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WO2017045712A1 - Agencement et procédé de fourniture d'un échantillon pour inspection par un dispositif d'imagerie - Google Patents

Agencement et procédé de fourniture d'un échantillon pour inspection par un dispositif d'imagerie Download PDF

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Publication number
WO2017045712A1
WO2017045712A1 PCT/EP2015/071244 EP2015071244W WO2017045712A1 WO 2017045712 A1 WO2017045712 A1 WO 2017045712A1 EP 2015071244 W EP2015071244 W EP 2015071244W WO 2017045712 A1 WO2017045712 A1 WO 2017045712A1
Authority
WO
WIPO (PCT)
Prior art keywords
sample
arrangement
coverslip
imaging device
capillary
Prior art date
Application number
PCT/EP2015/071244
Other languages
English (en)
Inventor
Oliver Hayden
Lukas RICHTER
Oliver Schmidt
Sandro Francesco Tedde
Original Assignee
Siemens Healthcare Gmbh
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 Siemens Healthcare Gmbh filed Critical Siemens Healthcare Gmbh
Priority to PCT/EP2015/071244 priority Critical patent/WO2017045712A1/fr
Publication of WO2017045712A1 publication Critical patent/WO2017045712A1/fr

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00009—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with a sample supporting tape, e.g. with absorbent zones
    • 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
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/34—Microscope slides, e.g. mounting specimens on microscope slides
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N2021/0346—Capillary cells; Microcells
    • G01N2021/035—Supports for sample drops
    • G01N2021/0353—Conveyor of successive sample drops
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N2021/0357—Sets of cuvettes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N2021/0364—Cuvette constructions flexible, compressible

Definitions

  • the present invention relates to techniques for providing samples to be investigated by medical devices and more particularly to techniques for providing samples to be investigated by an imaging device.
  • imaging devices for example interferometric imaging devices like digital holographic microscopy devices, have been improved in terms of their speed of operation and are capable of generating images of a sample at a high speed.
  • imaging devices for example interferometric imaging devices like digital holographic microscopy devices, have been improved in terms of their speed of operation and are capable of generating images of a sample at a high speed.
  • imaging devices for example interferometric imaging devices like digital holographic microscopy devices, have been improved in terms of their speed of operation and are capable of generating images of a sample at a high speed.
  • the use of such imaging devices in their full capacity is still limited because these imaging devices depend on a rate at which the sample is provided or fed to the device.
  • providing the sample for inspection are usually manual and are performed by operators who place the sample into a field of view of the imagining device.
  • an object of the present technique is to provide a technique for providing a sample for inspection by an imaging device.
  • the technique is aimed at providing the sample to the imaging device efficiently.
  • an arrangement for providing a sample for inspection by an imaging device includes a substrate and a
  • the substrate has a surface.
  • the surface has a sample receiving region and a capillary forming region.
  • the sample receiving region is adjacent to or
  • the capillary forming part includes a coverslip and a spacer.
  • the coverslip is positioned upon or over the capillary forming region of the surface of the substrate.
  • the coverslip covers the capillary forming region i.e. the coverslip is aligned laterally with the capillary forming region but hovers over the capillary forming region at a distance removed from the capillary forming region.
  • the coverslip is transparent and can be positioned in a Field of View, hereinafter also referred to as the FOV, of the imaging device.
  • the spacer is positioned in between the substrate and the coverslip i.e. the spacer is sandwiched in between the coverslip and the surface of the substrate.
  • a capillary volume is formed between the
  • the capillary volume has a fixed known volume and dimension, a precisely known volume of the sample is positioned in the FOV of the imaging device. Furthermore, the part of the volume of the sample in the capillary volume has fixed dimension so a depth of the sample is known which may be advantageous for imaging as well as post imaging analysis. Furthermore, since the only
  • Positioning of the sample in FOV, or more particularly, positioning of a fixed volume of the sample in the FOV, of the imaging device is performed automatically by the capillary action of the capillary volume and is independent of the operator' s
  • the sample is accurately provided to the imaging for inspection by the imaging device and this in turn
  • the substrate is an elongated body.
  • the arrangement includes a plurality of capillary forming parts.
  • the capillary forming parts are arranged at predefined intervals on the substrate.
  • the pre-defined intervals may be regular, i.e. consecutive capillary forming parts are arranged at a same distances, or may be irregular i.e. consecutive capillary forming parts are arranged at varying distances.
  • the arrangement can be used for providing a number of samples to be inspected by one or more imaging devices.
  • At least one of the substrate, the coverslip and the spacer is flexible. This makes alignment of the arrangement with the FOV easier, and furthermore pre-use or post-use storage of the arrangement is simpler as the arrangement is capable of being folded into layers or rolls. Moreover, flexible parts do not break as easily as inflexible or rigid parts.
  • the capillary forming region includes a hydrophilic layer.
  • the hydrophilic layer further facilitates suctioning of the sample from the sample receiving region into the capillary volume or over the capillary forming region of the surface of the substrate.
  • the capillary forming region further includes a functionalizing layer for interacting with at least one component of the sample, for example for binding with a component of the sample.
  • the component of the sample is positioned at the capillary forming region of the surface of the substrate within the capillary volume.
  • the component of the sample has a very precise position during the imaging performed with the imaging device.
  • At least one of the sample receiving regions and a top surface of the coverslip includes a hydrophobic layer.
  • the hydrophobic layer ensures that the sample is pushed away from top of the layer.
  • the hydrophobic layer is on the sample receiving region, the sample is pushed away by the hydrophobic layer facilitating movement of the sample into the capillary volume.
  • any spills from the sample onto the top surface of the coverslip are pushed off the top surface of the coverslip ensuring a clean top surface of the coverslip which increases the quality of imaging compared to a scenario where there are spills or residues of the sample on the top surface of the cover slip.
  • the arrangement can be winded up or arranged or aligned in a roll. This ensures that when the arrangement is deployed with the imaging device, the arrangement uses minimal space and implementing the arrangement with the imaging device becomes easier.
  • the arrangement in form of the roll is capable of being stored in smaller space.
  • the substrate is disc shaped and one or more capillary forming parts are arranged on the substrate in a non-linear manner. This provides a compact design for the arrangement.
  • a system for inspecting a sample is presented. The system includes an arrangement according to the first aspect presented
  • the coverslip of the arrangement is such positioned such that the coverslip is placed in the FOV of the imaging device.
  • the sample is provided accurately and manual intervention or expertise in providing the sample is at least partially obviated and thus the sample is provided to the imaging device at a high rate compared to a manual providing of the sample to an imaging device or setup.
  • the system includes at least one additional imaging device.
  • the coverslip of the first imaging device includes at least one additional imaging device.
  • additional imaging device is positioned such that the
  • coverslip of the additional imaging device is in an
  • the system further includes a sample deposition module.
  • the sample deposition module provides the sample to the sample receiving region.
  • manual intervention to pick and place the sample into the sample receiving region is at least partially reduced. This also ensures that chances of manual error in placing the sample are reduced.
  • the sample deposition module provides the sample to the sample receiving region intermittently. This ensures that multiple samples, same or different, are positioned on the substrate and the system is then further suited to carry out imaging of several samples by one or more imaging devices in the system.
  • the system includes a moving mechanism. The moving mechanism moves the arrangement of the system in a direction parallel to a horizontal plane along the FOV of the imaging device. This provides greater flexibility in integrating different imaging devices in the system as the sample can be moved from FOV of one device to another .
  • the moving mechanism is configured to rotate the arrangement.
  • the readout or imaging by the imaging device is performed after a rotational motion of the arrangement aligns the sample in the capillary volume with the FOV of the imaging device.
  • the system further includes a focusing mechanism. The focusing mechanism moves the arrangement perpendicular to the horizontal plane. This helps in achieving a placement of the sample in which the sample is focused for the imaging device of the system.
  • a method for providing a sample for inspection by an imaging device is presented.
  • an arrangement according to the first aspect of the present technique, presented hereinabove is provided.
  • a first specimen of the sample is placed at a first position of the sample receiving region.
  • At least a part of the first specimen of the sample is drawn into a capillary volume adjoining the first position.
  • At least a part of the first specimen of the sample is drawn into the capillary volume adjoining the first position by a capillary action of the capillary volume adjoining the first position.
  • the coverslip adjoining the first position of the sample receiving region is positioned in the FOV of the imaging device.
  • a second specimen of the sample is placed at a second position of the sample receiving region.
  • the step of placing the second specimen of the sample at the second position of the sample receiving region is performed subsequent to placing the first specimen of the sample at the first position of the sample receiving region.
  • At least a part of the second specimen of the sample is drawn into a capillary volume adjoining the second position by a capillary action of the capillary volume adjoining the second position.
  • the arrangement is moved in a direction parallel to a horizontal plane, and as a result the sample at the first position is moved out of the FOV of the imaging device.
  • the horizontal plane is along the FOV of the imaging device.
  • the coverslip adjoining the second position is positioned in the FOV of the imaging device.
  • the arrangement is further moved perpendicular to the horizontal plane. In the method, this helps in achieving a placement of the sample in which the sample is focused for the imaging device.
  • the imaging device should be used for inspecting multiple samples with a high throughput, for example when investigating a given blood sample by several imaging devices or when investigating different blood samples by one or more imaging devices.
  • FIG 1 schematically illustrates an exemplary embodiment of a system of the present technique
  • FIG 2 schematically illustrates a cross-sectional view of an exemplary embodiment of an arrangement of the present technique; schematically illustrates the exemplary embodiment of the arrangement of FIG 2 with a sample; schematically illustrates the exemplary embodiment of the arrangement of FIG 3 with a capillary action on the sample; schematically illustrates another exemplary
  • FIG. 1 schematically illustrates yet another exemplary embodiment of the system of FIG 1 having a moving mechanism and a focusing mechanism; schematically illustrates a top-view of an
  • FIG 14 schematically illustrates yet another exemplary embodiment of the arrangement in form of a disc; in accordance with aspects of the present technique.
  • FIG 1 an exemplary embodiment of an arrangement 1 of the present technique is schematically presented.
  • the arrangement 1 is for providing a sample 20 for inspection by an imaging device 40.
  • the imaging device 40 includes, but is not limited to, devices for microscopy, interferometry or digital
  • Such imaging devices 40 have a Field of View 50, hereinafter also referred to as the FOV 50, which represents the observable range that can be imaged by the imaging device 40.
  • FOV 50 Field of View 50
  • FIG 2 schematically depicts a cross- sectional view of an exemplary embodiment of the arrangement 1.
  • FIG 3 schematically shows the exemplary embodiment of the arrangement 1 with the sample 20 placed in the arrangement 1.
  • FIG 4 schematically shows the exemplary embodiment of the arrangement 1 depicting a capillary action on the sample 20 placed in the arrangement 1.
  • the arrangement 1 includes a substrate 10 and a capillary forming part 30.
  • the substrate 10 has a surface 11. There are two different, but adjoining or contiguous, regions on the surface 11 of the substrate 10. One of these two regions is a sample receiving region 12 and the other one is a capillary forming region 16.
  • the sample receiving region 12 is adjacent to the capillary forming region 16, which is to be understood as the sample receiving region 12 and the capillary forming region 16 are located next to each other.
  • the sample receiving region 12 is adjacent to the capillary forming region 16, which is to be understood as the sample receiving region 12 and the capillary forming region 16 are located next to each other.
  • the arrangement 1 further includes a capillary forming part 30.
  • the capillary forming part 30 includes a coverslip 32 and a spacer 34.
  • the coverslip 32 is positioned upon or over the capillary forming region 16 of the surface 11 such that the coverslip 32 covers the capillary forming region 16.
  • coverslip 32 is physically removed from, i.e. not touching, the surface 11, but rather the coverslip 32 is positioned laterally at a distance from the surface 11 along a vertical axis 9 of the imaging device 40.
  • the coverslip 32 is aligned parallel to the capillary forming region 16 such that the coverslip 32 at least partially covers or hovers over or shadows the capillary forming region 16 on the surface 11 of the substrate 10. It may be noted that when viewed from top, i.e. along the vertical axis 9, the coverslip 32 shadows or hides or covers the capillary forming region 16, however, the sample receiving region 12 is free of the coverslip 32 i.e.
  • the coverslip 32 does not cover the sample receiving region 12 when viewed from side of the imaging device 40 towards the arrangement 1 along the vertical axis 9.
  • the coverslip 32 is made out of a transparent material and thus is light- transmissive .
  • materials for the coverslip 32 include, but are not limited to, glass or polymers, for example transparent plastics.
  • the coverslip 32 is to be positioned in the FOV 50 of the imaging device 40 in order to allow examination of the sample 20, when the sample 20 is present beneath the coverslip 32, by the imaging device 40.
  • the spacer 34 in between of the substrate 10 and the coverslip 32, the spacer 34 is arranged.
  • the spacer 34 is sandwiched between the surface 11 and the coverslip 32 such that at least a part of the capillary forming region 16 contiguous with or adjacent to the sample receiving region 12 is free of the spacer 34.
  • the substrate 10, the spacer 34 and the coverslip 32 are aligned parallel to each positioned at different locations along the vertical axis 9.
  • coverslip 32, an inner side surface 35 of the spacer 34 and the capillary forming region 16 on the surface 11 of the substrate 10 form a capillary volume 36. Since the substrate 10, the coverslip 32 and the spacer 34 are in fixed
  • the predefined volume depends on a height of the spacer 34 i.e. a separation between the surface 11 and the inner surface 39 of the coverslip 32, and also depends on an area of the inner surface 39 of the coverslip 32 and an area of the capillary forming region 16.
  • the capillary volume is a long and slender elongated volume having dimensions that support flow of the sample 20 or at least a part of the sample 20 into the capillary volume 36 by a capillary action of the capillary volume 36, i.e. the sample 20 or a part of the sample 20 flows into the capillary volume 36 by capillary action and does not require any other external force or assistance for flowing from the sample receiving region 12 to the capillary forming region 16 in the capillary volume 36.
  • the amount of the capillary volume 36 may be from one to a few micro liters ( ⁇ ) .
  • the capillary volume 36 may be
  • the sample 20 is placed onto the sample receiving region 12 on the surface 11 of the substrate 10.
  • the sample 20 includes, but is not limited to, substances like blood, urine, etc.
  • the sample 20 may be understood as a blood sample 20 which is placed on the sample receiving region 12 in form of a drop.
  • Capillary forces from the capillary volume 36 act on the sample 20 and at least a part of the sample 20, as shown in FIG 4, is suctioned into the capillary volume 36 along a direction depicted by an arrow marked with reference numeral 2.
  • the sample 20 may be for example blood plasma containing a component 3, for example a red blood cell 3, hereinafter also referred to the RBC 3.
  • the capillary action in the direction 2 some of the sample 20 along with the RBCs 3 move into the capillary volume 36.
  • the part of the sample 20 in the capillary volume 36 has a fixed height i.e. same as the height of the spacer 34 and has a fixed volume i.e. same as the volume of the capillary volume 36.
  • the sample 20 with a known height or depth i.e. extension of the sample 20 along the vertical axis 9 and with a known volume is thus positioned beneath the coverslip 32 which in turn is
  • the substrate 10 may be an elongated body like a tape.
  • the substrate 10 is extended along a direction 51 substantially parallel to the FOV 50 or more particularly, to a horizontal plane 6 along the FOV 50.
  • the arrangement 1 comprises a plurality of capillary forming parts 30. Consecutive
  • capillary forming parts 30 are arranged at predefined intervals 37, 38 on the substrate 10.
  • the intervals 37, 38 may be same or may differ from each other.
  • the imaging device 40 may have variable configurations for example, in an exemplary embodiment the imaging device 40 may be a reflective sensing device, as depicted in FIG 1, and then the substrate 10 has a reflective surface, for example a mirror, as the surface 11, whereas in another exemplary embodiment the imaging device 40 may be a transmission or diffraction or interference sensing device having a light source 46 and a detector 48, as depicted in FIG 5, and then the substrate 10 has a transparent surface, for example glass or a transparent polymer, as the surface 11.
  • the substrate 10 and/or the coverslip 32 and/or the spacer 34 may be made out of a flexible material for example a transparent polymer.
  • the term "flexible" herein includes, that the material is able to deform elastically and to fit, by
  • the material may be able to return back to its original shape when the applied stress is removed.
  • the arrangement 1 can be wound up or aligned or arranged as a roll 8 as shown in FIG 10.
  • the arrangement 1 may have the roll 8 that opens up and presents a part of the surface 11 for receiving the sample in the sample receiving region 12, and imaging is done through the coverslip 32 as the surface 11 is opened up and out of the roll 8, as shown in FIG 10.
  • the capillary forming part 30 is arranged in a linear fashion along the substrate 10.
  • the capillary forming part 30 is not arranged in a linear fashion along the substrate 10 but rather in a circular manner as shown in FIG 14.
  • the substrate 10 is disc shaped as shown by reference numeral 17 in FIG 14.
  • the capillary forming part 30 is formed or positioned on the disc 17 wherein the sample receiving surface 12 and the capillary forming region 16 have the shape of adjacent spirals or concentric circles (not shown) .
  • the disc 17 rotates along a central point 18 of the disc 17 and thereby presents the sample receiving region 12 to the sample depositing module 4 for receiving the sample 20.
  • the sample depositing module 4 deposits the sample 20 onto the sample receiving region 12.
  • the rotating disc 17 also presents the coverslip 32 of the capillary forming part 30 to the FOV 50 of the imaging device 40 such that the coverslip 32 is positioned in the Field of View 50 of the imaging device 40 thereby enabling the imaging device 40 to acquire images of the sample 20 in the capillary volume 36 and in the FOV 50 of the imaging device 40.
  • FIG 8 and FIG 9 both illustrate a cross section of the arrangement 1 according to the present technique.
  • the capillary forming region 16 may include a hydrophilic layer 15.
  • the hydrophilic layer 15 may be present as a coating on the capillary forming region 16 of the surface 11. As hydrophilic substances attract aqueous substances, the hydrophilic layer 15 ensures that the sample 20 moves in a direction 2 to the capillary forming region 16 on the surface 11 of the substrate 10 when the sample 20 has aqueous components.
  • the hydrophilic layer 15 also helps to retain the sample 20 once the sample 20 has positioned itself on the hydrophilic layer 15.
  • Such hydrophobic materials used as a layer or coating are well known in the art of chemistry and are thus not explained herein in details for sake of brevity .
  • a part of the sample receiving region 12 and/or a top surface 33 of the coverslip 32 may further include a hydrophobic layer 13 in an exemplary embodiment of the arrangement 1, without the or besides the hydrophilic layer 15.
  • the hydrophilic layer 15 may be present as a coating on the sample receiving region 12 and/or the top surface 33 of the coverslip 32.
  • the hydrophobic layer 13 rejects or pushes away the aqueous components in the sample 20.
  • movement of the sample 20 is enhanced or facilitated in the direction 2.
  • the sample receiving region 12 and the capillary forming region 16 are adjacent to each other, the sample 20 moves in the direction 2.
  • the top surface 33 of the coverslip 32 may also include a hydrophobic layer 13, any accidental deposits or residues of the sample 20 like spillovers, get removed from the top surface 33 of the coverslip 32 and thus chances of
  • the capillary forming region 16 includes a functionalizing layer 14, as depicted in FIG 9.
  • the functionalizing layer 14 may be present as a coating on the capillary forming region 16 of the surface 11, without the or besides the hydrophilic layer 14 shown in FIG 8.
  • the functionalizing layer 14 is made of a material that interacts with at least one component 3 of the sample 20, for example the functionalizing layer 14 may be formed of a specific antibody to bind a specific protein on a cell surface of the component 3 of the sample 20.
  • the component 3 of the sample 20 may be freely suspended in the sample 20 in general.
  • the functionalizing layer 14 at least one
  • component 3 of the sample 20 may interact with the
  • the type of interaction includes, but is not limited to, chemical bonds like ionic bonding, covalent bonding, metallic bonding and hydrogen bonding. Therefore, it is ensured that the component 3 of the sample 20 is securely attached to the surface 11 when the sample 20 moves in the direction 2 and into the capillary forming region 16 of the substrate 10.
  • the component 3 of the sample 20 includes, but is not limited to, specific cells that are particularly desired to be imaged by the imaging device 40. Such hydrophobic materials used as a layer or coating are well known in the art of biochemistry and are thus not explained herein in details for sake of brevity. Thus by not employing or by employing the
  • the components 3 may be imaged, respectively, in suspension or as adhered to the surface 11 of the substrate 10 within the capillary volume 36.
  • FIG 7 a top view of the arrangement 1 has been depicted.
  • the substrate 10 the coverslip 32 and the spacer 34 are all elongated, i.e. like a tape.
  • the substrate 10 is elongated and a plurality of the spacers 34 are positioned at different locations on the surface 11 of the substrate 10 and each spacer 34 has its corresponding coverslip 32.
  • the spacers are positioned in a spiral.
  • the substrate 10 and the spacer 34 is elongated and a plurality of the coverslips 32 are positioned at different locations on the spacer 34.
  • the substrate 10 and the coverslips 32 is elongated and a plurality of the spacers 34 are
  • FIG 1 a system 100 for inspecting the sample 20 by an imaging device 40 is presented.
  • the system 100 includes an arrangement 1 and an imaging device 40.
  • the arrangement 1 is same as explained according to the first aspect of the present technique and particularly with reference to FIGs 1 to 9 hereinabove.
  • the coverslip 32 of the arrangement 1 is positioned such that the coverslip 32 is within the FOV 50 of the imaging device 40.
  • the imaging device 40 may be either stationary or movable. More clearly, the imaging device 40, and as a result the FOV 50, may be configured to move along its axis 9 and/or along the
  • the system 100 may include one imaging device 40 as shown in FIG 6 or may include a plurality of imaging devices, as shown for example in FIG 10, where the system 1 includes the imaging device 40, an additional imaging device 42 with an additional field of view 52 and a further additional imaging device 43 with a further additional field of view 53.
  • a relative orientation of the imaging devices 40, 42, 43 may be changed with respect to the arrangement 1, for example by a moving mechanism 5 that moves the arrangement 1 parallel to the axis 51 and positions the different samples 20 in the FOVs 50, 52, 53, as depicted in FIG 10.
  • the sample 20 may, for example, be placed on the substrate 10.
  • the coverslip 32 may be positioned in the FOV 52 and the sample 20 is imaged by the imaging device 42.
  • the arrangement 1 is moved in the direction 51 by the moving mechanism 5 and the coverslip 32 is positioned in the FOV 50 and imaged by the imaging device 40.
  • the arrangement 1 is again moved by the moving mechanism 5 and the coverslip 32 is positioned in the FOV 53 and imaged by the imaging device 43.
  • the imaging devices 40, 42, 43 may differ in their imaging techniques, and also have different magnifications or operative wave lengths.
  • the system 100 includes a focusing mechanism 7.
  • the focusing mechanism 7 moves the arrangement 1 perpendicular to the horizontal plane 6 of the Field of View 50 of the imaging device 40 along a direction 71 parallel to the vertical axis 9 shown in FIG 1.
  • the imaging device 40 is stationary, still different settings for imaging are possible.
  • the system 100 includes a sample
  • the sample deposition module 4 provides the sample 20, continuously or intermittently, to the sample receiving region 12. Thus, in this embodiment of the system 100, the sample 20 does not have to be provided to the sample receiving region 12 manually.
  • FIG 11 a flow chart representing an
  • a first specimen 21 of the sample 20 is placed on a first position 121 of the sample receiving region 12, as shown in FIG 12.
  • the first specimen 21 is placed such that at least a part of the first specimen 21 of the sample 20 is drawn into the capillary volume 36 adjoining the first position 121 of the sample receiving region 12.
  • the way the first specimen 21 of the sample 20 is placed is illustrated in FIG 3.
  • the first specimen 21 of the sample 20 is drawn into the capillary volume 36 by a capillary action of the capillary volume 36 adjoining the first position 121, as depicted in FIG 4.
  • step 400 the coverslip 32 adjoining the first position 121 of the sample receiving region 12 is positioned in the FOV 50 of the imaging device 40, as depicted in FIGs 12. It may be noted by one skilled in the art, that step 300 and 400 may be performed simultaneously or step 300 may be performed after step 400 or vice versa.
  • the method 1000 may further include a step 500.
  • a second specimen 22 of the sample 20 is placed at a second position 122 of the sample receiving region 12 subsequent to the step 300.
  • the second specimen 22 of the sample 20 is placed on the second position 122 such that at least a part of the second specimen 22 of the sample 20 is drawn into the capillary volume 36 adjoining the second position 122 of the sample receiving region 12 by a capillary action of the capillary volume 36 adjoining the second position 122, as depicted in FIG 12.
  • the arrangement 1 is moved in the direction 51 parallel to the direction 51 as shown in FIG 13.
  • Step 700 is performed subsequent to the step 400.
  • the arrangement 1 is further moved in a step 800 perpendicular to the plane 6 in the direction 71 by the focusing mechanism 7 as shown in FIG 6.
  • the step 800 may be performed simultaneously with the step 400 and/or the step 700.

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  • Analytical Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Optics & Photonics (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)

Abstract

La présente invention concerne un agencement, un système et un procédé pour la fourniture d'un échantillon pour examen par un dispositif d'imagerie. L'agencement comprend un substrat et une partie de formation de capillaire. Le substrat comprend une région de réception d'échantillon et une région de formation de capillaire sur une surface du substrat. La région de réception d'échantillon reçoit l'échantillon. La région de réception d'échantillon est adjacente à la région de formation de capillaire. La partie de formation de capillaire comprend une lamelle et un élément d'espacement. La lamelle est positionnée au-dessus de la région de formation de capillaire de la surface du substrat de sorte que la lamelle recouvre la région de formation de capillaire. La lamelle est transparente et est positionnée dans un champ de vision du dispositif d'imagerie. L'élément d'espacement est positionné entre le substrat et la lamelle de sorte qu'un volume capillaire soit formé entre la lamelle, l'élément d'espacement et la région de formation de capillaire de la surface.
PCT/EP2015/071244 2015-09-16 2015-09-16 Agencement et procédé de fourniture d'un échantillon pour inspection par un dispositif d'imagerie WO2017045712A1 (fr)

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3609045A (en) * 1969-10-01 1971-09-28 Kurt Stein Apparatus for storing and visibly comparing the optical properties of minature samples
US5248479A (en) * 1990-11-16 1993-09-28 Abbott Laboratories Agglutination reaction device having geometrically modified chambers
WO2005100539A2 (fr) * 2004-04-07 2005-10-27 Levine, Robert, A. Chambre jetable pour l'analyse de liquides biologiques
WO2010063293A1 (fr) * 2008-12-05 2010-06-10 Unisensor A/S Sectionnement optique d'un échantillon et détection de particules dans un échantillon
US20120088230A1 (en) * 2010-10-11 2012-04-12 Monique Givens System And Method For Cell Analysis
WO2012050809A1 (fr) * 2010-09-29 2012-04-19 Siemens Healthcare Diagnostics Inc. Revêtement hydrophile pour surfaces non poreuses et dispositifs microfluidiques contenant ce revêtement
WO2014137996A2 (fr) * 2013-03-04 2014-09-12 Liffmann, Stanley, M. Substrat pour manipulation d'échantillon

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3609045A (en) * 1969-10-01 1971-09-28 Kurt Stein Apparatus for storing and visibly comparing the optical properties of minature samples
US5248479A (en) * 1990-11-16 1993-09-28 Abbott Laboratories Agglutination reaction device having geometrically modified chambers
WO2005100539A2 (fr) * 2004-04-07 2005-10-27 Levine, Robert, A. Chambre jetable pour l'analyse de liquides biologiques
WO2010063293A1 (fr) * 2008-12-05 2010-06-10 Unisensor A/S Sectionnement optique d'un échantillon et détection de particules dans un échantillon
WO2012050809A1 (fr) * 2010-09-29 2012-04-19 Siemens Healthcare Diagnostics Inc. Revêtement hydrophile pour surfaces non poreuses et dispositifs microfluidiques contenant ce revêtement
US20120088230A1 (en) * 2010-10-11 2012-04-12 Monique Givens System And Method For Cell Analysis
WO2014137996A2 (fr) * 2013-03-04 2014-09-12 Liffmann, Stanley, M. Substrat pour manipulation d'échantillon

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