electrons |
US5559329A (en) | 1994-08-31 | 1996-09-24 | Touchstone Research Laboratory, Ltd. | Scanning electron microscope fiber push-out apparatus and method |
US5471260A (en) | 1994-10-28 | 1995-11-28 | Leica Inc. | Joystick for an ophthalmic instrument where vertical movement is controlled by rotating the joystick |
US5587748A (en) | 1994-10-28 | 1996-12-24 | Leica Inc. | Joystick override control for an ophthalmic instrument |
US5556790A (en) | 1994-12-05 | 1996-09-17 | Pettit; John W. | Method for Automated DNA sequencing |
US5532476A (en) | 1994-12-21 | 1996-07-02 | Mikan; Peter J. | Redundant indicator for detecting neutral position of joystick member |
US5536941A (en) | 1995-02-22 | 1996-07-16 | Gatan, Inc. | Rotatable wide angle camera and prism assembly for electron microscopes |
US5558329A (en) | 1995-03-01 | 1996-09-24 | Liu; William S. Y. | Photoelectric digitized joystick |
MX9700732A (en) * | 1995-06-07 | 1997-08-30 | Becton Dickinson Co | Method and apparatus for generating alerts. |
US5659421A (en) | 1995-07-05 | 1997-08-19 | Neuromedical Systems, Inc. | Slide positioning and holding device |
DE19603996C2 (en) | 1996-02-05 | 2002-08-29 | P A L M Gmbh Mikrolaser Techno | Sorting process for planar biological objects with laser beams |
WO1997029354A1 (en) | 1996-02-05 | 1997-08-14 | Bayer Aktiengesellschaft | Process and device for sorting and for extraction of biological objects arranged on planar means, such as biological cells or cell organelles, histological sections, chromosome particles etc. using laser beams |
US5674328A (en) * | 1996-04-26 | 1997-10-07 | General Electric Company | Dry tape covered laser shock peening |
US5786022A (en) | 1996-10-31 | 1998-07-28 | Ethicon, Inc. | Coating mixture for surgical articles |
US6100051A (en) | 1997-06-27 | 2000-08-08 | The United States Of America As Represented By The Department Of Health And Human Services | Method utilizing convex geometry for laser capture microdissection |
US5812312A (en) | 1997-09-04 | 1998-09-22 | Lorincz; Andrew Endre | Microscope slide |
US5985085A (en) * | 1997-10-01 | 1999-11-16 | Arcturus Engineering, Inc. | Method of manufacturing consumable for laser capture microdissection |
US6251216B1 (en) * | 1997-12-17 | 2001-06-26 | Matsushita Electronics Corporation | Apparatus and method for plasma processing |
US5972667A (en) * | 1998-05-19 | 1999-10-26 | Cell Robotics, Inc. | Method and apparatus for activating a thermo-enzyme reaction with electromagnetic energy |
-
1997
- 1997-02-14 US US08/800,882 patent/US6495195B2/en not_active Expired - Lifetime
-
1998
- 1998-01-29 WO PCT/US1998/001634 patent/WO1998036261A1/en active Search and Examination
- 1998-01-29 AU AU61365/98A patent/AU6136598A/en not_active Abandoned
-
2002
- 2002-10-03 US US10/264,420 patent/US20030031781A1/en not_active Abandoned
Patent Citations (99)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3939019A (en) * | 1974-08-02 | 1976-02-17 | Pickett John E P | Covering apparatus and method for film mounted serial tissue sections |
US4149803A (en) * | 1975-05-23 | 1979-04-17 | Litz Per Erik | Composite petrographic thin section slide and method of making same |
US4210384A (en) * | 1976-09-11 | 1980-07-01 | Carl Zeiss-Stiftung | Inverted-design optical microscope |
US4080476A (en) * | 1976-11-15 | 1978-03-21 | Datascope Corporation | Anti-fog coated optical substrates |
US4205059A (en) * | 1977-03-09 | 1980-05-27 | Hagens Gunther Von | Animal and vegetal tissues permanently preserved by synthetic resin impregnation |
US4245003A (en) * | 1979-08-17 | 1981-01-13 | James River Graphics, Inc. | Coated transparent film for laser imaging |
US4333983A (en) * | 1980-04-25 | 1982-06-08 | Optical Coating Laboratory, Inc. | Optical article and method |
US4436385A (en) * | 1980-07-25 | 1984-03-13 | Carl-Zeiss-Stiftung | Specimen holder for inverted microscopes |
US4320157A (en) * | 1980-08-08 | 1982-03-16 | Hagens Gunther Von | Method for preserving large sections of biological tissue with polymers |
US4497792A (en) * | 1981-12-18 | 1985-02-05 | Sherwood Medical Company | Specimen embedding composition |
US4509834A (en) * | 1982-03-24 | 1985-04-09 | Hodgson R W | Positioning apparatus for positioning a workpiece relative to a frame of reference |
US4508435A (en) * | 1982-06-18 | 1985-04-02 | Coulter Electronics, Inc. | Air vacuum chuck for a microscope |
US4588674A (en) * | 1982-10-14 | 1986-05-13 | Stewart Malcolm J | Laser imaging materials comprising carbon black in overlayer |
US4588579A (en) * | 1982-10-19 | 1986-05-13 | Rolf Bachhuber | Process for the production of thin sections of biological tissue |
US4600282A (en) * | 1983-11-14 | 1986-07-15 | Canon Kabushiki Kaisha | Alignment apparatus |
US4920053A (en) * | 1984-03-29 | 1990-04-24 | Olympus Optical Co., Ltd. | Method for micromanipulating cells by moving cell-containing vessel on stage of inverted microscope while pricking cells with tip of stylus |
US4673261A (en) * | 1985-05-16 | 1987-06-16 | Alessi Industries, Inc. | Motion control apparatus for precise repeatable positioning |
US4839194A (en) * | 1985-07-05 | 1989-06-13 | Bone Diagnostic Center | Methods of preparing tissue samples |
US5023187A (en) * | 1985-09-13 | 1991-06-11 | Fisher Scientific Company | Method and device for accelerated treatment of thin sample on surface |
US4906494A (en) * | 1985-10-09 | 1990-03-06 | The Dow Chemical Company | Antistatic sheet material, package and method of making |
US4807984A (en) * | 1986-02-18 | 1989-02-28 | Hitachi, Ltd. | Apparatus and method for specimen inspection |
US4743463A (en) * | 1986-02-21 | 1988-05-10 | Eastman Kodak Company | Method for forming patterns on a substrate or support |
US4824229A (en) * | 1986-04-09 | 1989-04-25 | Sapporo Breweries, Ltd. | Microscope with automatic sweeping device |
US4731530A (en) * | 1986-04-21 | 1988-03-15 | Mikan Peter J | Joystick control having optical sensors |
US4836667A (en) * | 1986-05-06 | 1989-06-06 | Slidex Corporation | Microscope |
US4756922A (en) * | 1986-05-12 | 1988-07-12 | Freund Industrial Co., Ltd. | Powder coating method |
US4752455A (en) * | 1986-05-27 | 1988-06-21 | Kms Fusion, Inc. | Pulsed laser microfabrication |
US5017428A (en) * | 1987-02-07 | 1991-05-21 | Pelikan Aktiengesellschaft | Multiple impression thermal transfer ribbon |
US4901738A (en) * | 1987-03-31 | 1990-02-20 | Minnesota Mining And Manufacturing Company | Laser shield |
US4895735A (en) * | 1988-03-01 | 1990-01-23 | Texas Instruments Incorporated | Radiation induced pattern deposition |
US4911782A (en) * | 1988-03-28 | 1990-03-27 | Cyto-Fluidics, Inc. | Method for forming a miniaturized biological assembly |
US5707801A (en) * | 1988-08-31 | 1998-01-13 | Aprogenex, Inc. | Manual in situ hybridization assay |
US4923294A (en) * | 1988-10-20 | 1990-05-08 | Micron Technology, Inc. | Lead frame holding device |
US5280384A (en) * | 1988-11-09 | 1994-01-18 | Senko Medical Instrument Mfg. Co., Ltd. | Semitransparent slide, and filter combination for a microscope |
US5296291A (en) * | 1989-05-05 | 1994-03-22 | W. R. Grace & Co.-Conn. | Heat resistant breathable films |
US4992660A (en) * | 1989-06-26 | 1991-02-12 | Jeol Ltd. | Scanning tunneling microscope |
US5403970A (en) * | 1989-11-21 | 1995-04-04 | Yamaha Corporation | Electrical musical instrument using a joystick-type control apparatus |
US5029791A (en) * | 1990-03-08 | 1991-07-09 | Candela Laser Corporation | Optics X-Y positioner |
US4987006A (en) * | 1990-03-26 | 1991-01-22 | Amp Incorporated | Laser transfer deposition |
US5198284A (en) * | 1990-04-03 | 1993-03-30 | Konica Corporation | Thermal transfer recording medium |
US5323009A (en) * | 1990-04-06 | 1994-06-21 | Harris Martin R | Conforcal microscope |
US5084356A (en) * | 1990-04-20 | 1992-01-28 | E. I. Du Pont De Nemours And Company | Film coated with glass barrier layer with metal dopant |
US5192503A (en) * | 1990-05-23 | 1993-03-09 | Mcgrath Charles M | Probe clip in situ assay apparatus |
US5386112A (en) * | 1990-06-29 | 1995-01-31 | Dixon; Arthur E. | Apparatus and method for transmitted-light and reflected-light imaging |
US5300540A (en) * | 1990-09-04 | 1994-04-05 | Masters Thomas R | Preserved cellular structures |
US5202230A (en) * | 1990-09-07 | 1993-04-13 | Kamentsky Louis A | Methods of detecting cut cells in a tissue section |
US5126877A (en) * | 1990-09-08 | 1992-06-30 | Carl-Zeiss-Stiftung | Illumination system for a surgical microscope |
US5103338A (en) * | 1990-10-04 | 1992-04-07 | Crowley Kevin D | Apparatus for positioning objects for microscopic examination |
US5621619A (en) * | 1990-10-25 | 1997-04-15 | Cts Corporation | All ceramic surface mount sip and dip networks having spacers and solder barriers |
US5288996A (en) * | 1990-11-19 | 1994-02-22 | At&T Bell Laboratories | Near-field optical microscopic examination of genetic material |
US5763191A (en) * | 1990-12-12 | 1998-06-09 | Boehringer Mannheim Gmbh | Universal binding film |
US5296963A (en) * | 1991-02-27 | 1994-03-22 | Hitachi, Ltd. | Apparatus and method for applying a laser beam through a microscope |
US5221698A (en) * | 1991-06-27 | 1993-06-22 | The Regents Of The University Of Michigan | Bioactive composition |
US5493861A (en) * | 1991-08-19 | 1996-02-27 | Danfoss A/S | Hydraulic system with pump and load |
US5217768A (en) * | 1991-09-05 | 1993-06-08 | Advanced Dielectric Technologies | Adhesiveless susceptor films and packaging structures |
US5378675A (en) * | 1991-11-05 | 1995-01-03 | Konica Corporation | Thermal transfer recording image receiving sheet |
US5292559A (en) * | 1992-01-10 | 1994-03-08 | Amp Incorporated | Laser transfer process |
US5298963A (en) * | 1992-02-26 | 1994-03-29 | Mitsui Mining & Smelting Co., Ltd. | Apparatus for inspecting the surface of materials |
US5486335A (en) * | 1992-05-01 | 1996-01-23 | Trustees Of The University Of Pennsylvania | Analysis based on flow restriction |
US5416131A (en) * | 1992-06-10 | 1995-05-16 | Uno Plast A/S | Article with a coating having friction-reducing properties in wet condition as well as a method for the production of such a coated article |
US5420716A (en) * | 1992-07-01 | 1995-05-30 | Olympus Optical Co., Ltd. | Surgical microscope apparatus |
US5619035A (en) * | 1992-07-17 | 1997-04-08 | Biotechnology Research & Development Corporation | System for analyzing surfaces of samples |
US5504366A (en) * | 1992-07-17 | 1996-04-02 | Biotechnology Research And Development Corp. | System for analyzing surfaces of samples |
US5513768A (en) * | 1992-07-20 | 1996-05-07 | Smith; James C. | Sealing cap for containers |
US5412503A (en) * | 1992-08-27 | 1995-05-02 | U.S. Philips Corporation | Specimen holder for a particle beam optical apparatus |
US5492861A (en) * | 1992-09-03 | 1996-02-20 | Deutsche Forschungsanstalt Fuer Luft-Und Raumfahrt E.V. | Process for applying structured layers using laser transfer |
US5312393A (en) * | 1992-12-31 | 1994-05-17 | Douglas Mastel | Ring lighting system for microsurgery |
US5494646A (en) * | 1993-04-14 | 1996-02-27 | Seymour; Eugene H. | Sampling device and sample adequacy system |
US5517353A (en) * | 1993-05-28 | 1996-05-14 | Nikon Corporation | Illuminating apparatus for a microscope |
US5602674A (en) * | 1993-07-09 | 1997-02-11 | Compucyte Corp. | Computerized specimen encoder |
US5393647A (en) * | 1993-07-16 | 1995-02-28 | Armand P. Neukermans | Method of making superhard tips for micro-probe microscopy and field emission |
US5728527A (en) * | 1993-07-20 | 1998-03-17 | University Of Massachusetts Medical Center | Detection of hybridized oligonocleotide probes in living cells |
US5391329A (en) * | 1993-08-23 | 1995-02-21 | Hughes Aircraft Company | Process for making a solid optical limiter containing a graded distribution of reverse saturable material |
US5492837A (en) * | 1993-08-27 | 1996-02-20 | Biogenex Laboratories | Mounting medium for microscope slide preparations |
US5638206A (en) * | 1993-09-29 | 1997-06-10 | Ushiodenki Kabushiki Kaisha | Confocal optical microscope and length measuring device using this microscope |
US5631734A (en) * | 1994-02-10 | 1997-05-20 | Affymetrix, Inc. | Method and apparatus for detection of fluorescently labeled materials |
US6010888A (en) * | 1994-03-01 | 2000-01-04 | The United States Of America As Represented By The Department Of Health And Human Services | Isolation of cellular material under microscopic visualization |
US6251516B1 (en) * | 1994-03-01 | 2001-06-26 | The United States Of America As Represented By The Department Of Health And Human Services | Isolation of cellular material under microscopic visualization |
US6251467B1 (en) * | 1994-03-01 | 2001-06-26 | The United States Of America As Represented By The Department Of Health And Human Services | Isolation of cellular material under microscopic visualization |
US5641896A (en) * | 1994-05-11 | 1997-06-24 | Dr. Khaled Karrai Und Dr. Miles Haines Gesellschaft Burgerlichen Rechts | Coupled oscillator scanning imager |
US5510615A (en) * | 1994-07-12 | 1996-04-23 | Topometrix Corporation | Scanning probe microscope apparatus for use in a scanning electron microscope |
US5639428A (en) * | 1994-07-19 | 1997-06-17 | Becton Dickinson And Company | Method and apparatus for fully automated nucleic acid amplification, nucleic acid assay and immunoassay |
US5743657A (en) * | 1994-08-06 | 1998-04-28 | The Glacier Metal Company Limited | Tilting pad journal bearing |
US5621207A (en) * | 1994-08-29 | 1997-04-15 | Hasbro, Inc. | Optical joystick using a plurality of multiplexed photoemitters and a corresponding photodetector |
US5912134A (en) * | 1994-09-02 | 1999-06-15 | Biometric Imaging, Inc. | Disposable cartridge and method for an assay of a biological sample |
US5598888A (en) * | 1994-09-23 | 1997-02-04 | Grumman Aerospace Corporation | Cryogenic temperature gradient microscopy chamber |
US5529841A (en) * | 1994-09-29 | 1996-06-25 | The United States Of America As Represented By The Secretary Of The Navy | Hydrogen sulfide analyzer with protective barrier |
US5723290A (en) * | 1994-11-03 | 1998-03-03 | Trustees Of The University Of Pennsylvania | Methods for profiling mRNA expression in neurites |
US5751839A (en) * | 1994-11-17 | 1998-05-12 | Chemunex | Apparatus and process for the detection and counting of rarely occurring mammalian cells |
US5506725A (en) * | 1994-12-28 | 1996-04-09 | Koike Seiki Co., Ltd. | Transmission type confocal laser microscope |
US5633535A (en) * | 1995-01-27 | 1997-05-27 | Chao; Clinton C. | Spacing control in electronic device assemblies |
US5743644A (en) * | 1995-05-31 | 1998-04-28 | Anritsu Meter Co., Ltd. | Temperature measuring apparatus |
US5759781A (en) * | 1995-12-22 | 1998-06-02 | Yale University | Multiparametric fluorescence in situ hybridization |
US5756049A (en) * | 1996-10-25 | 1998-05-26 | Hach Company | Water testing capsule using water soluble film membranes |
US6184973B1 (en) * | 1997-02-07 | 2001-02-06 | Arcturus Engineering, Inc. | Laser capture microdissection pressure plate and transfer arm |
US6215550B1 (en) * | 1997-02-07 | 2001-04-10 | Arcturus Engineering, Inc. | Laser capture microdissection optical system |
US5859699A (en) * | 1997-02-07 | 1999-01-12 | Arcturus Engineering, Inc. | Laser capture microdissection analysis vessel |
US5860937A (en) * | 1997-04-30 | 1999-01-19 | Becton, Dickinson & Company | Evacuated sample collection tube with aqueous additive |
US6201030B1 (en) * | 1999-09-22 | 2001-03-13 | Syntroleum Corporation | Process and apparatus for regenerating a particulate catalyst |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090054264A1 (en) * | 2006-02-27 | 2009-02-26 | Commissariat A L'energie Atomique | Method of Fabricating an Array of Capillaries on a Chip |
Also Published As
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US6495195B2 (en) | 2002-12-17 |
WO1998036261A1 (en) | 1998-08-20 |
US20010003009A1 (en) | 2001-06-07 |
AU6136598A (en) | 1998-09-08 |
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