Methods, systems, and devices for sample interface
By designing the sample interface module, using a combination of cam plate and cover to design and fix the sample, and providing edge illumination through a built-in light source, the problem of unstable motion in the sample in situ analysis is solved, achieving high-quality image processing and imaging.
Patent Information
- Application Number
- CN202380056138.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2022-06-03
- Filing Date
- 2023-06-02
- Publication Date
- 2025-03-21
AI Technical Summary
During in-situ analysis, the motion of the sample needs to be minimized to ensure accurate image processing and imaging, however prior art is difficult to effectively fix the sample, providing appropriate test reagent volume and edge illumination.
A sample interface module (SIM) is designed, which includes components such as a stage body, a cover, a cam plate and a light source. By providing forces in the X and Y directions by the cam plate, the design of the cover and stage body ensures that the sample is also fixed in the Z direction, thereby achieving stable positioning of the sample. At the same time, the module has built-in light source for edge lighting.
Effectively fix the sample, reduce sample movement, ensure image processing accuracy and imaging quality, while providing appropriate probe reagent volume and edge illumination to support multiple detection and imaging.
Smart Images
Figure CN119677590A_ABST
Abstract
Description
Technical Field
[0001] The present disclosure relates to methods, systems and devices for sample interfaces. Specifically, the present disclosure describes sample interface devices and systems configured to secure a sample (eg, a biological sample) in an analytical instrument (eg, an in situ analytical instrument). Background Art
[0002] In situ analysis can be used to detect the presence of target molecules (e.g., RNA, DNA, proteins, antibodies, etc.) in their naturally occurring three-dimensional locations (i.e., in situ) in samples (e.g., biological samples). In preparation for in situ analysis, the sample can be positioned on a substrate (e.g., a glass slide), or the sample can be pre-positioned on a substrate and stored. The substrate (with the sample thereon) is then fixed in an in situ analysis system so that the sample can be repeatedly detected and imaged to determine the presence of the target molecule. The movement of the sample should be minimized to allow accurate image processing, such as image registration and / or image stitching. Therefore, methods, systems and devices are needed to connect the sample to an in situ analysis system so as to fix the sample for imaging, provide a volume for detecting reagents, and provide edge illumination of the sample. BRIEF DESCRIPTION OF THE DRAWINGS
[0003] FIG. 1A to FIG. 1I A sample interface module is shown in an open configuration according to an embodiment of the present disclosure. Figure 1A to Figure 1B is a perspective view of the sample interface module in the open configuration. Figure 1C is an enlarged view of a portion of the sample interface module. Figure 1D is a top view of the sample interface module in the open configuration. Figure 1E to Figure 1H is a side view of the sample interface module in the open configuration. Fig. 1I is a bottom view of the sample interface module in the open configuration.
[0004] FIG. 2A to FIG. 2H A sample interface module is shown in a closed configuration with a cartridge secured therein according to an embodiment of the present disclosure. FIG. 2A to FIG. 2B is a perspective view of the sample interface module in a closed configuration. Figure 2C is a top view of the sample interface module in a closed configuration. Figure 2D to Figure 2G is a side view of the sample interface module in a closed configuration. Figure 2H is a bottom view of the sample interface module in the closed configuration.
[0005] Figure 3 Shown is a cross-section of a sample interface module in a closed configuration according to an embodiment of the present disclosure.
[0006] 4A to 4H A sample device according to an embodiment of the present disclosure is shown.
[0007] FIG. 5A to FIG. 5H A carrier for a sample interface module according to an embodiment of the present disclosure is shown. FIG. 5A to FIG. 5B is a perspective view of a carrier for a sample interface module. FIG. 5C to FIG. 5F is a side view of a carrier for a sample interface module. Figure 5G is a top view of a carrier for a sample interface module. Figure 5H is a bottom view of a carrier for a sample interface module.
[0008] FIG. 6A to FIG. 6C A carrier for a sample interface module (without a top cover) is shown according to an embodiment of the present disclosure.
[0009] FIG. 7A to FIG. 7G A gasket for a sample device according to an embodiment of the present disclosure is shown.
[0010] Figure 8 A leak sensor of a sample interface module according to an embodiment of the present disclosure is shown.
[0011] 9A to 9E A riser and leveling subassembly according to an embodiment of the present disclosure is shown.
[0012] FIG. 10A to FIG. 10C An optical wetting consumable and waste container subassembly is shown according to an embodiment of the present disclosure. DETAILED DESCRIPTION
[0013] In situ analysis can be used to detect the presence of target molecules (e.g., RNA, DNA, proteins, antibodies, etc.) in their naturally occurring three-dimensional locations (i.e., in situ) in samples (e.g., biological samples). In preparation for in situ analysis, the sample can be positioned on a substrate (e.g., a glass slide), or the sample can be pre-positioned on a substrate and stored. The substrate (with the sample thereon) is then fixed in an in situ analysis system so that the sample can be repeatedly detected and imaged to determine the presence of the target molecule. During in situ analysis, the sample can be repeatedly detected with various probes, which are configured to indicate the presence of one or more target molecules. During detection, reagents can be delivered to or extracted from the volume around the sample. Optionally or additionally, the temperature of the sample can be adjusted according to the needs of the reaction during detection. In addition, during imaging, the probe may need to be excited via, for example, one or more light sources, each of which has a predetermined wavelength emission distribution configured to excite one or more probes. In addition, during the imaging process, edge illumination can be provided for various imaging purposes, such as boundary detection of the sample and / or determination of the focal plane of the imaging objective. The motion of the sample should be minimized to allow accurate image processing, such as image registration and / or image stitching. Therefore, there is a need for methods, systems and devices for connecting a sample to an in situ analysis system, thereby fixing the sample for imaging, providing a volume for detecting reagents, and providing edge illumination of the sample.
[0014] FIG. 1A to FIG. 1I The sample interface module (SIM) 100 is shown in an open configuration. Figure 1A As shown, SIM 100 includes a carrier body 101 and a cover 102 having an aperture 103 and a latch 104 .
[0015] like Figure 1A1, the cover 102 is in an open configuration. The SIM 100 further includes a latch 105 configured to be coupled to a latch 104 of the cover 102. In various embodiments, the latch 105 is coupled to the stage body 101. The SIM 100 further includes a cam plate 106 disposed on the stage body 101. In various embodiments, the cover 102 is hingedly coupled to the cam plate 106 at a first end and has a latch 104 on a second end. In various embodiments, the cover 102 is hingedly coupled to the stage body 101. The cam plate 106 includes an X cam 107 and a Y cam 108, the X cam being configured to provide an X-direction force on a sample device (e.g., a cartridge), and the Y cam being configured to provide a Y-direction force on the sample device. The X cam 107 and the Y cam 108 are rotatably coupled to the cam plate 106 so that each of the cams 107, 108 rotates about an axis perpendicular to an XY plane defined by the X direction and the Y direction. In various embodiments, the X cam 107 and / or the Y cam 108 can be spring loaded. In various embodiments, the X cam 107 and / or the Y cam 108 can include a soft material (e.g., a rubber cap) to reduce the concentrated point force on the sample device. The SIM 100 also includes a cam pusher 109 coupled to the cover 102. In various embodiments, the cam pusher 109 is disposed within the cam plate 106. In various embodiments, the cam pusher 109 is configured to translate linearly within the cam plate 106 when the cover is opened or closed. In various embodiments, the cam pusher 109 includes one or more pins configured to rotate each cam 107, 108. For example, the cam pusher 109 includes a first pin 109a configured to rotate the X cam 107 and a second pin 109b configured to rotate the Y cam 108.
[0016] like FIG. 1A to FIG. 1I As shown, the SIM 100 also includes a sample positioning plate 110 disposed within the cam plate 106. As will be described in more detail below, the sample positioning plate 110 is coupled to a z lifter module that is configured to provide a spring force on the sample device in the z direction. The sample positioning plate 110 includes one or more raised portions that are configured to be received by an orifice in the bottom of the sample device. In various embodiments, the one or more raised portions have a shape (e.g., periphery) that is complementary to the periphery of the orifice in the bottom of the sample device. For example, the sample positioning plate 110 includes a first raised portion 110a, a second raised portion 110b, and a third raised portion 110c. The second raised portion 110b is disposed between the first raised portion 110a and the third raised portion 110c. In various embodiments, the raised portions 110a to 110c each have a sample positioning surface defined by planes that are coplanar with each other (e.g., a substantially flat surface configured to contact the sample device). In various embodiments, when the cover is in a position such as FIG. 2A to FIG. 2H In the closed configuration shown, the plane of the sample positioning surface is parallel to the plane defined by the cover 102. In various embodiments, the second raised portion 110b has a surface area greater than the surface area of the first raised portion 110a and / or the third raised portion 110c. In various embodiments, the second raised portion 110b has a volume greater than the volume of the first raised portion 110a and / or the third raised portion 110c. In various embodiments, the sample positioning plate 110 can be made of a material with high thermal conductivity. For example, the material can be a metal (e.g., stainless steel, aluminum, etc.).
[0017] In various embodiments, SIM 100 further includes one or more light sources 111. In various embodiments, one or more light sources are light emitting diodes (LEDs). In various embodiments, one or more light sources are disposed in a housing extending from cam plate 106. In various embodiments, one or more light sources 111 are positioned to direct light to raised portions 110a to 110c. In various embodiments, one or more light sources 111 are configured to provide edge lighting to a sample (e.g., a biological sample) positioned on a sample device (e.g., a box). In various embodiments, one or more light sources 111 include red light (e.g., about 620nm to about 750nm). In various embodiments, one or more light sources 111 include green light (e.g., about 475nm to about 570nm). In various embodiments, one or more light sources 111 include blue light (e.g., about 450nm to about 495nm). In various embodiments, one or more light sources 111 are configured for adjustable illumination intensity.
[0018] In various embodiments, edge illumination (e.g., via one or more LEDs) can couple light to a waveguide, such as a glass substrate on which a sample is positioned. In various embodiments, the waveguide is a separate device positioned below the glass substrate. Systems and methods for transilluminating a sample (e.g., using edge illumination) are described in PCT / US2023 / 060857, which is incorporated herein by reference in its entirety. In various embodiments, the waveguide receives photons through at least one side surface. In various embodiments, in order to promote a more uniform distribution of light emitted from the top surface of the waveguide, the bottom surface of the waveguide includes a light scattering layer. In various embodiments, the light scattering layer is a coating. In various embodiments, the light scattering layer comprises at least one metal oxide (e.g., aluminum oxide, titanium dioxide) nanoparticles dispersed in an epoxy resin matrix. In various embodiments, the nanoparticles scatter light in random directions and make the resulting illumination through the top surface of the waveguide more uniform. In various embodiments, the nanoparticles have an average diameter of about 500nm. In various embodiments, the nanoparticles have an average diameter of about 550nm. In various embodiments, the nanoparticles have an average diameter of about 600nm. In various embodiments, the nanoparticles have an average diameter of about 400nm to about 600nm. In various embodiments, the nanoparticles have an average diameter of about 500nm to about 600nm. In various embodiments, the nanoparticles have an average diameter of less than about 600nm. In various embodiments, the nanoparticles have an average diameter of less than about 500nm. In various embodiments, the waveguide includes at least one reflective layer and / or (e.g., silvered) coating on one or more sides to limit the amount of light leaking from the sides that do not receive edge illumination. In various embodiments, photons of light are received by the waveguide, scattered by the light scattering layer at the bottom, and emerge through the top of the waveguide.
[0019] In various embodiments, the cam plate 106 further comprises a Y pin 112 and an X pin 113a to 113b configured to align and / or secure the sample device when the sample device is positioned on the sample positioning plate 110. In various embodiments, the Y pin 112 provides a reaction force in response to the force applied to the sample device by the Y cam 108, thereby securing the sample device in the Y direction. In various embodiments, the X pins 113a to 113b provide a reaction force in response to the force applied to the sample device by the X cam 107, thereby securing the sample device in the X direction. In various embodiments, the cover 102 comprises one or more Z pins 114a to 114c configured to provide a Z-direction force on the sample device when the cover 102 is in a closed configuration. In various embodiments, when the cover 102 is closed and the Z pins 114a to 114c engage the sample device, the Z lifter module will provide a reaction force, thereby securing the sample device in the Z direction. In various embodiments, the Z pins 114a to 114c engage the sample device by directly contacting the glass substrate on the bottom surface and / or the top surface, thereby minimizing (e.g., preventing) bending of the glass substrate. In various embodiments, bending of the glass substrate can cause deformation during imaging. In various embodiments, the Z pins provide point contact on the top surface of the glass substrate. It should be noted that the Z pins can engage any portion of the sample device to secure the slide.
[0020] In various embodiments, the SIM 100 further comprises a control board 115 (e.g., a printed circuit board) configured to control electronic components (e.g., light source 111) of the SIM 100. In various embodiments, the SIM 100 further comprises a sensor 116. In various embodiments, the sensor comprises a photodetector. In various embodiments, the photodetector is an infrared (IR) sensor. In various embodiments, the sensor 116 is directed toward at least one of the raised portions 110a to 110c. In various embodiments, the sensor 116 is configured to detect the presence of a sample device positioned on the sample positioning plate 110. In various embodiments, the cam plate 106 comprises a sensor housing configured to accommodate the sensor 116.
[0021] like Figure 1F to Figure 1H As shown, SIM 100 also includes a sensor 120 configured to detect whether cover 102 is open or closed. In various embodiments, cover 102 may include a protrusion 121 that is detected by sensor 120 when cover 102 is open (e.g., protrusion 121 may block a signal from sensor 120). When cover 102 is closed, protrusion 121 may not be detected by sensor 120 (e.g., protrusion 121 may not block a signal from sensor 120). In various embodiments, as shown in FIG. Figure 1HAs shown, SIM 100 includes a fluid circuit having an inlet 122a and an outlet 122b, the fluid circuit being configured for thermal management of the thermoelectric module, as will be described in detail in Figure 3 Described in more detail in .
[0022] FIG. 2A to FIG. 2H SIM 100 is shown in a closed configuration with a sample device 400 secured therein. FIG. 2A to FIG. 2H As shown, the cover 102 is closed and the latch 104 is coupled to the catch 105. In various embodiments, when the cover 103 is in the closed configuration, the aperture 103 of the cover 102 forms a recess. In various embodiments, the sample device is fixed in the recess. In various embodiments, the recess is formed by at least a portion of the cover, at least a portion of the sample positioning plate 110, and / or at least a portion of the cam plate 106.
[0023] Figure 3 A cross section of the sample interface module in a closed configuration is shown. In various embodiments, the SIM 100 includes a z-lifter module, which will be referred to as 9A to 9E 12 is described in more detail. In various embodiments, the z-lifter module includes a fluid circuit having an inlet 122a, an outlet 122b, a fluid channel 124, and a pressure relief valve 125 along the channel 124. In various embodiments, the fluid circuit can flow a working fluid through to adjust the temperature (e.g., heating or cooling) of the SIM 100. In various embodiments, the pressure relief valve 125 can be configured to open when a threshold pressure is exceeded. In various embodiments, the pressure relief valve 125 can prevent backflow of the working fluid. In various embodiments, if the working fluid is released through the pressure relief valve, the fluid will activate the leak sensor 128. In various embodiments, if the detection and / or imaging reagent leaks through the sample device, the reagent can activate the leak sensor 128. When the leak sensor 128 detects a leak, the imaging process can be stopped and / or the user can be notified that a leak has occurred in the SIM 100.
[0024] In various embodiments, the SIM also includes a temperature control device 126. In various embodiments, the temperature control device 126 is one or more thermoelectric modules. In various embodiments, the temperature control device 126 is disposed between the z-lifter module and the sample positioning plate 110. In various embodiments, the temperature control device 126 contacts the sample positioning plate 110 (e.g., the bottom of the plate) under at least a portion of each raised portion 110a-110c. Figure 3As shown, the temperature control device 126 is positioned under the entire second raised portion 110b and only under a portion of the first raised portion 110a and the third raised portion 110c. In various embodiments, the temperature control device 126 is configured to provide a uniform temperature over the imaging area or imaging volume. For example, the temperature control device 126 conducts heat to each of the raised portions 110a to 110c, thereby providing a substantially uniform temperature within the hole formed by the base and the gasket within the sample device 400.
[0025] In various embodiments, the z-lifter module is coupled to the stage body 101 via one or more screws 123a, 123b. In various embodiments, the SIM 100 further includes one or more springs 127a, 127b (e.g., compression springs, wave springs, etc.) between the stage body 101 and the z-lifter module. In various embodiments, the screws 123a, 123b pass through the springs 127a, 127b. In various embodiments, the screws 123a, 123b are rotated to adjust the preload spring force on the z-lifter module. For example, tightening the screws 123a, 123b increases the preload force on the z-lifter module.
[0026] 4A to 4H A sample device 400 is shown. In various embodiments, the sample device 400 is a box. In various embodiments, the sample device 400 includes a bottom portion 401 and a top portion 402. In various embodiments, the top portion 402 has one or more snap-fit joints 403a to 403d (e.g., cantilever snap-fit joints) configured to be coupled to lugs 404a to 404d (cantilever lugs) of the bottom portion 401. In various embodiments, the bottom portion 402 may have a snap-fit joint, while the top portion has lugs. In various embodiments, the sample device 400 includes a recess 405 configured to receive the Y pin 112 of the SIM 100. In various embodiments, the sample device 400 includes recesses 406a to 406b configured to receive the X pins 113a to 113b of the SIM 100. In various embodiments, the sample device 400 includes apertures 407a to 407c configured to receive the Z pins 114a to 114c on the cover. The Z pins 114a to 114c can be configured to contact a substrate (e.g., a glass slide) positioned within (e.g., sandwiched between) the bottom portion 401 and the top portion 402 in the gap 413. When a substrate (not shown) is positioned within the sample device 400, a hole 408 is formed between the substrate and the gasket 700, which FIG. 7A to FIG. 7G408. In various embodiments, the sample device 400 includes a recessed portion 410 configured to receive the Y cam 108. In various embodiments, the sample device 400 includes a recessed portion 411 configured to receive the X cam 107. In various embodiments, the recessed portions 410, 411 can include a soft material (e.g., a silicone insert, a rubber insert, etc.) to prevent concentrated point forces from the cam that may damage the sample device 400. Along the periphery of the hole 408, the top portion 402 includes a ridge 409 that is configured to secure a gasket (not shown) therein, thereby forming a seal between the base of the sample device 400 and the top portion 402.
[0027] In various embodiments, the sample device 400 includes orifices 412a to 412c configured to receive raised portions 110a to 110c of the sample positioning plate 110. As shown, for example, orifices 412a and 412c can be on either side of orifice 412b. In various embodiments, the shape of the periphery of orifices 412a to 412c is complementary to the shape of the periphery of the corresponding raised portions 110a to 110c. In various embodiments, orifices 412a to 412c are slightly larger than raised portions 110a to 110c to allow for receiving raised portions 110a to 110c.
[0028] FIG. 5A to FIG. 5H A carrier 500 for a sample interface module 100a, 100b is shown. FIG. 5A to FIG. 5H As shown, the carrier 500 includes a base 501, a cover 502, an optical wetting consumable (OWC) 503 and a waste container 507 subassembly (hereinafter referred to as FIG. 10A to FIG. 10C ), vent cover 504, and controller 505 (eg, a printed circuit board).
[0029] FIG. 6A to FIG. 6C A carrier 500 for a sample interface module 100a, 100b is shown (without a top cover). In various embodiments, the carrier 500 includes a leak sensor 506 configured to detect fluid that may leak from a waste container 507 and / or the SIM 100a, 100b. In various embodiments, the carrier 500 includes an OWC sensor 508 (e.g., a OWC sensor 508 configured to detect the presence of an OWC 503). FIG. 6A to FIG. 6C shown).
[0030] FIG. 7A to FIG. 7G A gasket 700 is shown for use with the sample device 400. FIG. 7A to FIG. 7GAs shown, the gasket 700 includes a substantially flat surface defined between a first perimeter 701a and a second perimeter 701b. In various embodiments, the gasket 700 includes a tapered portion 702 between the second perimeter 701b and the third perimeter 701c. In various embodiments, the tapered portion 702 has a constant taper. In various embodiments, the tapered portion 702 has a variable taper (e.g., a curved taper). In various embodiments, the first perimeter 701a has a first width, the second perimeter 701b has a second width less than the first width, and the third perimeter 701c has a third width less than the second width. Figure 7G A cross section of a gasket 700 is shown, wherein the gasket 700 includes a substantially flat upper portion of height h1 (e.g., thickness). In various embodiments, the upper portion includes a gap 703. In various embodiments, the gasket 700 includes one or more vertical ribs 704 disposed within the gap 703. In various embodiments, the tapered portion 702 tapers over a height h2 and has an angle θ relative to a horizontal axis. In various embodiments, the angle θ corresponds to (e.g., is equal to) an angle outside the objective lens to optimize the travel distance of the objective lens, thereby maximizing the possible imaging area within the box.
[0031] FIG. 7H shows a cross section of an exemplary gasket device 710 for sample device 400 according to various embodiments. Gasket 710 may include a substantially flat surface defined between first perimeter 711a and second perimeter 711b. In various embodiments, gasket 710 includes a tapered portion 712 between second perimeter 711b and third perimeter 711c. In various embodiments, tapered portion 712 has a constant taper. In various embodiments, tapered portion 712 has a variable taper (e.g., a curved taper). In various embodiments, first perimeter 711a has a first width, second perimeter 711b has a second width less than the first width, and third perimeter 711c has a third width less than the second width. First perimeter 711a, second perimeter 711b, tapered portion 712, and third perimeter 711c together form upper portion 713, which merges with lower portion 715 around base portion 717.
[0032] For example, as shown in FIG. 7H , the upper portion 713 and the lower portion 715 together form a gap 719. FIG. 7H also shows that the lower portion 715 may include a fourth perimeter 721a having a first width, a fifth perimeter 721b having a second width, and a tapered portion 722. The tapered portion 722 may have a constant taper. In various embodiments, the tapered portion 722 may have a variable taper (e.g., a curved taper). In various embodiments, the slope (or angle θ relative to the horizontal axis) of the tapered portion 722 is the same or substantially similar to the tapered portion 712. Similarly, in various embodiments, the lower portion 715 may be coplanar with the upper portion 713.
[0033] FIG. 7H also shows that the upper portion 713 may further include an O-ring 723. The O-ring 723 may be configured to extend from an upper surface 725 of the upper portion 713. The O-ring may be disposed along any portion of the surface 725. For example, Figure 4H The O-ring 723 is shown positioned closer to the first perimeter 711a than the second perimeter 711b. The O-ring 723 can be configured to extend from the upper surface 725 and along the entire or substantially the entire perimeter of the gasket 700.
[0034] Figure 8 A leakage sensor 800 of a sample interface module is shown. In various embodiments, the leakage sensor 800 comprises a conductive material configured to output a predetermined voltage when a liquid contacts its surface. For example, the conductive material may include a conductive layer of an integrated circuit having one or more electrodes exposed to air and configured to detect the presence of a liquid on the surface of the contact conductive layer. In various embodiments, the leakage sensor 800 is formed as a thin film sensor. In various embodiments, the leakage sensor 800 is formed as a printed circuit board. In various embodiments, the leakage sensor 800 includes one or more serpentine conductors extending along the surface of the leakage sensor 800. In various embodiments, one or more serpentine conductors extend from one end of the leakage sensor 800 to the opposite end of the leakage sensor 800 so that the conductor extends over substantially the entire surface of the leakage sensor 800. In various embodiments, as described above, the leakage sensor 800 is positioned between the stage body and the z lifter module. In various embodiments, the leakage sensor 800 may include one or more openings 801a to 801c to allow a fixed element to pass therethrough. For example, screws connecting the stage body to the z-lifter module can pass through openings 801a - 801b. In various embodiments, the leak sensor includes a connection 802 for electrical communication with a controller.
[0035] 9A to 9E A riser and leveling subassembly 900 is shown. Fig.9AAs shown, the lift and leveling subassembly 900 includes a z-lift module 901 coupled to the sample positioning plate 110. FIG. 1A to FIG. 1I As described, the sample positioning plate 110 includes raised portions 110a to 110c, which are configured to be received by an orifice of a sample device (e.g., a box). In various embodiments, at least a portion (e.g., all) of the surface of each raised portion 110a to 110c contacts a slide disposed in the sample device. In various embodiments, the z lifter module 901 is coupled to the stage body via one or more screws 123a, 123b. In various embodiments, one or more springs (e.g., compression springs, wave springs, etc.) are disposed between the z lifter module 901 and the stage body, thereby providing a spring reaction force on the z lifter module 901 when the z lifter module 901 is depressed. As described above, the thermal fluid circuit has an inlet 122a and an outlet 122b.
[0036] In various embodiments, the z-lifter module 901 is coupled to the sample positioning plate 110 via one or more screws. FIG. 9C to FIG. 9E As shown, the z-lift module 901 is coupled to the sample positioning plate 110 via four screws 903a-903d, which are generally positioned near the four corners of the lift and leveling subassembly 900. In various embodiments, the screws 903a-903d can be configured to level the sample positioning plate 110 during assembly of the sample interface module 100. In various embodiments, the manufacturer can level the sample positioning plate during manufacturing so that the end user (e.g., customer) does not have to level the sample positioning plate 110. In various embodiments, the horizontal sample positioning surface comprises a substantially flat surface, wherein the plane defined by the flat surface is coplanar with the horizontal plane. Fig. 9C As shown, the z-lift module 901 also includes a pressure relief valve 125 for a thermal fluid circuit within the z-lift module 901. In various embodiments, the sample positioning plate 110 can be leveled by adjusting (e.g., rotating clockwise or counterclockwise) one or more screws 903a-903d until the sample positioning plate 110 is substantially flat when installed.
[0037] FIG. 10A to FIG. 10C An optical wetting consumable and waste container subassembly 1000 is shown. Fig. 10A and Fig. 10CAs shown, subassembly 1000 includes an optical wetting consumable 1001 disposed in a tray 1002. In various embodiments, tray 1002 includes one or more orifices 1003a to 1003c. In various embodiments, orifices 1003a to 1003c can be configured to receive one or more waste liquids, thereby collecting the waste liquids in a waste container 1004. In various embodiments, orifices 1003a to 1003c can be formed in any suitable shape, such as a circular orifice 1003b or a slot-shaped orifice 1003a, 1003c. In various embodiments, as Fig. 10B As shown, the subassembly includes a sensor 1005 configured to detect the presence of the tray 1002. In various embodiments, the sensor 1005 is an optical sensor. In various embodiments, the subassembly 1000 includes a sensor 1006 configured to detect the mass of the optical wetting consumable 1001. In various embodiments, the sensor 1006 is a load sensor.
Claims
1. A component comprising: Carrier body; A cam plate, the cam plate being arranged on the stage body; a sample positioning plate having a sample positioning surface configured to receive a sample device, wherein the sample positioning surface includes a first raised portion, a second raised portion, and a third raised portion, wherein the second raised portion is disposed between the first raised portion and the third raised portion, wherein the first raised portion, the second raised portion, and the third raised portion are configured to contact the sample device; a lifter module disposed within the stage body, wherein the lifter module is coupled to the sample positioning plate and the stage body; a cover configured to be coupled to the cam plate, wherein the cover includes an aperture, wherein the cover has a coupled configuration and a non-coupled configuration such that when in the coupled configuration, a recess is formed by at least the cover and the sample positioning plate; as well as One or more light sources are disposed in the cam plate, wherein the one or more light sources are configured to direct light within the recess.
2. The assembly of claim 1, wherein each raised portion includes a substantially flat seating surface.
3. The assembly of claim 2 wherein said seating surfaces are coplanar.
4. An assembly as claimed in claim 2 or claim 3, wherein each seating surface is parallel to the plane of the cover when the cover is in the closed configuration.
5. The assembly of any one of claims 2 to 4, wherein the seating surface of the second raised portion has a surface area greater than a surface area of the seating surface of the first raised portion.
6. The assembly of any one of claims 2 to 5, wherein the seating surface of the second raised portion has a surface area greater than a surface area of the seating surface of the third raised portion.
7. The assembly of any one of claims 2 to 6, wherein the second raised portion has a volume greater than a volume of the first raised portion.
8. The assembly of any one of claims 2 to 7, wherein the second raised portion has a volume greater than a volume of the third raised portion.
9. The assembly of any one of claims 2 to 8, wherein the sample positioning plate is configured to be thermally coupled to the sample device.
10. The assembly of any one of claims 2 to 9, further comprising a temperature control device coupled to the sample positioning plate.
11. The assembly of claim 10, wherein the temperature control device is disposed between the sample positioning plate and the riser module.
12. An assembly as claimed in claim 10 or claim 11, wherein the temperature control device comprises one or more thermoelectric modules.
13. An assembly as claimed in any one of claims 10 to 12, wherein the temperature control device is configured to provide a substantially uniform temperature across an imaging area of the sample arrangement.
14. A component as described in any one of claims 1 to 13, wherein the cam plate includes a light source housing extending therefrom, wherein the one or more light sources are disposed within the light source housing, wherein the light source housing includes an opening directed toward the recessed portion, and wherein the one or more light sources are configured to direct light toward the sample device.
15. The assembly of any one of claims 1 to 14, wherein the one or more light sources comprise one or more light emitting diodes (LEDs).
16. The assembly of any one of claims 1 to 15, wherein the one or more light sources include one or more red light sources.
17. The assembly of any one of claims 1 to 16, wherein the one or more light sources comprise one or more green light sources.
18. The assembly of any one of claims 1 to 17, wherein the one or more light sources include one or more blue light sources.
19. An assembly as claimed in any one of claims 1 to 18, wherein the one or more light sources are configured for adjustable intensity.
20. The assembly of any one of claims 1 to 19, wherein the cover extends from a first end to a second end, wherein the cover is rotatably coupled to the cam plate via a hinge at the first end.
21. The assembly of claim 20, wherein the cover further comprises a latch at the second end, wherein the carrier body further comprises a catch, wherein the latch is configured to releasably couple to the catch when the cover is in the coupled configuration.
22. An assembly as claimed in any one of claims 1 to 21, wherein the recess is further formed by at least a portion of the cam plate.
23. The assembly of any one of claims 20 to 22, further comprising a cam pusher operably coupled to the hinge, wherein the cam pusher is configured to translate when the hinge is actuated.
24. The assembly of claim 23, wherein said cam pusher translates within said cam plate.
25. The assembly of claim 23 or claim 24 further comprising one or more cams rotatably coupled to the cam plate, wherein the sample positioning plate defines a plane, wherein each cam is operably coupled to the cam pusher and is configured to rotate about an axis perpendicular to the plane.
26. The assembly of claim 25, wherein the plane is defined by an x-direction and a y-direction, wherein at least one of the one or more cams is configured to provide a force on the sample device in the x-direction.
27. The assembly of claim 25 or 26, wherein at least one of the one or more cams is configured to provide a force on the sample device in the y-direction.
28. The assembly of any one of claims 1 to 27, wherein the cam plate comprises one or more pins configured to limit movement of the sample device in at least one of the x-direction and the y-direction.
29. The assembly of any one of claims 1 to 28, wherein the cover comprises one or more pins configured to limit movement of the sample device in a z-direction, wherein the z-direction is perpendicular to the sample positioning surface.
30. The assembly of any one of claims 1 to 29, further comprising at least one spring operably coupling the lifter module to the stage body.
31. The assembly of any one of claims 1 to 30, wherein the riser module includes a fluid circuit therein.
32. An assembly as claimed in any one of claims 1 to 31, wherein the raised portion is complementary to an aperture in the sample device.
33. The assembly of any one of claims 1 to 32, further comprising a leak detector.
34. The assembly of claim 33, wherein the leak detector comprises a conductive leak detector configured to output a predetermined voltage when in contact with a liquid.
35. An assembly as claimed in claim 33 or 34, wherein the leak detector is disposed between the carrier body and the riser module.
36. The assembly of any one of claims 1 to 35, further comprising a sensor configured to detect the presence of the sample device when the sample device is positioned on the sample positioning plate.
37. The assembly of claim 36, wherein the sensor comprises a photodetector.
38. The assembly of claim 37, wherein the photodetector comprises an infrared sensor.
39. An assembly as claimed in any one of claims 36 to 38, wherein the sensor is disposed within the cam plate.
40. The assembly of any one of claims 1 to 39, further comprising at least one screw coupling the sample positioning plate to the lifter module, wherein the at least one screw is configured to adjust the plane of the sample positioning plate.
41. The assembly of claim 40, wherein the at least one screw is configured to level the sample positioning plate.
42. The assembly of claim 40 or claim 41, wherein the at least one screw comprises four screws.
43. The assembly of any one of claims 1 to 42, wherein the sample device comprises a box.
44. The assembly of claim 43, wherein the sample device comprises a glass slide disposed in the box.
45. The assembly of claim 44, wherein the slide includes a biological sample disposed thereon.
46. A method, It includes: Providing an assembly as claimed in any one of claims 1 to 45; positioning a sample device on the sample positioning plate so that each of the first raised portion, the second raised portion, and the third raised portion engages the sample device; The cover is coupled to the stage body to secure the sample device in the recess.
47. The method of claim 46, further comprising a slide disposed within the sample device, wherein positioning the sample device comprises contacting the slide with the first raised portion, the second raised portion, and the third raised portion.
48. The method of claim 46 or claim 47, further comprising energizing the one or more light sources.
49. The method of claim 48, wherein energizing the one or more light sources comprises energizing a red light source, a green light source, and / or a blue light source.
50. The method of claim 48 or claim 49, further comprising adjusting the intensity of the one or more light sources.
51. The method of any one of claims 46 to 50, further comprising regulating the temperature of the sample positioning plate.
52. The method of claim 51, wherein regulating the temperature comprises providing a substantially uniform temperature to an imaging region of the sample device.
53. The method of any one of claims 46 to 52, further comprising detecting the sample device after positioning on the sample positioning surface.
54. The method of any one of claims 46 to 53, further comprising adjusting the pitch, yaw and / or roll of the sample positioning plate.
55. The method of any one of claims 46 to 54, further comprising detecting the presence of liquid within the carrier body.
56. An apparatus comprising: a body comprising a bottom portion and a top portion, wherein the bottom portion is releasably coupled to the top portion, wherein when the bottom portion is coupled to the top portion, a gap is formed between the bottom portion and the top portion, wherein the gap is configured to receive a sample substrate; wherein the top portion includes a well configured to receive a sample; wherein the bottom portion comprises a first aperture, a second aperture and a third aperture, wherein the second aperture is disposed between the first aperture and the second aperture, wherein the body comprises at least two x-pin recesses on a first side, at least one y-pin recess on a second side perpendicular to the first side, at least one x-cam recess on a third side parallel to the first side, and at least one y-cam recess on a fourth side parallel to the second side, Wherein the top portion comprises at least one z-pin aperture.
57. The device of claim 56, wherein the area of the second orifice is greater than the area of the first orifice and the area of the third orifice.
58. A device as claimed in claim 56 or claim 57, wherein the sample substrate is a glass slide.
59. The device of any one of claims 56 to 58, wherein the top portion or the bottom portion comprises one or more tabs.
60. The device of any one of claims 56 to 59, wherein the top portion or the bottom portion comprises one or more lugs configured to releasably couple to the one or more tabs.
61. The device of any one of claims 56 to 60, further comprising a gasket disposed within the aperture, wherein the gasket extends around an inner surface of the aperture.
62. The device of claim 61, wherein the gasket comprises an angled surface.
63. The device of claim 62, wherein the angled surface tapers from a first width to a second width that is less than the first width.
64. An apparatus as claimed in claim 63 or claim 64, wherein the angle of the angled surface measured relative to the plane of the sample substrate is substantially the same as the angle of the objective lens, thereby increasing the imaging area of the objective lens.
65. The device of any one of claims 61 to 64, wherein the gasket is configured to form a seal between the sample substrate and the body.
66. A gasket comprising an inner portion having an angled surface.
67. The gasket of claim 66, wherein the angled surface tapers from a first width to a second width that is less than the first width.