WO2006052492A1 - Preglued coverglass with roughened glue surface - Google Patents

Preglued coverglass with roughened glue surface Download PDF

Info

Publication number
WO2006052492A1
WO2006052492A1 PCT/US2005/039152 US2005039152W WO2006052492A1 WO 2006052492 A1 WO2006052492 A1 WO 2006052492A1 US 2005039152 W US2005039152 W US 2005039152W WO 2006052492 A1 WO2006052492 A1 WO 2006052492A1
Authority
WO
WIPO (PCT)
Prior art keywords
coverslip
glue
glued
roughened
glass
Prior art date
Application number
PCT/US2005/039152
Other languages
French (fr)
Inventor
Kurt Reinhardt
Miroslav Holubec
Original Assignee
Ventana Medical Systems, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ventana Medical Systems, Inc. filed Critical Ventana Medical Systems, Inc.
Publication of WO2006052492A1 publication Critical patent/WO2006052492A1/en

Links

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • GPHYSICS
    • G02OPTICS
    • G02BOPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00Microscopes
    • G02B21/34Microscope slides, e.g. mounting specimens on microscope slides
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0689Sealing
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/04Closures and closing means
    • B01L2300/041Connecting closures to device or container
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0822Slides

Definitions

  • the present invention relates generally to new and improved coverslip and more particularly to an improved stackable non-stick coverslip for use, for example, in an automated coverslipper apparatus or system.
  • a tissue specimen such as a human tissue specimen
  • the glass slide carrying the tissue section under examination, is subjected to certain reagents and stained in accordance with an established protocol in order to facilitate characterization and diagnosis of the tissue sample.
  • the glass slide is then permanently "covered” with a chemical or glass coverslip to substantially avoid contamination and to permit long-term archiving of the slide.
  • One presently available glass coverslip has the same configuration as a conventional glass slide, i.e., substantially rectangular. The length and thickness are, by comparison, significantly reduced to decrease production costs.
  • Another available glass coverslip is substantially circular, having a diameter corresponding to the width of a conventional glass slide.
  • Glass coverslips may be placed upon the tissue-carrying slide manually or by an automated coverslipper.
  • an automated system is shown in U.S. Pat. No. 3,833,449, and the teachings thereof are incorporated herein by reference.
  • the glass coverslips are vertically stacked in a housing, and an individual coverslip is placed upon the glass slide by either a piston-like mechanism (which pushes the uppermost coverslip in the housing onto the glass slide) or a vacuum mechanism (which lifts the top coverslip for appropriate placement and release).
  • Moisture between adjacent coverslips in the housing substantially interferes with the covering process and equipment. That is, condensation interposed adjacent stacked coverslips causes adherence, or "sticking," such that more than one coverslip is extracted by a single covering operation. The result is often one or more broken coverslips and a certain amount of "downtime" for maintenance of the system.
  • Glues are typically used to permanently bond the coverslip to the glass slide, over the stained tissue sample. Such a glue is usually applied manually to either the coverslip or glass slide.
  • An embodiment of the invention is directed to a pre-glued coverslip having a roughened glue surface.
  • the invention is also directed to a method of making a pre-glued coverslip comprising applying an essentially flat glue surface to a coverslip and then disrupting the essentially flat glued surface of a pre-glued coverslip thereby reducing its tendency to stick to another coverslip.
  • Another embodiment of the invention is a coverslip that has the glue spayed on in stripes thereby forming intervening channels of glue so that channels of air communicate with the edge of the coverslip.
  • Figures 1 A-IB are photographs of a pre-glued glass coverslip (IA) and a roughened pre-glued glass coverslip (IB).
  • Figure 2 is a photomicrograph of the roughened coverslip of Figure IB at 15x power, showing with more detail the scratches in the glue surface.
  • Figure 3 is a front elevational diagram of a pre-glued coverslip. Description of the Preferred Embodiments
  • the invention is an improvement upon the pre-glued coverslip described in U.S. Patent No. 6,759,011 (Richards, et. al.), hereby incorporated by reference. However, this improvement is potentially applicable to any coverslip.
  • U.S. Patent No. 6,759,011 (Richards, et. al.), hereby incorporated by reference.
  • this improvement is potentially applicable to any coverslip.
  • a pre-glued coverslip there is described a pre-glued coverslip. Coverslips are usually stored arranged in a stack and then dispensed as needed by "peeling" them apart one-at-a-time. Since they are very thin and tend to stick together, many means have been pursued in the past to counter their tendency to stick together. It has been found that elevated humidity will worsen this tendency of the glued side and the non-glued side of an adjacent coverslip to stick together. It is postulated that this may be due to Van der Vaals forces.
  • the improvement is directed to interrupting the tendency of objects in close proximity to stick together, and in one embodiment the invention is a slight roughening of the surface of the glue which results in a stick-free pre- glued coverslip. It is postulated that this roughening disrupts the Van de Vaals forces holding the closely-aligned surfaces together.
  • the prior art pre-glued coverslip in a high humidity environment, had a sticking rate in excess of 20% after 24 or more hours of exposure, hi 380 trials of the roughened coverglass, the rate has dropped to 0%.
  • the pre-glued coverslip of the 6,759,011 patent describes a coverslip having protuberances applied to one side and glue to the other.
  • the present invention is not so limited, and any pre-glued coverslip may be used. whether it has protuberances on the opposing side or not.
  • the stackable non-stick coverslip 10 has an adhesive 52 applied to a central region, generally designated 54, of the bottom surface 30B.
  • the adhesive 52 is preferably a liquid that dries, upon application to the coverslip 10, to a tackless or only slightly tacky state.
  • the adhesive 52 is activated or partially dissolved by a solvent, prior to placement onto a glass slide by applying solvent to the pre-glued coverslip surface, hi another embodiment, the solvent is applied manually, hi yet a further embodiment the adhesive maybe applied to less than the full area of the coverslip surface so that bare areas remain.
  • This application of the adhesive may result in a pattern of stripes or layers that can have the same effect as a scratched or disrupted glue surface, that is, it will have areas of coverage separated by gaps that will allow air to flow between the glued areas (an "open-access" pattern).
  • the adhesive may be applied via sprayer, mechanical applicator, or any other method for applying viscous liquids to the surface of glass.
  • the coverslip 10 is affixed or bonded to the top surface of the glass slide.
  • the glass slide can then be stored for future analysis and study or as a permanent record of the analysis preformed.
  • the adhesive 52 is preferably oil-based or water-insoluble, such that the solvent is non-aqueous, i.e., hydrophobic or lipophilic.
  • Acrylic copolymers such as Acryloid® A-21, commercially available from Rohm and Haas, Philadelphia, Pa., are suitable.
  • Other suitable adhesives include olef ⁇ n-based materials, e.g., vinyl and acrylate based polymers; cellulose acetates; cyanoacrylates; silicone-containing materials including silane- and siloxane- terminated monomer based polymers; polytetrafluoroethylene based adhesives; and hydrocarbon based polymers.
  • Suitable solvents to render the adhesive 52 tacky include aromatic hydrocarbons such as toluene, xylene, and benzene; silicones such as dimethicones, cyclomethicones and substituted siloxanes; aromatic and aliphatic hydrocarbons; alkyl esters; benzyl or alkyl benzoates; alkyl, alkoxyalkyl and glyceryl esters; and mixtures thereof. While an oil-based or water-insoluble solvent is preferred, a water- based solvent, such as Shur/Mount Liquid Mounting Medium (VWR Cat. No. 15148-062), may be utilized with certain stains.
  • aromatic hydrocarbons such as toluene, xylene, and benzene
  • silicones such as dimethicones, cyclomethicones and substituted siloxanes
  • aromatic and aliphatic hydrocarbons alkyl esters
  • benzyl or alkyl benzoates alkyl, alkoxy
  • Roughening methods might include: rubbing with sand paper, steel wool, emery board, wire brush etc.; sand or bead blasting. Applying a rough coating might be accomplished by a sputtering application, impressing a pattern before the glue is fully cured, or applying portions of the glue in more than one pass. An automated industrial process of any of the above would likely come at the glass sheet level, before any coverslips are cut.
  • the pattern need not be longitudinal scratches as we have done, but could also be transverse. Moreover, a grid or even random pattern of raised or removed material (i.e., surface disruption) would be sufficient.
  • the scratch depth need only be enough to eliminate the sticking, but not so much as to cause air bubbles to form under the coverslip with the coverslipper in operation.

Abstract

An embodiment of the invention is directed to a pre-glued coverslip (10) having a roughened glue surface (52). The invention is also directed to a method of making a pre-glued coverslip comprising applying an essentially flat glue surface to a coverslip and then disrupting the essentially flat glued surface of a pre-glued coverslip thereby reducing its tendency to stick to another coverslip. Another embodiment of the invention is a coverslip that has the glue spayed on in stripes thereby forming intervening channels of glue so that channels of air communicate with the edge of the coverslip.

Description

PREGLUED COVERGLASS WITH ROUGHENED GLUE SURFACE
Cross-reference to Related Applications
This application is a nonprovisional utility patent application claiming priority to U.S. Ser. No. 60/626340, filed November 8, 2004.
1. Field of the Invention
The present invention relates generally to new and improved coverslip and more particularly to an improved stackable non-stick coverslip for use, for example, in an automated coverslipper apparatus or system.
2. Description of Related Art
As is well known in the medical art, a tissue specimen, such as a human tissue specimen, is mounted on a conventional glass slide for diagnostic purposes. The glass slide, carrying the tissue section under examination, is subjected to certain reagents and stained in accordance with an established protocol in order to facilitate characterization and diagnosis of the tissue sample. The glass slide is then permanently "covered" with a chemical or glass coverslip to substantially avoid contamination and to permit long-term archiving of the slide.
One presently available glass coverslip has the same configuration as a conventional glass slide, i.e., substantially rectangular. The length and thickness are, by comparison, significantly reduced to decrease production costs. Another available glass coverslip is substantially circular, having a diameter corresponding to the width of a conventional glass slide.
Glass coverslips may be placed upon the tissue-carrying slide manually or by an automated coverslipper. One such automated system is shown in U.S. Pat. No. 3,833,449, and the teachings thereof are incorporated herein by reference. Typically the glass coverslips are vertically stacked in a housing, and an individual coverslip is placed upon the glass slide by either a piston-like mechanism (which pushes the uppermost coverslip in the housing onto the glass slide) or a vacuum mechanism (which lifts the top coverslip for appropriate placement and release).
Moisture between adjacent coverslips in the housing substantially interferes with the covering process and equipment. That is, condensation interposed adjacent stacked coverslips causes adherence, or "sticking," such that more than one coverslip is extracted by a single covering operation. The result is often one or more broken coverslips and a certain amount of "downtime" for maintenance of the system.
For archiving, it is desirable to permanently affix the coverslip to the glass slide. This allows the analyzed specimen to be stored for future reference thereto. Glues are typically used to permanently bond the coverslip to the glass slide, over the stained tissue sample. Such a glue is usually applied manually to either the coverslip or glass slide.
There is a continuing need for an improved coverslip that avoids or overcomes the foregoing deficiencies.
Summary of the Invention
An embodiment of the invention is directed to a pre-glued coverslip having a roughened glue surface. The invention is also directed to a method of making a pre-glued coverslip comprising applying an essentially flat glue surface to a coverslip and then disrupting the essentially flat glued surface of a pre-glued coverslip thereby reducing its tendency to stick to another coverslip. Another embodiment of the invention is a coverslip that has the glue spayed on in stripes thereby forming intervening channels of glue so that channels of air communicate with the edge of the coverslip.
Brief Description of the Drawings Figures 1 A-IB are photographs of a pre-glued glass coverslip (IA) and a roughened pre-glued glass coverslip (IB).
Figure 2 is a photomicrograph of the roughened coverslip of Figure IB at 15x power, showing with more detail the scratches in the glue surface.
Figure 3 is a front elevational diagram of a pre-glued coverslip. Description of the Preferred Embodiments
The invention is an improvement upon the pre-glued coverslip described in U.S. Patent No. 6,759,011 (Richards, et. al.), hereby incorporated by reference. However, this improvement is potentially applicable to any coverslip. hi the '011 patent there is described a pre-glued coverslip. Coverslips are usually stored arranged in a stack and then dispensed as needed by "peeling" them apart one-at-a-time. Since they are very thin and tend to stick together, many means have been pursued in the past to counter their tendency to stick together. It has been found that elevated humidity will worsen this tendency of the glued side and the non-glued side of an adjacent coverslip to stick together. It is postulated that this may be due to Van der Vaals forces. The improvement is directed to interrupting the tendency of objects in close proximity to stick together, and in one embodiment the invention is a slight roughening of the surface of the glue which results in a stick-free pre- glued coverslip. It is postulated that this roughening disrupts the Van de Vaals forces holding the closely-aligned surfaces together.
The prior art pre-glued coverslip, in a high humidity environment, had a sticking rate in excess of 20% after 24 or more hours of exposure, hi 380 trials of the roughened coverglass, the rate has dropped to 0%. The pre-glued coverslip of the 6,759,011 patent describes a coverslip having protuberances applied to one side and glue to the other. The present invention is not so limited, and any pre-glued coverslip may be used. whether it has protuberances on the opposing side or not. With respect to Figure 3, the stackable non-stick coverslip 10 has an adhesive 52 applied to a central region, generally designated 54, of the bottom surface 30B. The adhesive 52 is preferably a liquid that dries, upon application to the coverslip 10, to a tackless or only slightly tacky state. The adhesive 52 is activated or partially dissolved by a solvent, prior to placement onto a glass slide by applying solvent to the pre-glued coverslip surface, hi another embodiment, the solvent is applied manually, hi yet a further embodiment the adhesive maybe applied to less than the full area of the coverslip surface so that bare areas remain. This application of the adhesive may result in a pattern of stripes or layers that can have the same effect as a scratched or disrupted glue surface, that is, it will have areas of coverage separated by gaps that will allow air to flow between the glued areas (an "open-access" pattern). The adhesive may be applied via sprayer, mechanical applicator, or any other method for applying viscous liquids to the surface of glass.
As the activated adhesive 52 again dries, the coverslip 10 is affixed or bonded to the top surface of the glass slide. The glass slide can then be stored for future analysis and study or as a permanent record of the analysis preformed.
The adhesive 52 is preferably oil-based or water-insoluble, such that the solvent is non-aqueous, i.e., hydrophobic or lipophilic. Acrylic copolymers such as Acryloid® A-21, commercially available from Rohm and Haas, Philadelphia, Pa., are suitable. Other suitable adhesives include olefϊn-based materials, e.g., vinyl and acrylate based polymers; cellulose acetates; cyanoacrylates; silicone-containing materials including silane- and siloxane- terminated monomer based polymers; polytetrafluoroethylene based adhesives; and hydrocarbon based polymers. Suitable solvents to render the adhesive 52 tacky include aromatic hydrocarbons such as toluene, xylene, and benzene; silicones such as dimethicones, cyclomethicones and substituted siloxanes; aromatic and aliphatic hydrocarbons; alkyl esters; benzyl or alkyl benzoates; alkyl, alkoxyalkyl and glyceryl esters; and mixtures thereof. While an oil-based or water-insoluble solvent is preferred, a water- based solvent, such as Shur/Mount Liquid Mounting Medium (VWR Cat. No. 15148-062), may be utilized with certain stains.
With respect to Figures 1 and 2, the invention will now be described in more detail. There are many conceivable ways to disrupt the Van der Vaals forces, hi the present invention to accomplish this, the dried glue surface was lightly sandpapered to give the surface shown in Figure 1 (shown on the right), and in the close-up photomicrograph in Figure 2. The roughening process used included applying very light hand pressure and passing the glue side of the preglued coverslip over 400 grit sander paper, using 2 or 3 strokes in the direction of the long axis of the coverslip. Another roughening embodiment may involve applying the glue in a manner that leaves a textured surface once cured. Roughening methods might include: rubbing with sand paper, steel wool, emery board, wire brush etc.; sand or bead blasting. Applying a rough coating might be accomplished by a sputtering application, impressing a pattern before the glue is fully cured, or applying portions of the glue in more than one pass. An automated industrial process of any of the above would likely come at the glass sheet level, before any coverslips are cut.
The pattern need not be longitudinal scratches as we have done, but could also be transverse. Moreover, a grid or even random pattern of raised or removed material (i.e., surface disruption) would be sufficient. The scratch depth need only be enough to eliminate the sticking, but not so much as to cause air bubbles to form under the coverslip with the coverslipper in operation.
Although certain presently preferred embodiments of the invention have been described herein, it will be apparent to those skilled in the art to which the invention pertains that variations and modifications of the described embodiments may be made without departing from the spirit and scope of the invention. Accordingly, it is intended that the invention be limited only to the extent required by the appended claims and the applicable rules of law.

Claims

Claims
I claim:
1 A pre-glued coverslip comprising a roughened glue surface.
2. The pre-glued coverslip of claim 1 wherein the glue is dried upon the surface of the coverslip.
3. The pre-glued coverslip of claim 2 wherein the glue is first applied evenly and allowed to dry to a relatively smooth surface, and later roughened.
4. The pre-glued coverslip of claim 1 wherein the glue is water insoluble.
5. The pre-glued coverslip of claim 1 wherein the glue is applied in stripes.
6. A pre-glued coverslip comprising a roughened glue surface wherein the surface is scratched with an abrasive.
7. The pre-glued coverslip of claim 6 wherein the scratches penetrate the glue to the coverslip.
8. The pre-glued coverslip of claim 6 wherein the scratches provide an air path from the periphery of the coverslip to an area inside the coverslip.
9. A method of making a pre-glued coverslip comprising
(a) applying an essentially flat glue surface to a coverslip; and
(b) disrupting the essentially flat glued surface of a pre-glued coverslip thereby reducing its tendency to stick to another coverslip.
10. The method of claim 9 wherein disrupting the surface comprises scratching depressions into the glue surface.
11. The method of claim 10 wherein scratching comprises using sandpaper.
12. The method of claim 10 wherein scratching comprises contacting said flat glue surface with an instrument capable of removing a channel of glue thereby creating an airway.
13. A method of making a pre-glued glass coverslip comprising applying liquid glue to less than all of the available surface of the glass in a predetermined open-access pattern thereby allowing air to flow in and out of the glued area.
14. The method of claim 13 wherein the glue is sprayer-applied in a pattern of stripes.
PCT/US2005/039152 2004-11-08 2005-10-27 Preglued coverglass with roughened glue surface WO2006052492A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US62634004P 2004-11-08 2004-11-08
US60/626,340 2004-11-08

Publications (1)

Publication Number Publication Date
WO2006052492A1 true WO2006052492A1 (en) 2006-05-18

Family

ID=35673306

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2005/039152 WO2006052492A1 (en) 2004-11-08 2005-10-27 Preglued coverglass with roughened glue surface

Country Status (1)

Country Link
WO (1) WO2006052492A1 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017042115A1 (en) 2015-09-11 2017-03-16 Elvesys Liquid sample support substrate, assembly comprising such a substrate and use thereof
WO2020199125A1 (en) * 2019-04-02 2020-10-08 京东方科技集团股份有限公司 Biological information detection substrate and gene chip

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4428793A (en) * 1981-08-25 1984-01-31 Meisei Electric Co., Ltd. Preparation method for a microscopic specimen and a device therefor
US6759011B1 (en) * 1999-11-22 2004-07-06 Ventana Medical Systems, Inc. Stackable non-stick coverslip

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4428793A (en) * 1981-08-25 1984-01-31 Meisei Electric Co., Ltd. Preparation method for a microscopic specimen and a device therefor
US6759011B1 (en) * 1999-11-22 2004-07-06 Ventana Medical Systems, Inc. Stackable non-stick coverslip

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017042115A1 (en) 2015-09-11 2017-03-16 Elvesys Liquid sample support substrate, assembly comprising such a substrate and use thereof
US10471430B2 (en) 2015-09-11 2019-11-12 Elvesys Substrate for supporting liquid sample, an assembly comprising such a substrate and use thereof
WO2020199125A1 (en) * 2019-04-02 2020-10-08 京东方科技集团股份有限公司 Biological information detection substrate and gene chip
US11583856B2 (en) 2019-04-02 2023-02-21 Beijing Boe Optoelectronics Technology Co., Ltd. Bio-information detection substrate and gene chip

Similar Documents

Publication Publication Date Title
US10578524B2 (en) Analytic substrate coating apparatus and method
US3498860A (en) Process of mounting precoated cover glass for microscope slides
AU2019201130B2 (en) Automated coverslipper and methods of use
US6759011B1 (en) Stackable non-stick coverslip
WO2016150446A1 (en) Method and apparatus for attaching, detecting and retrieving a single cell on a surface
WO2006052492A1 (en) Preglued coverglass with roughened glue surface
CA2368753C (en) Stackable non-stick coverslip
EP1526369B1 (en) Coverslip and method for applying a coverslip to a glass slide
JP2015519041A5 (en)
KR101042685B1 (en) Film Parts For Transcribing Fingerprint And The Manufacturing Method thereof
JPS6344761Y2 (en)

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KM KN KP KR KZ LC LK LR LS LT LU LV LY MA MD MG MK MN MW MX MZ NA NG NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SM SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LT LU LV MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase

Ref document number: 05814847

Country of ref document: EP

Kind code of ref document: A1