WO2021112855A1 - Substrate stages with corner ribs - Google Patents

Substrate stages with corner ribs Download PDF

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Publication number
WO2021112855A1
WO2021112855A1 PCT/US2019/064704 US2019064704W WO2021112855A1 WO 2021112855 A1 WO2021112855 A1 WO 2021112855A1 US 2019064704 W US2019064704 W US 2019064704W WO 2021112855 A1 WO2021112855 A1 WO 2021112855A1
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WO
WIPO (PCT)
Prior art keywords
substrate
substrate stage
comer
fluid
rib
Prior art date
Application number
PCT/US2019/064704
Other languages
French (fr)
Other versions
WO2021112855A9 (en
Inventor
Vignesh KANNAN
Dennis R. Esterberg
Original Assignee
Hewlett-Packard Development Company, L.P.
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 Hewlett-Packard Development Company, L.P. filed Critical Hewlett-Packard Development Company, L.P.
Priority to PCT/US2019/064704 priority Critical patent/WO2021112855A1/en
Publication of WO2021112855A1 publication Critical patent/WO2021112855A1/en
Publication of WO2021112855A9 publication Critical patent/WO2021112855A9/en

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Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00Supporting devices; Holding devices
    • B01L9/52Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
    • B01L9/523Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips for multisample carriers, e.g. used for microtitration plates
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00Supporting devices; Holding devices
    • B01L9/52Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
    • 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
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/023Adapting objects or devices to another adapted for different sizes of tubes, tips or container
    • 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
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/025Align devices or objects to ensure defined positions relative to each other
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0609Holders integrated in container to position an object
    • 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
    • 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
    • B01L2300/0829Multi-well plates; Microtitration plates

Definitions

  • An assay is a process used in laboratory medicine, pharmacology, analytical chemistry, environmental biology, and molecular biology to assess or measure the presence, amount, or functional activity of a sample.
  • the sample may be a drug, a genomic sample, a proteomic sample, a biochemical substance, a cell in an organism, an organic sample, or other inorganic and organic chemical samples.
  • an assay is carried out by dispensing small amounts of fluid into multiple wells of a well-plate. The fluid in these wells can then be processed and analyzed. Such assays can be used to enable drug discovery as well as facilitate genomic and proteomic research.
  • FIG. 1 is a block diagram of a substrate stage with comer ribs, according to an example of the principles described herein.
  • Fig. 2 is an isometric view of the substrate stage with corner ribs, according to an example of the principles described herein.
  • Fig. 3 is an isometric view of the substrate stage with corner ribs with a well-plate disposed thereon, according to an example of the principles described herein.
  • Fig. 4 is a top view of the substrate stage with comer ribs, according to an example of the principles described herein.
  • Fig. 5 is a top view of the substrate stage with corner ribs with a well-plate disposed thereon, according to an example of the principles described herein.
  • Fig. 6 is a cross-sectional view of the substrate stage with comer ribs, according to an example of the principles described herein.
  • Fig. 7 is an exploded view of the substrate stage with corner ribs and a fixture substrate, according to an example of the principles described herein.
  • Fig. 8 is an isometric view of the substrate stage with corner ribs with a fixture substrate disposed thereon, according to an example of the principles described herein.
  • FIG. 9 is an isometric view of a fluid ejection system with a substrate stage with corner ribs, according to an example of the principles described herein.
  • An assay is a process used in laboratory medicine, pharmacology, analytical chemistry, environmental biology, and molecular biology to assess or measure the presence, amount, or functional activity of a sample.
  • the sample may be a drug, a genomic sample, a proteomic sample, a biochemical substance, a cell in an organism, an organic sample, or other inorganic and organic chemical samples.
  • an assay is carried out by dispensing small amounts of fluid into multiple wells of a well-plate. The fluid in these wells can then be processed and analyzed. Such assays can be used to enable drug discovery as well as facilitate genomic and proteomic research.
  • Such assays have been performed manually. That is, a user fills fluid into a single channel pipette, or a multi-channel pipette, and manually disperses a prescribed amount of fluid from the pipette into various wells of a well-plate.
  • the present specification describes the digital dispensing of fluid to replace manual dispensing methods.
  • high precision digital fluid ejection devices which may include fluidic dies, are used.
  • a fluidic die includes a number of nozzles. Each nozzle holds a small volume of fluid and an actuator expels that fluid through an opening. In operation, the fluidic dies dispense the fluid onto a substrate, such as into wells of a well-plate positioned below the fluidic dies. A fluid ejection system holds and aligns the fluidic dies and the substrate relative to one another.
  • the substrate may be disposed on a substrate stage which is movable such that the fluidic die may eject fluid into different locations, such as wells, of the target surface.
  • the nozzles may eject fluid into a first set of wells and the substrate stage may then move such that fluid may be ejected into a different set of wells.
  • the fluid ejection system may properly position the substrate with respect to the substrate by moving either the fluidic dies or the substrate.
  • the present specification describes a fluid ejection system, which may be a benchtop research instrument, that is used for dispensing picoliter quantities of target fluids into well-plates, or other substrates.
  • the fluid ejection system may move the substrate relative to the fluidic die. Ensuring proper alignment between the fluidic die and the substrate ensures the accuracy and reliability of certain operations carried out by the fluid ejection system. For example, if a biological experiment is to study a reaction between a dispensed compound and different reagents placed in different wells of a well-plate, misalignment of the well-plate could invalidate the experiment.
  • the well-plate may be misaligned relative to the fluidic die. This mis-alignment will impact the function of the experiment for which the well-plate is being used.
  • a substrate that is manually mounted on a substrate stage can be misaligned due to human-error causing the fluid being dispensed to fall into an incorrect location or point. This can invalidate an experiment and result in wasteful use of test fluids, which may be expensive. The invalidation of test results reduces the efficacy of assays and can increase the cost, complexity, and time to generate accurate results.
  • the present specification also handles the substrate to ensure proper alignment of the fluid ejection devices and the target surface, whether that target surface be wells of the well-plate, or any other target surface.
  • the present specification describes a substrate stage for ensuring proper alignment between a fluid ejection device and the substrate upon which fluid is to be ejected. Specifically, the present specification describes a substrate stage that has raised ribs at the corners of a region of the stage to receive the substrate.
  • the substrate stage is an injection molded part that is mounted and fastened on a linear motor assembly of a fluid ejection system.
  • the substrate stage includes a substrate enclosure and a clamp.
  • the clamp is used to bias, locate, and hold the substrate against the raised ribs that surround the substrate enclosure.
  • the fluid ejection system may a benchtop device.
  • the fluid ejection system may be positioned on top of a table in a laboratory.
  • the fluid ejection system may include a conveyance system. In this example, the conveyance system may move the substrate stage with the associated substrate to different locations within a room wherein different operations may be performed at the different stages.
  • the raised ribs cause the substrate to tilt if misaligned.
  • This tilting is a visual indication to a user of the misalignment. Accordingly, if a user attempts to clamp a substrate in a misaligned position in either of the x- and y- directions, the bottom of the substrate will rest on top of the raised ribs, thus providing visual indication to the user that the well-plate is not planar and not within an area of the stage where it will be aligned with the fluidic die.
  • the raised ribs also prevent the substrate from moving in the z- direction. That is, during movement of the substrate stage during fluid ejection, instrument vibrations may disturb the substrate, compounds on the substrate, and may result in misalignment between the target surfaces and the fluid ejection device.
  • the raised ribs, or portions thereof include tapered surfaces which interact with the substrate to maintain it in a particular position and prevent the vibration of the substrate.
  • the present systems and devices can be used to deposit fluid on other target surfaces such as microscope slides, matrix assisted laser desorption/ionization (MALDI) plates, petri dishes, and microfluidic chips among other substrates or surfaces.
  • the substrate may include a fixture that fits into the comer ribs and the clamp and retains the target surface.
  • the substrate stage includes a substrate region disposed on a surface, the substrate region to receive a substrate.
  • the substrate stage also includes at least two comer ribs at corners of the substrate region, each comer rib rising up from the surface.
  • a notch is formed in a leg of each comer rib that is parallel with a leg of another corner rib.
  • the substrate stage also includes a clamp to hold the substrate against the at least two comer ribs.
  • the substrate stage includes a substrate region disposed on a surface, the substrate region to receive a substrate.
  • the substrate stage also includes at least two comer ribs at corners of the substrate region, each comer rib rising up from the surface.
  • a leg of a first comer rib is colinear with a leg of a second corner rib and a length of each leg of each comer rib is at least one-third of a respective side of the substrate region.
  • the substrate stage includes a notch formed in a leg of each comer rib that is parallel with a leg of another corner rib.
  • the substrate stage also includes a manually-operated clamp to hold the well-plate against the at least two corner ribs.
  • the present specification also describes a fluid ejection system that includes a base and a substrate stage movably coupled to the base to hold a substrate during fluid deposition.
  • the substrate stage includes 1 ) a substrate region disposed on a surface, the substrate region to receive the substrate, 2) at least two corner ribs at corners of the substrate region, each comer rib rising up from the surface, 3) a notch formed in a leg of each corner rib that is parallel with a leg of another comer rib; and 4) a clamp to hold a substrate against the at least two comer ribs.
  • the fluid ejection system also includes a frame vertical to the substrate stage to hold a fluid ejection device. The fluid ejection device ejects fluid onto the substrate.
  • the present specification describes a fluid ejection system that increases a throughput for low volume dispensing applications and allows dispensing of fluids into multiple wells of a well-plate.
  • the fluid ejection system includes multiple fluid ejection devices arranged in an array, which fluid ejection devices use a fluid actuator to eject a small amount of fluid into multiple wells of a well-plate.
  • Such a system can operate to eject low, for example in the picoliter range, volumes of fluid into one or multiple wells at a time.
  • the present specification describes a substrate stage that ensures that the substrate aligns with overhead fluid ejection devices to ensure fluid ejected from the fluid ejection devices lands in specific predetermined locations to ensure the accuracy of any fluid ejection operation.
  • fluid die refers to a component of a fluid ejection system that ejects fluid and includes a number of nozzles.
  • nozzle refers to an individual component of a fluidic die that ejects fluid.
  • the nozzle includes at least an ejection chamber to hold an amount of fluid and an opening through which the fluid is ejected.
  • the ejection subassembly includes an actuator disposed within the ejection chamber.
  • fluid ejection device refers to a fluidic die and a reservoir associated with the fluidic die.
  • Such systems and methods 1) align a substrate in a predetermined location such that fluid is deposited onto the substrate as intended; 2) provide a visual indication of substrate misalignment; 3) ensure the accuracy and reliability of fluidic operations; 4) maintain the substrate in place in an x- and y- direction during fluid ejection operations; 5) prevent the substrate from moving in the z- direction during experimentation; and 6) can be handled by automated robotic equipment.
  • the systems and methods disclosed herein may address other matters and deficiencies in a number of technical areas.
  • Fig. 1 is a block diagram of a substrate stage (100) with comer ribs (104), according to an example of the principles described herein.
  • a fluid ejection system ejects fluid onto a surface.
  • the surface may be a well-plate with a number of wells, and the fluid may be deposited into the individual wells of the well-plate.
  • the fluid ejection system may be implemented in a laboratory and may eject biological fluid.
  • the fluid dispensed by the fluid ejection system may be of a variety of types and may be used for a variety of applications.
  • the biological fluid may include solvent or aqueous-based pharmaceutical compounds, as well as aqueous-based biomolecules including proteins, enzymes, lipids, antibiotics, mastermix, primer, DNA samples, cells, or blood components, all with or without additives, such as surfactants or glycerol.
  • a fluid ejection controller passes control signals and routes them to fluid ejection devices of the fluid ejection system.
  • the present systems and devices can be used to deposit fluid on other substrates or surfaces such as microscope slides, matrix assisted laser desorption/ionization (MALDI) plates, and microfluidic chips among other substrates or surfaces.
  • the substrate may be at least one of a well-plate and a fixture substrate to retain a target surface on which a fluid is to be deposited.
  • Figs. 3, 5, and 6 depict examples where the substrate is a well-plate.
  • Figs. 7 and 8 depict examples where the substrate is a fixture for differently- sized target surface.
  • the substrate that is placed on the substrate stage may be a fixture that retains the target surface.
  • Such a fluid ejection systems may be used in titration processes, compound secondary screening, enzyme profiling, and polymerase chain reactions (PCR), among other chemical and biochemical reactions.
  • Other examples of applications where such a fluid ejection system is used include dose-response titrations, polymerase chain reaction (PCR) miniaturization, microarray printing, drug-drug combination testing, drug repurposing, drug metabolism and pharmacokinetics (DMPK) dispensing and a wide variety of other life science dispensing. While particular reference is made to particular applications, the fluid ejection system can be used in a variety of applications. [0041] As described above, such fluid ejection systems are used to deposit fluid onto a substrate.
  • the substrate may be any material on which fluid may be dispensed.
  • the substrate may be a well-plate with a number of wells in an array. Such a well-plate may be between approximately 4 and 50 millimeters thick. While specific reference is made to a particular substrate thickness.
  • the fluid ejection system may be used with substrates having a wide variety of thicknesses.
  • the substrate may be any surface on which fluid may be deposited.
  • the substrate stage (100) of the present disclosure ensures proper alignment.
  • the substrate stage (100) includes certain structural components that prevent misalignment between the substrate and the fluidic die.
  • the substrate stage (100) refers to a component that retains the substrate.
  • the substrate stage (100) includes a substrate region (102) disposed on a surface, which substrate region is to receive a substrate that is to receive a fluid. That is, the substrate stage (100) may be formed of a material such as polymer plastic that has a planar surface.
  • a substrate region (102) refers to a portion of this polymer plastic surface where a substrate is to be placed to receive fluid from a fluid ejection device.
  • the substrate stage (100) includes a mounting system to retain the substrate in a fixed position relative to the substrate stage (100). In this manner, the substrate is secured to the substrate stage (100) and remains in place during movement of the substrate stage (100) relative to the base of the fluid ejection system when fluid from the fluid ejection device is dispensed onto the various portions of the substrate (100).
  • this mounting system includes at least two corner ribs (104) at corners of the substrate region (102).
  • Each corner rib (104) rises up from the surface.
  • the comer ribs (104) are vertical protrusions from the surface of the substrate stage (100).
  • the substrate is pushed against these vertical protrusions to ensure proper positioning.
  • these corner ribs (104) prevent misalignment. If a substrate is aligned improperly in either direction, it will rest on the ribs (104) and the substrate will be inclined with respect to the substrate stage (100) thus providing a visual indication to a user of the misalignment.
  • the corner ribs (104) are formed of two legs joined perpendicularly to one another in the same plane.
  • a notch (106) may be formed in a corner rib (104) leg that is parallel with a leg of another comer rib (104). That is, the comer ribs (104) may each have a leg that is colinear with another leg. The other leg of the corner ribs (104) are therefore parallel with one another and on opposite sides of the substrate region (102).
  • These parallel legs may have notches (106) formed therein.
  • the notches (106) facilitate handling by an automated robotic arm. That is, a robotic arm may have fingers that can grasp substrates such as well-plates. These notches (106) may be sized such that the fingers of the robotic assembly can grasp the sides of the substrate to move it into and out of the substrate stage (100).
  • the substrate stage (100) also includes a clamp (108) to hold the substrate against the at least two comer ribs (104). That is, as described above, the substrate is pressed against the two comer ribs (104) to ensure proper alignment.
  • the clamp (108) provides the force that pushes the substrate against the at least two comer ribs (104).
  • the clamp (108) may be manually operated. That is, the clamp (108) may have a pivot point and a user may grasp an arm of the clamp (108) to rotate it into a position where it is acting to push the substrate against the corner ribs (104).
  • the substrate stage (100), via the comer ribs (104) ensures proper alignment of the substrate with the overhead fluid ejection devices and also provides a visual indication to a user when the substrate is misaligned.
  • Fig. 2 is an isometric view of the substrate stage (100) with corner ribs (104), according to an example of the principles described herein.
  • the substrate stage (100) includes a substrate region (102) which is sized to receive a particular substrate, such as a well-plate having a number of fluid wells into which fluid, such as biological fluid, is to be ejected.
  • Fig. 2 also depicts the at least two corner ribs (104-1 , 104-2) formed around two comers of the substrate region (102) and that rise from the surface of the substrate stage (100). As described above, these corner ribs (104) cause the well-plate to tilt if misaligned in the x- and/or y- directions, thus visually indicating to a user the misalignment and non-planarity of the well-plate during installation.
  • each corner rib (104) is defined by its legs.
  • a leg of a first comer rib (104-1) is colinear with a leg of a second comer rib (104-2).
  • the at least two comer ribs (104) may be formed at adjacent corners of the substrate region (102).
  • a length of each leg of each comer rib (104) may have a length that is at least one-third a length of a respective side of the substrate region (102).
  • the colinear legs and the parallel legs of respective comer ribs (104) may extend at least a third of the way around corresponding sides of the substrate region (102). Doing so provides a greater surface area against which the substrate may be aligned, thus further ensuring proper alignment.
  • the greater surface area provides enough resistance against the force exerted by the clamp (108). That is, were a smaller size leg to be used, the force of the clamp (108) pushing the substrate against the legs may cause the legs to break, thus rendering the substrate stage (100) inoperable to ensure and maintain alignment throughout the fluid ejection operation.
  • Fig. 2 also depicts the notches (106-1 , 106-2) that are formed in a leg of each corner rib (104) that is parallel with a leg of another corner rib (104). That is, the non-colinear legs, that is the legs of the ribs (104) that are opposite one another and on opposite sides of the substrate region (102), may have notches (106) therein. The notches (106) allow a 2-fingered automated robot to insert and/or remove the substrate from the substrate stage (100).
  • Fig. 2 also depicts the clamp (108), which may be manually-operated, which holds the well- plate or other substrate against the at least two corner ribs (104). As depicted in Fig.
  • the clamp (108) is disposed along an edge of the substrate region (102) that is opposite and parallel to collinear legs of the first comer rib (104-1) and the second corner rib (104-2). That is, the force exerted by the clamp (108) may push the substrate towards the colinear legs.
  • the substrate stage (100) includes additional components to further align the substrate relative to the substrate stage (100) and to maintain the substrate in position relative to the substrate stage (100).
  • the substrate stage (102) may have a number of platforms (212) rising away from the surface.
  • a single platform (212) is indicated with a reference number.
  • the platforms (212) reduce the surface friction between the well-plate and the substrate stage (100). That is, both the substrate stage (100) and the substrate may be formed of a polymer plastic material. If the surface friction between these two components is too great, the substrate may not readily slide along the substrate stage (100) to be properly positioned and aligned.
  • the surface friction can impact substrate insertion in other ways.
  • the surface friction may cause the substrate to vibrate as it moves into position. This vibration may disturb the samples in the well-plates and in some cases may cause the contents to spill over, thus altering and potentially invalidating test results.
  • the platforms (212) being raised from the surface, reduce the contact area between the substrate and the substrate stage (100). That is, rather than having the entire underside of the substrate contact the substrate stage (100), just a portion of the underside contacts the platforms (212), thus reducing overall surface friction.
  • the platforms (212) are disposed around a border of the substrate region (102) with at least one platform being adjacent a comer rib.
  • the platforms (212) may be adjacent tapered sections (210) of the comer ribs (104) as well as other raised elements around the substrate region (102).
  • the substrate stage (100) also includes a raised stop (214) along an edge of the substrate region (102) that is opposite and parallel to the colinear legs of the at least two corner ribs (104-1 , 104-2).
  • This raised stop (214) further prevents misalignment of the substrate when positioned in the substrate region (102).
  • a platform (212) may be disposed adjacent this raised stop (214).
  • an interior surface of each corner rib (104) may include a tapered section (210) which tapers towards the surface. That is, the cross-sectional width of the portion of the rib (104) may be wider at the top as compared to a width where the rib (104) meets the substrate stage (100) surface. Such a taper prevents motion of the substrate in the vertical direction.
  • a cross-sectional view of the tapered section (210) is provided in connection with Fig. 6.
  • the tapered section (210) extends for a portion of a length of the interior surface.
  • each tapered section (210-1, 210-2, 210-3, 210-4) does not extend a whole length of the respective leg.
  • the tapered sections (210) may provide too great a force to overcome during insertion of the substrate.
  • the wider width of the tapered sections (210) at the top of the comer ribs (104) creates a slightly narrower opening for the substrate to be inserted into, thus a certain amount of force is used to push the substrate into the substrate region (102).
  • the force may be too great to overcome, or may be great enough that in overcoming this force, the well-plate or, the substrate stage (100) itself may be come damaged or the test may be disrupted.
  • Fig. 3 is an isometric view of the substrate stage (100) with corner ribs (104) with a well-plate (316) disposed thereon, according to an example of the principles described herein.
  • the substrate stage (100) is to hold a substrate, which in the example depicted in Fig. 3 is a well-plate (316).
  • the well-plate (316) sits between raised surfaces on opposite sides of the substrate stage (100). That is, the parallel legs of the comer ribs (104) are disposed on either side of the well-plate (316) in one direction, and the collinear legs of the corner ribs (104) and the raised stop (214) are disposed on either side of the well-plate (316) in a second direction.
  • the comer ribs (104) are shorter than a height of the substrate.
  • the raised stop (214) may as well be shorter than a height of the substrate. Were the comer ribs (104) and raised stop (214) higher than the substrate, it may impact the movement of the substrate and substrate stage (100) underneath the fluid ejection device.
  • Fig. 3 also clearly depicts the notches (106) and illustrates how a robotic arm could grasp the well-plate (316) out from the substrate region (Fig.
  • Fig. 4 is a top view of the substrate stage (100) with comer ribs (104-1 , 104-2), according to an example of the principles described herein. Specifically, Fig. 4 depicts the comer ribs (104) with their associated notches (106) as well as the raised stop (214).
  • Fig. 4 clearly depicts the tapered sections (210-1 , 210-2, 210-3, 210-4) and how they extend for just a portion of the length of the respective comer rib (104) legs.
  • the longer the tapered section (210) the greater the force to be overcome to place the substrate in the substrate region (102). Accordingly, by just being a portion of the length of the respective comer rib (104) leg length, a user can more easily overcome the force and insert the substrate into the substrate region (102).
  • Fig. 4 also clearly depicts the relative position of the different legs of the comer ribs (104) as well as the raised stop (214).
  • the parallel legs of the corner ribs (104) prevent misalignment in the x- direction, (left-to-right in Fig. 4).
  • the substrate would be tilted, thus visually indicating to the user that the substrate is misaligned.
  • the substrate is too far right, an edge of the substrate will rest on the second comer rib (104-2), while the other edge of the substrate is on a floor of the substrate region (102).
  • the tilt of the substrate visually indicates the substrate misalignment.
  • the collinear legs of the corner ribs (104) and the raised stop (214) prevent misalignment in the y- direction, (top-to-bottom in Fig. 4). For example, if the substrate is too far towards the top of the page, an edge of the substrate will rest on the collinear legs of both the first corner rib (104-1) and the second comer rib (104-2), while the other edge of the substrate is on a floor of the substrate region (102). In this example, the substrate would be tilted, thus visually indicating to the user that the substrate is misaligned.
  • the present substrate stage (100) provides a physically perceptible misalignment of the substrate.
  • Fig. 4 also clearly depicts the platforms (212). As depicted in Fig. 4, the surface area of the platform is less than the surface area of the substrate region (102) floor. Accordingly, a substrate slides across these platforms (212) much easier than across the floor of the substrate region (102) due to a lower contact area and contact friction. As described above, this reduced contact area and friction enhances the positioning of the substrate on the substrate stage (100).
  • Fig. 5 is a top view of the substrate stage (100) with comer ribs (104) with a well-plate (316) disposed thereon, according to an example of the principles described herein.
  • the well-plate (316) is properly seated in the substrate region (Fig. 1, 102) as defined by its being placed between the corner ribs (104) and the raised stop (214).
  • the substrate (316) is in a particular location relative the substrate stage (100).
  • the fluid ejection system may calibrate motion of the substrate stage (100) such that fluid can be deterministically ejected into particular wells of the well-plate (316).
  • Fig. 6 is a cross-sectional view of the substrate stage (100) with comer ribs (214), according to an example of the principles described herein. Specifically, Fig. 6 is a cross-sectional view of the substrate stage (100) and well-plate (316) taken along the line A-A from Fig. 5. Fig. 6 clearly depicts the well-plate (316) as it is placed on top of the substrate stage (100). Fig. 6 also clearly depicts the tapered section (212) of the comer ribs (Fig. 1 , 104). In some examples, the tapered section (212) has an angle of less than 90 degrees relative to the surface of the substrate stage (100). This angle is indicated by the angle symbol in Fig. 6.
  • this section prevents the well-plate (316), or other substrate, from moving in the vertical direction which may otherwise result due to vibrations caused by movement of the substrate stage (100) and/or the movement of the well-plate (316) relative to the substrate stage (100).
  • Fig. 6 also clearly depicts a platform (214) on which the well-plate (316) rests during operation. Note that in Fig. 6, the elements are not necessarily drawn to scale. For example, the platform (214) may be 100 microns thick.
  • Fig. 7 is an exploded view of the substrate stage (100) with comer ribs (104) and a fixture substrate (718), according to an example of the principles described herein.
  • Fig. 7 clearly depicts the substrate region (102) which is sized to receive a particular substrate, such as a well-plate having a number of fluid wells into which fluid, such as biological fluid, is to be ejected.
  • the target surface may be smaller than the substrate for which the substrate region (102) is sized.
  • the target surface may be a microscope slide, which is smaller than a well-plate.
  • the substrate may be a fixture substrate (718) which is sized to fit within the substrate region (102), but that retains a differently-sized target surface.
  • the fixture substrate (718) may include a locking mechanism, such as clips to hold the target surface against the fixture substrate (718) during fluid deposition.
  • Fig. 7 also depicts the at least two corner ribs (104-1 , 104-2) that rise from the surface of the substrate stage (100) and the notches (106-1 , 106- 2) formed therein.
  • Fig. 7 also depicts the clamp (108), platforms (212), tapered sections (210) and raised stop (214).
  • clamp 108
  • platforms 212
  • tapered sections 2
  • raised stop 214
  • Fig. 8 is an isometric view of the substrate stage (100) with comer ribs (104-1 , 104-2) with a fixture substrate (718) disposed thereon, according to an example of the principles described herein.
  • the substrate stage (100) is to hold a substrate, which in the example depicted in Fig. 7 is a fixture substrate (718) on which a target surface is positioned and retained.
  • the fixture substrate (718) sits between raised surfaces on opposite sides of the substrate stage (100).
  • Fig. 7 also clearly depicts the notches (106) and illustrates how a robotic arm could grasp the fixture substrate (718) out from the substrate region (Fig. 1 , 102). That is, the fingers of a robotic arm may drop down from above the fixture substrate (718) and may grasp the fixture substrate (718) through the notches (106).
  • Fig. 9 is an isometric view of a fluid ejection system (920) with a substrate stage (100) with corner ribs (214), according to an example of the principles described herein.
  • the fluid ejection system (920) may dispense fluid into wells of a well-plate (Fig. 3, 316) or onto another surface and the fluid that may be ejected may be of various types.
  • Such fluid ejection systems (920) may be used in titration processes, compound secondary screening, enzyme profiling, and polymerase chain reactions (PCR), among other chemical and biochemical reactions.
  • the fluid ejection system (920) includes a base (922) to hold a substrate stage (100).
  • the substrate stage (100) is movably coupled to the base (922) to hold a substrate stationary relative to the substrate stage (100) during fluid deposition, although the substrate stage (100) is movable relative to the base (922) during fluid deposition.
  • the substrate stage (100) moves as instructed by a processing device in order to place the substrate into a desired position underneath the fluid ejection devices retained in the frame (924).
  • the substrate stage (100) includes a mount to retain the substrate in a fixed position relative to the substrate stage (100). In this manner, the substrate is secured to the substrate stage (100) and remains in place during movement of the substrate stage (100) relative to the base (922) when fluid from the fluid ejection device is dispensed onto the various portions of the substrate.
  • the substrate stage (100) includes a substrate region (Fig. 1 , 102) to receive the substrate and at least two corner ribs (Fig. 1 , 104) at comers of the substrate region (Fig. 1, 102), which corner ribs (Fig. 1 , 104) rise from the surface of the substrate stage (100).
  • Notches (Fig. 1 , 106) formed in legs of each of the comer ribs (Fig. 1 , 104) that are parallel with other legs of the comer ribs (Fig. 1 , 104) keep the substrate in place during fluid deposition.
  • the substrate stage (100) also includes a clamp (Fig. 1, 108) to hold the substrate against the at least two comer ribs (Fig. 1 , 104).
  • the substrate stage (100) is removable from the base (922) and moveable relative to the base during fluid deposition. That is, it may be the case that a substrate stage (100) is to be replaced with another, or different substrate stage (100).
  • the fluid ejection system (920) also includes a frame (924) that is vertical to the substrate stage (100).
  • the frame (924) holds a fluid ejection device which ejects fluid onto the substrate.
  • the fluid ejection device is removable and/or disposable. That is, a user may manually, or via robotic device, insert a cassette that includes a variety of fluid ejection devices.
  • a processor coupled to the fluid ejection system (920) activates an ejector to eject fluid from the fluid ejection device onto a location of the substrate. This same processor may operate to move the substrate stage (100) such that fluid may be deposited in other locations on the substrate.
  • the fluid ejection devices operate to dispense picoliter quantities of a target fluid into the wells.
  • Each fluid ejection device may include includes a reservoir to hold the fluid to be ejected.
  • the reservoir is open, or exposed, so that a user, either manually or via a machine- operated multi-channel pipette, can fill the reservoirs with the target fluid.
  • the fluidic dies may be discrete MEMSs (Micro-Electro-Mechanical Systems) where each fluidic die dispenses drops of between approximately 1.0 picoliters and 500 picoliters.
  • Each fluid ejection device also includes a fluidic die.
  • the fluidic die is fluidly coupled to the reservoir. That is, during operation, fluid from the reservoir is passed to a fluidic die where it is ejected onto a surface.
  • the fluidic die includes a number of components to eject fluid.
  • the fluidic die rely on inkjet technology to eject fluid therefrom.
  • Such a fluid ejection system (920), by using inkjet components such as ejection chambers, openings, and actuators disposed within the micro-fluidic ejection chambers, enables low- volume dispensing of fluids such as those used in life science and clinical applications.
  • Such systems and methods 1) align a substrate in a predetermined location such that fluid is deposited onto the substrate as intended; 2) provide a visual indication of substrate misalignment; 3) ensure the accuracy and reliability of fluidic operations; 4) maintain the substrate in place in an x- and y- direction during fluid ejection operations; 5) prevent the substrate from moving in the z- direction during experimentation; and 6) can be handled by automated robotic equipment.
  • the systems and methods disclosed herein may address other matters and deficiencies in a number of technical areas.

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Abstract

In one example in accordance with the present disclosure, a substrate stage is described. The substrate stage includes a substrate region disposed on a surface. The substrate region receives a substrate that is to receive a fluid. At least two corner ribs rise up from the surface at corners of the substrate region. Notches are formed in a leg of each corner rib that is parallel with a leg of another corner rib. The substrate stage also includes a clamp to hold the substrate against the at least two corner ribs.

Description

SUBSTRATE STAGES WITH CORNER RIBS
BACKGROUND
[0001] An assay is a process used in laboratory medicine, pharmacology, analytical chemistry, environmental biology, and molecular biology to assess or measure the presence, amount, or functional activity of a sample. The sample may be a drug, a genomic sample, a proteomic sample, a biochemical substance, a cell in an organism, an organic sample, or other inorganic and organic chemical samples. In general, an assay is carried out by dispensing small amounts of fluid into multiple wells of a well-plate. The fluid in these wells can then be processed and analyzed. Such assays can be used to enable drug discovery as well as facilitate genomic and proteomic research.
BRIEF DESCRIPTION OF THE DRAWINGS
[0002] The accompanying drawings illustrate various examples of the principles described herein and are part of the specification. The illustrated examples are given merely for illustration, and do not limit the scope of the claims.
[0003] Fig. 1 is a block diagram of a substrate stage with comer ribs, according to an example of the principles described herein.
[0004] Fig. 2 is an isometric view of the substrate stage with corner ribs, according to an example of the principles described herein.
[0005] Fig. 3 is an isometric view of the substrate stage with corner ribs with a well-plate disposed thereon, according to an example of the principles described herein. [0006] Fig. 4 is a top view of the substrate stage with comer ribs, according to an example of the principles described herein.
[0007] Fig. 5 is a top view of the substrate stage with corner ribs with a well-plate disposed thereon, according to an example of the principles described herein.
[0008] Fig. 6 is a cross-sectional view of the substrate stage with comer ribs, according to an example of the principles described herein.
[0009] Fig. 7 is an exploded view of the substrate stage with corner ribs and a fixture substrate, according to an example of the principles described herein.
[0010] Fig. 8 is an isometric view of the substrate stage with corner ribs with a fixture substrate disposed thereon, according to an example of the principles described herein.
[0011] Fig. 9 is an isometric view of a fluid ejection system with a substrate stage with corner ribs, according to an example of the principles described herein.
[0012] Throughout the drawings, identical reference numbers designate similar, but not necessarily identical, elements. The figures are not necessarily to scale, and the size of some parts may be exaggerated to more clearly illustrate the example shown. Moreover, the drawings provide examples and/or implementations consistent with the description; however, the description is not limited to the examples and/or implementations provided in the drawings.
DETAILED DESCRIPTION
[0013] An assay is a process used in laboratory medicine, pharmacology, analytical chemistry, environmental biology, and molecular biology to assess or measure the presence, amount, or functional activity of a sample. The sample may be a drug, a genomic sample, a proteomic sample, a biochemical substance, a cell in an organism, an organic sample, or other inorganic and organic chemical samples. In general, an assay is carried out by dispensing small amounts of fluid into multiple wells of a well-plate. The fluid in these wells can then be processed and analyzed. Such assays can be used to enable drug discovery as well as facilitate genomic and proteomic research.
[0014] Such assays have been performed manually. That is, a user fills fluid into a single channel pipette, or a multi-channel pipette, and manually disperses a prescribed amount of fluid from the pipette into various wells of a well-plate.
As this process is done by hand, it is tedious, complex, and inefficient.
Moreover, it is prone to error as a user may misalign the pipette with the wells of the well-plate and/or may dispense an incorrect amount of fluid. Still further, such manual deposition of fluid may be incapable of dispensing low volumes of fluid, for example in the picoliter range.
[0015] While specific reference is made to user error regarding misalignment of a pipette relative to wells of a well-plate, such misalignment may occur regarding the dispensing of a fluid onto any target surface.
[0016] Accordingly, the present specification describes the digital dispensing of fluid to replace manual dispensing methods. In these examples, high precision digital fluid ejection devices, which may include fluidic dies, are used.
A fluidic die includes a number of nozzles. Each nozzle holds a small volume of fluid and an actuator expels that fluid through an opening. In operation, the fluidic dies dispense the fluid onto a substrate, such as into wells of a well-plate positioned below the fluidic dies. A fluid ejection system holds and aligns the fluidic dies and the substrate relative to one another.
[0017] For example, the substrate may be disposed on a substrate stage which is movable such that the fluidic die may eject fluid into different locations, such as wells, of the target surface. For example, the nozzles may eject fluid into a first set of wells and the substrate stage may then move such that fluid may be ejected into a different set of wells. In other words, the fluid ejection system may properly position the substrate with respect to the substrate by moving either the fluidic dies or the substrate. Accordingly, the present specification describes a fluid ejection system, which may be a benchtop research instrument, that is used for dispensing picoliter quantities of target fluids into well-plates, or other substrates. [0018] As described above, the fluid ejection system may move the substrate relative to the fluidic die. Ensuring proper alignment between the fluidic die and the substrate ensures the accuracy and reliability of certain operations carried out by the fluid ejection system. For example, if a biological experiment is to study a reaction between a dispensed compound and different reagents placed in different wells of a well-plate, misalignment of the well-plate could invalidate the experiment.
[0019] In examples of manually loading, the well-plate may be misaligned relative to the fluidic die. This mis-alignment will impact the function of the experiment for which the well-plate is being used.
[0020] Put another way, a substrate that is manually mounted on a substrate stage can be misaligned due to human-error causing the fluid being dispensed to fall into an incorrect location or point. This can invalidate an experiment and result in wasteful use of test fluids, which may be expensive. The invalidation of test results reduces the efficacy of assays and can increase the cost, complexity, and time to generate accurate results.
[0021] Accordingly, in addition to describing a fluid ejection system that automatically ejects predetermined amounts of fluid onto a substrate, the present specification also handles the substrate to ensure proper alignment of the fluid ejection devices and the target surface, whether that target surface be wells of the well-plate, or any other target surface.
[0022] Accordingly, the present specification describes a substrate stage for ensuring proper alignment between a fluid ejection device and the substrate upon which fluid is to be ejected. Specifically, the present specification describes a substrate stage that has raised ribs at the corners of a region of the stage to receive the substrate.
[0023] In some examples, the substrate stage is an injection molded part that is mounted and fastened on a linear motor assembly of a fluid ejection system. The substrate stage includes a substrate enclosure and a clamp. The clamp is used to bias, locate, and hold the substrate against the raised ribs that surround the substrate enclosure. [0024] In some examples, the fluid ejection system may a benchtop device. For example, the fluid ejection system may be positioned on top of a table in a laboratory. In another example, the fluid ejection system may include a conveyance system. In this example, the conveyance system may move the substrate stage with the associated substrate to different locations within a room wherein different operations may be performed at the different stages.
[0025] In general, the raised ribs cause the substrate to tilt if misaligned.
This tilting is a visual indication to a user of the misalignment. Accordingly, if a user attempts to clamp a substrate in a misaligned position in either of the x- and y- directions, the bottom of the substrate will rest on top of the raised ribs, thus providing visual indication to the user that the well-plate is not planar and not within an area of the stage where it will be aligned with the fluidic die.
[0026] In some examples, the raised ribs also prevent the substrate from moving in the z- direction. That is, during movement of the substrate stage during fluid ejection, instrument vibrations may disturb the substrate, compounds on the substrate, and may result in misalignment between the target surfaces and the fluid ejection device. In some examples, the raised ribs, or portions thereof, include tapered surfaces which interact with the substrate to maintain it in a particular position and prevent the vibration of the substrate. [0027] Note that throughout the specification, while specific reference is made to deposition of fluid into wells of a well-plate, the present systems and devices can be used to deposit fluid on other target surfaces such as microscope slides, matrix assisted laser desorption/ionization (MALDI) plates, petri dishes, and microfluidic chips among other substrates or surfaces. In the later examples, the substrate may include a fixture that fits into the comer ribs and the clamp and retains the target surface.
[0028] Specifically, the specification describes a substrate stage. The substrate stage includes a substrate region disposed on a surface, the substrate region to receive a substrate. The substrate stage also includes at least two comer ribs at corners of the substrate region, each comer rib rising up from the surface. A notch is formed in a leg of each comer rib that is parallel with a leg of another corner rib. The substrate stage also includes a clamp to hold the substrate against the at least two comer ribs.
[0029] In another example, the substrate stage includes a substrate region disposed on a surface, the substrate region to receive a substrate. The substrate stage also includes at least two comer ribs at corners of the substrate region, each comer rib rising up from the surface. In this example, a leg of a first comer rib is colinear with a leg of a second corner rib and a length of each leg of each comer rib is at least one-third of a respective side of the substrate region. In this example, the substrate stage includes a notch formed in a leg of each comer rib that is parallel with a leg of another corner rib. The substrate stage also includes a manually-operated clamp to hold the well-plate against the at least two corner ribs.
[0030] The present specification also describes a fluid ejection system that includes a base and a substrate stage movably coupled to the base to hold a substrate during fluid deposition. In this example, the substrate stage includes 1 ) a substrate region disposed on a surface, the substrate region to receive the substrate, 2) at least two corner ribs at corners of the substrate region, each comer rib rising up from the surface, 3) a notch formed in a leg of each corner rib that is parallel with a leg of another comer rib; and 4) a clamp to hold a substrate against the at least two comer ribs. The fluid ejection system also includes a frame vertical to the substrate stage to hold a fluid ejection device. The fluid ejection device ejects fluid onto the substrate.
[0031] As such, the present specification describes a fluid ejection system that increases a throughput for low volume dispensing applications and allows dispensing of fluids into multiple wells of a well-plate. Specifically, the fluid ejection system includes multiple fluid ejection devices arranged in an array, which fluid ejection devices use a fluid actuator to eject a small amount of fluid into multiple wells of a well-plate. Such a system can operate to eject low, for example in the picoliter range, volumes of fluid into one or multiple wells at a time.
[0032] Still further, the present specification describes a substrate stage that ensures that the substrate aligns with overhead fluid ejection devices to ensure fluid ejected from the fluid ejection devices lands in specific predetermined locations to ensure the accuracy of any fluid ejection operation.
[0033] As used in the present specification and in the appended claims, the term “fluidic die” refers to a component of a fluid ejection system that ejects fluid and includes a number of nozzles.
[0034] Accordingly, as used in the present specification and in the appended claims, the term “nozzle” refers to an individual component of a fluidic die that ejects fluid. The nozzle includes at least an ejection chamber to hold an amount of fluid and an opening through which the fluid is ejected. In some examples, the ejection subassembly includes an actuator disposed within the ejection chamber.
[0035] Accordingly, as used in the present specification and in the appended claims, the term “fluid ejection device” refers to a fluidic die and a reservoir associated with the fluidic die.
[0036] Such systems and methods 1) align a substrate in a predetermined location such that fluid is deposited onto the substrate as intended; 2) provide a visual indication of substrate misalignment; 3) ensure the accuracy and reliability of fluidic operations; 4) maintain the substrate in place in an x- and y- direction during fluid ejection operations; 5) prevent the substrate from moving in the z- direction during experimentation; and 6) can be handled by automated robotic equipment. However, it is contemplated that the systems and methods disclosed herein may address other matters and deficiencies in a number of technical areas.
[0037] Turning now to the figures, Fig. 1 is a block diagram of a substrate stage (100) with comer ribs (104), according to an example of the principles described herein. In general, a fluid ejection system ejects fluid onto a surface. As described above, the surface may be a well-plate with a number of wells, and the fluid may be deposited into the individual wells of the well-plate.
[0038] A variety of fluids may be deposited. For example, the fluid ejection system may be implemented in a laboratory and may eject biological fluid. The fluid dispensed by the fluid ejection system may be of a variety of types and may be used for a variety of applications. In some examples, the biological fluid may include solvent or aqueous-based pharmaceutical compounds, as well as aqueous-based biomolecules including proteins, enzymes, lipids, antibiotics, mastermix, primer, DNA samples, cells, or blood components, all with or without additives, such as surfactants or glycerol. To eject the fluid, a fluid ejection controller passes control signals and routes them to fluid ejection devices of the fluid ejection system.
[0039] While specific reference is made to deposition of fluid into wells of a well-plate, the present systems and devices can be used to deposit fluid on other substrates or surfaces such as microscope slides, matrix assisted laser desorption/ionization (MALDI) plates, and microfluidic chips among other substrates or surfaces. That is the substrate may be at least one of a well-plate and a fixture substrate to retain a target surface on which a fluid is to be deposited. Figs. 3, 5, and 6 depict examples where the substrate is a well-plate. Figs. 7 and 8 depict examples where the substrate is a fixture for differently- sized target surface. In this example, the substrate that is placed on the substrate stage may be a fixture that retains the target surface.
[0040] Such a fluid ejection systems may be used in titration processes, compound secondary screening, enzyme profiling, and polymerase chain reactions (PCR), among other chemical and biochemical reactions. Other examples of applications where such a fluid ejection system is used include dose-response titrations, polymerase chain reaction (PCR) miniaturization, microarray printing, drug-drug combination testing, drug repurposing, drug metabolism and pharmacokinetics (DMPK) dispensing and a wide variety of other life science dispensing. While particular reference is made to particular applications, the fluid ejection system can be used in a variety of applications. [0041] As described above, such fluid ejection systems are used to deposit fluid onto a substrate. The substrate may be any material on which fluid may be dispensed. In one example, the substrate may be a well-plate with a number of wells in an array. Such a well-plate may be between approximately 4 and 50 millimeters thick. While specific reference is made to a particular substrate thickness. The fluid ejection system may be used with substrates having a wide variety of thicknesses. Moreover, while specific reference is made to a well-plate as a specific example of a substrate, the substrate may be any surface on which fluid may be deposited.
[0042] As described above, accurate alignment of the substrate and the fluidic die of the fluid ejection system ensures accurate results. That is, incorrect test results will result if fluid is intended to be deposited into a particular well of a well-plate, but is actually deposited in another well. The substrate stage (100) of the present disclosure ensures proper alignment. Specifically, the substrate stage (100) includes certain structural components that prevent misalignment between the substrate and the fluidic die.
[0043] The substrate stage (100) refers to a component that retains the substrate. Specifically, the substrate stage (100) includes a substrate region (102) disposed on a surface, which substrate region is to receive a substrate that is to receive a fluid. That is, the substrate stage (100) may be formed of a material such as polymer plastic that has a planar surface. A substrate region (102) refers to a portion of this polymer plastic surface where a substrate is to be placed to receive fluid from a fluid ejection device.
[0044] The substrate stage (100) includes a mounting system to retain the substrate in a fixed position relative to the substrate stage (100). In this manner, the substrate is secured to the substrate stage (100) and remains in place during movement of the substrate stage (100) relative to the base of the fluid ejection system when fluid from the fluid ejection device is dispensed onto the various portions of the substrate (100).
[0045] Specifically, this mounting system includes at least two corner ribs (104) at corners of the substrate region (102). Each corner rib (104) rises up from the surface. In other words, the comer ribs (104) are vertical protrusions from the surface of the substrate stage (100). During installation of a substrate, the substrate is pushed against these vertical protrusions to ensure proper positioning. As described above, these corner ribs (104) prevent misalignment. If a substrate is aligned improperly in either direction, it will rest on the ribs (104) and the substrate will be inclined with respect to the substrate stage (100) thus providing a visual indication to a user of the misalignment. [0046] The corner ribs (104) are formed of two legs joined perpendicularly to one another in the same plane. A notch (106) may be formed in a corner rib (104) leg that is parallel with a leg of another comer rib (104). That is, the comer ribs (104) may each have a leg that is colinear with another leg. The other leg of the corner ribs (104) are therefore parallel with one another and on opposite sides of the substrate region (102). These parallel legs may have notches (106) formed therein. The notches (106) facilitate handling by an automated robotic arm. That is, a robotic arm may have fingers that can grasp substrates such as well-plates. These notches (106) may be sized such that the fingers of the robotic assembly can grasp the sides of the substrate to move it into and out of the substrate stage (100).
[0047] The substrate stage (100) also includes a clamp (108) to hold the substrate against the at least two comer ribs (104). That is, as described above, the substrate is pressed against the two comer ribs (104) to ensure proper alignment. The clamp (108) provides the force that pushes the substrate against the at least two comer ribs (104). In some examples, the clamp (108) may be manually operated. That is, the clamp (108) may have a pivot point and a user may grasp an arm of the clamp (108) to rotate it into a position where it is acting to push the substrate against the corner ribs (104).
[0048] Accordingly, the substrate stage (100), via the comer ribs (104) ensures proper alignment of the substrate with the overhead fluid ejection devices and also provides a visual indication to a user when the substrate is misaligned.
[0049] Fig. 2 is an isometric view of the substrate stage (100) with corner ribs (104), according to an example of the principles described herein. As described above, the substrate stage (100) includes a substrate region (102) which is sized to receive a particular substrate, such as a well-plate having a number of fluid wells into which fluid, such as biological fluid, is to be ejected.
Fig. 2 also depicts the at least two corner ribs (104-1 , 104-2) formed around two comers of the substrate region (102) and that rise from the surface of the substrate stage (100). As described above, these corner ribs (104) cause the well-plate to tilt if misaligned in the x- and/or y- directions, thus visually indicating to a user the misalignment and non-planarity of the well-plate during installation.
[0050] As described above, each corner rib (104) is defined by its legs.
In one particular example, a leg of a first comer rib (104-1) is colinear with a leg of a second comer rib (104-2). For example, the at least two comer ribs (104) may be formed at adjacent corners of the substrate region (102). In some examples, a length of each leg of each comer rib (104) may have a length that is at least one-third a length of a respective side of the substrate region (102). For example, the colinear legs and the parallel legs of respective comer ribs (104) may extend at least a third of the way around corresponding sides of the substrate region (102). Doing so provides a greater surface area against which the substrate may be aligned, thus further ensuring proper alignment.
Moreover, the greater surface area provides enough resistance against the force exerted by the clamp (108). That is, were a smaller size leg to be used, the force of the clamp (108) pushing the substrate against the legs may cause the legs to break, thus rendering the substrate stage (100) inoperable to ensure and maintain alignment throughout the fluid ejection operation.
[0051] Fig. 2 also depicts the notches (106-1 , 106-2) that are formed in a leg of each corner rib (104) that is parallel with a leg of another corner rib (104). That is, the non-colinear legs, that is the legs of the ribs (104) that are opposite one another and on opposite sides of the substrate region (102), may have notches (106) therein. The notches (106) allow a 2-fingered automated robot to insert and/or remove the substrate from the substrate stage (100). Fig. 2 also depicts the clamp (108), which may be manually-operated, which holds the well- plate or other substrate against the at least two corner ribs (104). As depicted in Fig. 2, in some examples, the clamp (108) is disposed along an edge of the substrate region (102) that is opposite and parallel to collinear legs of the first comer rib (104-1) and the second corner rib (104-2). That is, the force exerted by the clamp (108) may push the substrate towards the colinear legs.
[0052] In some examples, the substrate stage (100) includes additional components to further align the substrate relative to the substrate stage (100) and to maintain the substrate in position relative to the substrate stage (100). [0053] For example, the substrate stage (102) may have a number of platforms (212) rising away from the surface. For simplicity, a single platform (212) is indicated with a reference number. The platforms (212) reduce the surface friction between the well-plate and the substrate stage (100). That is, both the substrate stage (100) and the substrate may be formed of a polymer plastic material. If the surface friction between these two components is too great, the substrate may not readily slide along the substrate stage (100) to be properly positioned and aligned. Even if it does not prevent proper alignment, the surface friction can impact substrate insertion in other ways. For example, during installation, when the clamp (108) is activated, the surface friction may cause the substrate to vibrate as it moves into position. This vibration may disturb the samples in the well-plates and in some cases may cause the contents to spill over, thus altering and potentially invalidating test results. [0054] Accordingly, the platforms (212) being raised from the surface, reduce the contact area between the substrate and the substrate stage (100). That is, rather than having the entire underside of the substrate contact the substrate stage (100), just a portion of the underside contacts the platforms (212), thus reducing overall surface friction.
[0055] As depicted in Fig. 2, in some examples, the platforms (212) are disposed around a border of the substrate region (102) with at least one platform being adjacent a comer rib. The platforms (212) may be adjacent tapered sections (210) of the comer ribs (104) as well as other raised elements around the substrate region (102).
[0056] In some examples, the substrate stage (100) also includes a raised stop (214) along an edge of the substrate region (102) that is opposite and parallel to the colinear legs of the at least two corner ribs (104-1 , 104-2). This raised stop (214) further prevents misalignment of the substrate when positioned in the substrate region (102). As depicted in Fig. 2, a platform (212) may be disposed adjacent this raised stop (214).
[0057] In one example, an interior surface of each corner rib (104) may include a tapered section (210) which tapers towards the surface. That is, the cross-sectional width of the portion of the rib (104) may be wider at the top as compared to a width where the rib (104) meets the substrate stage (100) surface. Such a taper prevents motion of the substrate in the vertical direction. A cross-sectional view of the tapered section (210) is provided in connection with Fig. 6.
[0058] In some examples, the tapered section (210) extends for a portion of a length of the interior surface. In one particular example, each tapered section (210-1, 210-2, 210-3, 210-4) does not extend a whole length of the respective leg. Were the tapered sections (210) to be longer, that is the whole length of the comer rib (104) legs, it may provide too great a force to overcome during insertion of the substrate. For example, the wider width of the tapered sections (210) at the top of the comer ribs (104) creates a slightly narrower opening for the substrate to be inserted into, thus a certain amount of force is used to push the substrate into the substrate region (102). Were the tapered section (210) to extend an entire length of the comer ribs (104), the force may be too great to overcome, or may be great enough that in overcoming this force, the well-plate or, the substrate stage (100) itself may be come damaged or the test may be disrupted.
[0059] Fig. 3 is an isometric view of the substrate stage (100) with corner ribs (104) with a well-plate (316) disposed thereon, according to an example of the principles described herein. As described above, the substrate stage (100) is to hold a substrate, which in the example depicted in Fig. 3 is a well-plate (316). The well-plate (316) sits between raised surfaces on opposite sides of the substrate stage (100). That is, the parallel legs of the comer ribs (104) are disposed on either side of the well-plate (316) in one direction, and the collinear legs of the corner ribs (104) and the raised stop (214) are disposed on either side of the well-plate (316) in a second direction.
[0060] In some examples, the comer ribs (104) are shorter than a height of the substrate. The raised stop (214) may as well be shorter than a height of the substrate. Were the comer ribs (104) and raised stop (214) higher than the substrate, it may impact the movement of the substrate and substrate stage (100) underneath the fluid ejection device. [0061] Fig. 3 also clearly depicts the notches (106) and illustrates how a robotic arm could grasp the well-plate (316) out from the substrate region (Fig.
1 , 102). That is, the fingers of a robotic arm may drop down from above the well-plate (316) and may grasp the well-plate (316) through the notches (106). [0062] Fig. 4 is a top view of the substrate stage (100) with comer ribs (104-1 , 104-2), according to an example of the principles described herein. Specifically, Fig. 4 depicts the comer ribs (104) with their associated notches (106) as well as the raised stop (214).
[0063] Fig. 4 clearly depicts the tapered sections (210-1 , 210-2, 210-3, 210-4) and how they extend for just a portion of the length of the respective comer rib (104) legs. As described above, the longer the tapered section (210), the greater the force to be overcome to place the substrate in the substrate region (102). Accordingly, by just being a portion of the length of the respective comer rib (104) leg length, a user can more easily overcome the force and insert the substrate into the substrate region (102).
[0064] Fig. 4 also clearly depicts the relative position of the different legs of the comer ribs (104) as well as the raised stop (214). For example, the parallel legs of the corner ribs (104) prevent misalignment in the x- direction, (left-to-right in Fig. 4). For example, if the substrate is too far left, an edge of the substrate will rest on the first corner rib (104-1), while the other edge of the substrate is on a floor of the substrate region (102). In this example, the substrate would be tilted, thus visually indicating to the user that the substrate is misaligned. Similarly, if the substrate is too far right, an edge of the substrate will rest on the second comer rib (104-2), while the other edge of the substrate is on a floor of the substrate region (102). In this example, the tilt of the substrate visually indicates the substrate misalignment.
[0065] Similarly, the collinear legs of the corner ribs (104) and the raised stop (214) prevent misalignment in the y- direction, (top-to-bottom in Fig. 4). For example, if the substrate is too far towards the top of the page, an edge of the substrate will rest on the collinear legs of both the first corner rib (104-1) and the second comer rib (104-2), while the other edge of the substrate is on a floor of the substrate region (102). In this example, the substrate would be tilted, thus visually indicating to the user that the substrate is misaligned. Similarly, if the substrate is too far towards the bottom of the page, an edge of the substrate will rest on the raised stop (214) and the clamp (108), while the other edge of the substrate is on a floor of the substrate region (102). Again, the tilt of the substrate visually indicates the substrate misalignment. Thus, the present substrate stage (100) provides a physically perceptible misalignment of the substrate.
[0066] Fig. 4 also clearly depicts the platforms (212). As depicted in Fig. 4, the surface area of the platform is less than the surface area of the substrate region (102) floor. Accordingly, a substrate slides across these platforms (212) much easier than across the floor of the substrate region (102) due to a lower contact area and contact friction. As described above, this reduced contact area and friction enhances the positioning of the substrate on the substrate stage (100).
[0067] Fig. 5 is a top view of the substrate stage (100) with comer ribs (104) with a well-plate (316) disposed thereon, according to an example of the principles described herein. As clearly depicted in Fig. 5, the well-plate (316) is properly seated in the substrate region (Fig. 1, 102) as defined by its being placed between the corner ribs (104) and the raised stop (214). In other words, the substrate (316) is in a particular location relative the substrate stage (100). Accordingly, the fluid ejection system may calibrate motion of the substrate stage (100) such that fluid can be deterministically ejected into particular wells of the well-plate (316).
[0068] Fig. 6 is a cross-sectional view of the substrate stage (100) with comer ribs (214), according to an example of the principles described herein. Specifically, Fig. 6 is a cross-sectional view of the substrate stage (100) and well-plate (316) taken along the line A-A from Fig. 5. Fig. 6 clearly depicts the well-plate (316) as it is placed on top of the substrate stage (100). Fig. 6 also clearly depicts the tapered section (212) of the comer ribs (Fig. 1 , 104). In some examples, the tapered section (212) has an angle of less than 90 degrees relative to the surface of the substrate stage (100). This angle is indicated by the angle symbol in Fig. 6. As described above, the tapered nature of this section prevents the well-plate (316), or other substrate, from moving in the vertical direction which may otherwise result due to vibrations caused by movement of the substrate stage (100) and/or the movement of the well-plate (316) relative to the substrate stage (100).
[0069] Fig. 6 also clearly depicts a platform (214) on which the well-plate (316) rests during operation. Note that in Fig. 6, the elements are not necessarily drawn to scale. For example, the platform (214) may be 100 microns thick.
[0070] Fig. 7 is an exploded view of the substrate stage (100) with comer ribs (104) and a fixture substrate (718), according to an example of the principles described herein. Fig. 7 clearly depicts the substrate region (102) which is sized to receive a particular substrate, such as a well-plate having a number of fluid wells into which fluid, such as biological fluid, is to be ejected. However, in this example, the target surface may be smaller than the substrate for which the substrate region (102) is sized. For example, the target surface may be a microscope slide, which is smaller than a well-plate. In this example, the substrate may be a fixture substrate (718) which is sized to fit within the substrate region (102), but that retains a differently-sized target surface. In this example, the fixture substrate (718) may include a locking mechanism, such as clips to hold the target surface against the fixture substrate (718) during fluid deposition.
[0071] Fig. 7 also depicts the at least two corner ribs (104-1 , 104-2) that rise from the surface of the substrate stage (100) and the notches (106-1 , 106- 2) formed therein. Fig. 7 also depicts the clamp (108), platforms (212), tapered sections (210) and raised stop (214). For simplicity, in Fig. 7, a single instance of various components are indicated with a reference number.
[0072] Fig. 8 is an isometric view of the substrate stage (100) with comer ribs (104-1 , 104-2) with a fixture substrate (718) disposed thereon, according to an example of the principles described herein. As described above, the substrate stage (100) is to hold a substrate, which in the example depicted in Fig. 7 is a fixture substrate (718) on which a target surface is positioned and retained. The fixture substrate (718) sits between raised surfaces on opposite sides of the substrate stage (100). That is, the parallel legs of the corner ribs (104) are disposed on either side of the fixture substrate (718) in one direction, and the collinear legs of the corner ribs (104) and the raised stop (214) are disposed on either side of the fixture substrate (718) in a second direction. [0073] Fig. 7 also clearly depicts the notches (106) and illustrates how a robotic arm could grasp the fixture substrate (718) out from the substrate region (Fig. 1 , 102). That is, the fingers of a robotic arm may drop down from above the fixture substrate (718) and may grasp the fixture substrate (718) through the notches (106).
[0074] Fig. 9 is an isometric view of a fluid ejection system (920) with a substrate stage (100) with corner ribs (214), according to an example of the principles described herein. As described above, the fluid ejection system (920) may dispense fluid into wells of a well-plate (Fig. 3, 316) or onto another surface and the fluid that may be ejected may be of various types. Such fluid ejection systems (920) may be used in titration processes, compound secondary screening, enzyme profiling, and polymerase chain reactions (PCR), among other chemical and biochemical reactions.
[0075] The fluid ejection system (920) includes a base (922) to hold a substrate stage (100). The substrate stage (100) is movably coupled to the base (922) to hold a substrate stationary relative to the substrate stage (100) during fluid deposition, although the substrate stage (100) is movable relative to the base (922) during fluid deposition. The substrate stage (100) moves as instructed by a processing device in order to place the substrate into a desired position underneath the fluid ejection devices retained in the frame (924).
[0076] In some examples, the substrate stage (100) includes a mount to retain the substrate in a fixed position relative to the substrate stage (100). In this manner, the substrate is secured to the substrate stage (100) and remains in place during movement of the substrate stage (100) relative to the base (922) when fluid from the fluid ejection device is dispensed onto the various portions of the substrate.
[0077] Accordingly, the substrate stage (100) includes a substrate region (Fig. 1 , 102) to receive the substrate and at least two corner ribs (Fig. 1 , 104) at comers of the substrate region (Fig. 1, 102), which corner ribs (Fig. 1 , 104) rise from the surface of the substrate stage (100). Notches (Fig. 1 , 106) formed in legs of each of the comer ribs (Fig. 1 , 104) that are parallel with other legs of the comer ribs (Fig. 1 , 104) keep the substrate in place during fluid deposition. The substrate stage (100) also includes a clamp (Fig. 1, 108) to hold the substrate against the at least two comer ribs (Fig. 1 , 104).
[0078] In some examples, the substrate stage (100) is removable from the base (922) and moveable relative to the base during fluid deposition. That is, it may be the case that a substrate stage (100) is to be replaced with another, or different substrate stage (100).
[0079] The fluid ejection system (920) also includes a frame (924) that is vertical to the substrate stage (100). The frame (924) holds a fluid ejection device which ejects fluid onto the substrate. In some examples, the fluid ejection device is removable and/or disposable. That is, a user may manually, or via robotic device, insert a cassette that includes a variety of fluid ejection devices. In this example, a processor coupled to the fluid ejection system (920) activates an ejector to eject fluid from the fluid ejection device onto a location of the substrate. This same processor may operate to move the substrate stage (100) such that fluid may be deposited in other locations on the substrate.
[0080] In some cases, the fluid ejection devices operate to dispense picoliter quantities of a target fluid into the wells. Each fluid ejection device may include includes a reservoir to hold the fluid to be ejected. In some examples, the reservoir is open, or exposed, so that a user, either manually or via a machine- operated multi-channel pipette, can fill the reservoirs with the target fluid. The fluidic dies may be discrete MEMSs (Micro-Electro-Mechanical Systems) where each fluidic die dispenses drops of between approximately 1.0 picoliters and 500 picoliters.
[0081] Each fluid ejection device also includes a fluidic die. The fluidic die is fluidly coupled to the reservoir. That is, during operation, fluid from the reservoir is passed to a fluidic die where it is ejected onto a surface. The fluidic die includes a number of components to eject fluid. In some examples, the fluidic die rely on inkjet technology to eject fluid therefrom. Such a fluid ejection system (920), by using inkjet components such as ejection chambers, openings, and actuators disposed within the micro-fluidic ejection chambers, enables low- volume dispensing of fluids such as those used in life science and clinical applications.
[0082] Such systems and methods 1) align a substrate in a predetermined location such that fluid is deposited onto the substrate as intended; 2) provide a visual indication of substrate misalignment; 3) ensure the accuracy and reliability of fluidic operations; 4) maintain the substrate in place in an x- and y- direction during fluid ejection operations; 5) prevent the substrate from moving in the z- direction during experimentation; and 6) can be handled by automated robotic equipment. However, it is contemplated that the systems and methods disclosed herein may address other matters and deficiencies in a number of technical areas.

Claims

CLAIMS What is claimed is:
1. A substrate stage, comprising: a substrate region disposed on a surface, the substrate region to receive a substrate; at least two corner ribs at corners of the substrate region, each comer rib rising up from the surface; a notch formed in a leg of each comer rib that is parallel with a leg of another comer rib; and a clamp to hold the substrate against the at least two corner ribs.
2. The substrate stage of claim 1 , wherein a leg of a first comer rib is colinear with a leg of a second comer rib.
3. The substrate stage of claim 2, wherein the clamp is disposed along an edge of the substrate region that is opposite and parallel to colinear legs of the first comer rib and the second comer rib.
4. The substrate stage of claim 1 , wherein an interior surface of each comer rib comprises a tapered section which tapers towards the surface.
5. The substrate stage of claim 4, wherein the tapered section extends for a portion of a length of the interior surface.
6. The substrate stage of claim 4, wherein the tapered section has an angle less than 90 degrees relative to the surface of the substrate stage.
7. The substrate stage of claim 1 , further comprising a number of platforms rising away from the surface.
8. The substrate stage of claim 7, wherein: the platforms are disposed around a border of the substrate region; and at least one platform is adjacent a comer rib.
9. A substrate stage, comprising: a substrate region disposed on a surface, the substrate region to receive a substrate; at least two corner ribs at corners of the substrate region, each comer rib rising up from the surface, wherein: a leg of a first comer rib is colinear with a leg of a second corner rib; and a length of each leg of each comer rib is at least one-third a length of a respective side of the substrate region; a notch formed in a leg of each comer rib that is parallel with a leg of another comer rib; and a manually-operated clamp to hold the substrate against the at least two corner ribs.
10. The substrate stage of claim 9, further comprising a raised stop along an edge of the substrate region that is opposite and parallel to the colinear legs of the at least two corner ribs.
11. The substrate stage of claim 9, wherein the at least two corner ribs are formed at adjacent comers of the substrate region.
12. A fluid ejection system, comprising: a base; a substrate stage movably coupled to the base to hold a substrate during fluid deposition, wherein the substrate stage comprises: a substrate region disposed on a surface, the substrate region to receive the substrate; at least two corner ribs at corners of the substrate region, each comer rib rising up from the surface; a notch formed in a leg of each comer rib that is parallel with a leg of another comer rib; and a clamp to hold a substrate against the at least two comer ribs; and a frame vertical to the substrate stage to hold a fluid ejection device, the fluid ejection device to eject fluid onto the substrate.
13. The fluid ejection system of claim 12, wherein the corner ribs are shorter than a height of the substrate.
14. The fluid ejection system of claim 12, wherein the substrate stage: is removable from the base; and is moveable relative to the base during fluid deposition.
15. The fluid ejection system of claim 12, further comprising the substrate which is at least one of: a well-plate; and a fixture substrate to retain a target surface on which a fluid is to be deposited.
PCT/US2019/064704 2019-12-05 2019-12-05 Substrate stages with corner ribs WO2021112855A1 (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0542422A1 (en) * 1991-11-12 1993-05-19 General Atomics Multi-well microtiter plate
US8105783B2 (en) * 2007-07-13 2012-01-31 Handylab, Inc. Microfluidic cartridge
US9519000B2 (en) * 2010-07-23 2016-12-13 Beckman Coulter, Inc. Reagent cartridge
WO2017161056A1 (en) * 2016-03-15 2017-09-21 Abbott Laboratories Sample preparation cartridges and methods for using same

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0542422A1 (en) * 1991-11-12 1993-05-19 General Atomics Multi-well microtiter plate
US8105783B2 (en) * 2007-07-13 2012-01-31 Handylab, Inc. Microfluidic cartridge
US9519000B2 (en) * 2010-07-23 2016-12-13 Beckman Coulter, Inc. Reagent cartridge
WO2017161056A1 (en) * 2016-03-15 2017-09-21 Abbott Laboratories Sample preparation cartridges and methods for using same

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