US20130234053A1 - Diagnostic instrument and flow process - Google Patents

Diagnostic instrument and flow process Download PDF

Info

Publication number
US20130234053A1
US20130234053A1 US13/696,277 US201113696277A US2013234053A1 US 20130234053 A1 US20130234053 A1 US 20130234053A1 US 201113696277 A US201113696277 A US 201113696277A US 2013234053 A1 US2013234053 A1 US 2013234053A1
Authority
US
United States
Prior art keywords
flow cytometer
filter
aperture
probe
cross
Prior art date
Legal status (The legal status 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 status listed.)
Abandoned
Application number
US13/696,277
Other languages
English (en)
Inventor
Richard A Thomas
Michael A Thomas
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Beckman Coulter Inc
Blue Ocean Biomedical LLC
Original Assignee
Beckman Coulter Biomedical LLC
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 Beckman Coulter Biomedical LLC filed Critical Beckman Coulter Biomedical LLC
Priority to US13/696,277 priority Critical patent/US20130234053A1/en
Assigned to BECKMAN COULTER BIOMEDICAL, LLC reassignment BECKMAN COULTER BIOMEDICAL, LLC ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: BLUE OCEAN BIOMEDICAL, LLC
Assigned to BECKMAN COULTER, INC. reassignment BECKMAN COULTER, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: BLUE OCEAN BIOMEDICAL, LLC
Assigned to BECKMAN COULTER BIOMEDICAL, LLC. reassignment BECKMAN COULTER BIOMEDICAL, LLC. CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNEE (RECEIVING PARTY) PREVIOUSLY RECORDED ON REEL 029543 FRAME 0601. ASSIGNOR(S) HEREBY CONFIRMS THE CORRECTION OF THE ASSIGNEE FROM BECKMAN COULTER, INC. TO BECKMAN COULTER BIOMEDICAL, LLC.. Assignors: BLUE OCEAN BIOMEDICAL, LLC
Assigned to BLUE OCEAN BIOMEDICAL, LLC reassignment BLUE OCEAN BIOMEDICAL, LLC ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: THOMAS, MICHAEL A., THOMAS, RICHARD A.
Publication of US20130234053A1 publication Critical patent/US20130234053A1/en
Assigned to BECKMAN COULTER, INC. reassignment BECKMAN COULTER, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: BECKMAN COULTER BIOMEDICAL, LLC
Abandoned legal-status Critical Current

Links

Images

Classifications

    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16B—DEVICES FOR FASTENING OR SECURING CONSTRUCTIONAL ELEMENTS OR MACHINE PARTS TOGETHER, e.g. NAILS, BOLTS, CIRCLIPS, CLAMPS, CLIPS OR WEDGES; JOINTS OR JOINTING
    • F16B7/00—Connections of rods or tubes, e.g. of non-circular section, mutually, including resilient connections
    • F16B7/18—Connections of rods or tubes, e.g. of non-circular section, mutually, including resilient connections using screw-thread elements
    • F16B7/182—Connections of rods or tubes, e.g. of non-circular section, mutually, including resilient connections using screw-thread elements for coaxial connections of two rods or tubes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N21/05—Flow-through cuvettes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N35/1011—Control of the position or alignment of the transfer device
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1079—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices with means for piercing stoppers or septums
    • H—ELECTRICITY
    • H02—GENERATION; CONVERSION OR DISTRIBUTION OF ELECTRIC POWER
    • H02K—DYNAMO-ELECTRIC MACHINES
    • H02K7/00—Arrangements for handling mechanical energy structurally associated with dynamo-electric machines, e.g. structural association with mechanical driving motors or auxiliary dynamo-electric machines
    • H02K7/003—Couplings; Details of shafts
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry

Definitions

  • the present invention relates generally to a diagnostic system, and more specifically to a diagnostic system and instrument that uses a probe.
  • the diagnostic instrument may be coupled to a probe washing system and method, and may also be coupled to other components through the coupling system disclosed.
  • the instrument may also have a fluid level measuring system and a probe stall detection system.
  • a flow cytometer directs a flow of particles through a sensing zone where the particles can be excited by a beam of light.
  • the beam of light causes the particles to fluoresce and/or scatter light, and the emitted light is separated by filters into portions of the electromagnetic (EM) spectrum.
  • EM electromagnetic
  • the proposed system relates to a fluorescence-based, cellular analysis system capable of running standardized immune monitoring panels.
  • the proposed system combines automated specimen/sample preparation (e.g. blood samples, bone marrow, serum, urine, synovial, spinal, peritoneal, plural, or any other type of fluid or sample) and analysis in a single, compact instrument.
  • the single instrument provides improved accuracy, minimal clinician interaction (and therefore minimal clinician training), faster processing time, and processing options ranging from single-sample to a plurality of samples processing.
  • such a plurality of samples may be processed and analyzed continuously.
  • a specimen autoloader can be provided for moderate-to-high volume laboratories.
  • clinicians can load sample tube(s) into the system (either via autoloader or single-sample insertion through a front door) and walk away, with no need for follow-up.
  • a clinician would not need to return to transfer samples between preparation and analysis instruments and computers, because the single instrument would be able to perform all of those steps, in precisely the order and timing required by the tests to be performed.
  • the proposed system would allow for a number of types of tests to be performed on each sample, without slowing down or impacting the tests that are performed on adjoining or subsequent samples. For example, hypothetical Sample A could receive tests 4, 5, and 6, that require durations of 5, 7, and 15 minutes respectively, while hypothetical Sample B could receive tests 4, 7, and 8, requiring durations of 5, 10, and 8 minutes respectively.
  • both hypothetical samples A and B (as well as other samples) could be loaded at the same time, and the sample preparation could begin in the order received. Preparation would be followed by sample analysis, such that Sample A might begin analysis as Sample B is finishing its preparation. All actions related to the different sample preparations and analysis could be performed without clinician intervention. Moreover, a clinician could insert additional samples at any time, and such samples could be advanced above any samples waiting in the autoloader should the clinician so desire.
  • such sampling and preparation is possible with a probe washer station that is highly efficient and capable of efficiently washing the sampling probe after each specimen and reagent sampling.
  • a clinician could insert additional samples into the diagnostic instrument at any time, and such samples could be advanced above any samples waiting in the autoloader should the clinician so desire. Regardless of the type of sample tube inserted and where it is inserted, the proposed device is able to process the contents of the tube as prescribed.
  • the proposed device senses whether there is a tube septum, and further determines where the bottom of the tube is located. In this way, nearly any tube, regardless of whether it has a septum and regardless of the size and shape, may be processed by the proposed device.
  • a clinician can insert a variety of tubes, in a variety of configurations, into the proposed device.
  • the device will be able to sense when its probe touches a septum or the bottom of a tube, and will be able to determine whether it should continue in the same direction to pierce the septum, or change directions so as to prevent damage to the tube or probe.
  • Fluid level sensors are known in the art. For example, sight glasses have been used for years as a simple way to see the level inside a container. Coffee makers and coffee dispensers are excellent examples of this type of simple concept, wherein a portion of the fluid is redirected to a small viewing chamber for a visible representation of the fluid level.
  • fluid level sensor uses specific gravity, where an indicator or float rests above one type of material but below another (i.e. a floater on a body of water).
  • indicator or float rests above one type of material but below another (i.e. a floater on a body of water).
  • Various other types of fluid level sensors based on mechanical or physical properties of the surface of the fluid have been explored.
  • Light has also been used to measure the level of fluids. For example, lasers have been pointed at the top of a surface and a timer circuit has been used to measure the time it took a laser pulse to reflect back from the surface. This fluid measurement is based on the reflection of light. Other prior art has focused on the absorption of certain light waves by the fluid to be measured.
  • the present invention contemplates measuring fluid levels based on the refraction and absorption of light.
  • infrared light is directed through a container having a fluid.
  • the container is non-planar, i.e. when the container has at least one surface that is curved, certain light can be expected to refract as it passes through the fluid-filled container.
  • the fluid level drops in the container, such light will not refract in the same way.
  • more of the light will be absorbed when it is directed through a liquid, rather than through an empty container.
  • the level of fluid may be determined.
  • FIG. 1 is a perspective view of one embodiment of the proposed instrument, wherein the instrument is shown coupled with a specimen autoloader;
  • FIG. 2 is an enlarged perspective view of a portion of the diagnostic instrument shown in FIG. 1 ;
  • FIG. 3 is a front perspective view of the diagnostic instrument of FIGS. 1-2 , showing the instrument during operation;
  • FIG. 4 is an enlarged view of the portion of the diagnostic instrument that is capable of sampling a single specimen tube at a time
  • FIG. 5 is a front perspective view of the external housing of the proposed diagnostic instrument shown in FIGS. 1-4 ;
  • FIG. 6 is a front perspective view of the external housing of another embodiment, in which the specimen autoloader is removed and specimen tubes are inserted through the front door;
  • FIG. 7 is a perspective view of one embodiment of a probe washer station used in conjunction with the instrument shown in FIGS. 1-6 ;
  • FIG. 8 is a perspective diagrammatic view of the probe washer station of FIG. 7 ;
  • FIG. 9 is a top diagrammatic view of the probe washer station of FIGS. 7-8 ;
  • FIG. 12 is a front view of one embodiment of the proposed invention, showing a fluid container positioned in a holder;
  • FIG. 13 is a perspective view of the holder of FIG. 12 , showing a plurality of light transmitters and light receptors positioned along the height of the container;
  • FIG. 15 is a perspective view of a coupling embodiment of the present invention.
  • FIG. 16 is an enlarged view of the coupling shown in FIG. 15 ;
  • FIG. 17 shows a filter according to one embodiment of the invention.
  • FIG. 18 is an enlarged view of a probe tip according to yet another embodiment of the invention.
  • diagnostic instrument 10 illustratively performs the following steps once a specimen tube 16 (or specimen tube cassette 14 ) is received. It is contemplated that such steps are performed by instrument 10 without intervention by a clinician, and the steps may be modified, added to, or eliminated depending on the particular test(s) to be performed. It should be understood that while blood tubes are discussed throughout the disclosed embodiment, it is contemplated that other types of body fluids and samples are within the scope of the disclosure, and capable of being analyzed in the proposed instrument 10 . For example, bone marrow, serum, urine, synovial, spinal, peritoneal, plural, and other types of fluids or samples may be tested and analyzed substantially as described below.
  • Instrument 10 is designed to provide automated and integrated specimen sampling, meaning that each of the above steps (if required by the particular tests) can be carried out within and by instrument 10 , without the use of additional diagnostic equipment. Moreover, if desired by the clinician, such steps can be done without any interaction from the clinician.
  • instrument 10 uses a single-axis probe carrier 22 that permits various functions to be performed while probe carrier 22 is moved along single-axis track 24 .
  • probe carrier 22 (and therefore probe 26 ) can be positioned to draw samples from tubes 16 when probe carrier 22 is in position A, can deposit the samples in containment area 20 at position B, and can sample reagents at position C. If a sample is placed in pivotable tray 36 at any point (i.e. for stat processing of a sample), instrument 10 will sense the presence of the sample and insert it ahead of any samples awaiting processing in the autoloader 12 . Probe carrier 22 will then move to position D so that probe 26 can sample from the tubes placed in pivotable tray 36 . Reagents are deposited in containment area 20 either before or after the sample is deposited (or both before and after) for reaction with the sample as required by the particular test(s) to be performed.
  • the steps may be performed in the following order. However, it is contemplated that certain tests may skip one or more steps, or may modify a step in order to achieve the best test results for the desired blood test(s).
  • specimen tubes 16 have a cap 32 (shown in FIG. 1 )
  • the specimen tubes held by cassette 14
  • the specimen tubes may be rocked such that the blood is stirred inside the tube and made more homogenous (for more accurate sampling).
  • Such rocking occurs at station A, and cassette 14 can be seen in its rocked position in FIG. 3 .
  • probe carrier 22 may be directed to move to station C and begin sampling the appropriate portions of reagents 34 for the tests to be performed. However, if the test does not contemplate reagents 34 being placed on the containment area 20 prior to the blood sample, then probe carrier 22 may perform such step after sampling the blood from tube 16 .
  • Reagents 34 may be held in vials, as can be seen at position C. However, reagents may alternatively or additionally be held in reservoirs positioned elsewhere, such as on the plate base 30 (shown in FIGS. 1-2 ), or in other areas (not visible) that can be, for example, plumbed directly to probe 26 .
  • diagnostic instrument 10 also contemplates that a clinician can insert a specimen tube 16 via external door 18 .
  • a tube receiver 38 is provided in illustrated instrument 10 , and such tube receiver may accommodate a variety of types of specimen tubes 16 , including pediatric tubes, as can be seen in FIGS. 2-4 .
  • specimen tubes 16 are held by a pivotable tray 36 that permits easy access and retrieval of specimen tubes 16 .
  • specimen tubes 16 may be held by a rotatable cassette 40 .
  • Probe 26 is washed in probe washer station 28 in substantially the following manner.
  • Probe carrier 22 is moved to position C such that probe 26 can be directed (via motor 42 ) into probe well 44 .
  • Probe well 44 illustratively has an inner diameter that is slightly larger than the outer diameter of probe 26 .
  • a flow of saline and/or air is pumped through nozzle 48 and directed at a downward angle into probe well 44 , as can be seen in FIGS. 7-10 .
  • Nozzle 48 may also be offset slightly so as to create a vortex flow of saline and/or air within probe well 44 , thereby providing additional vortices about probe 26 when it is positioned in probe well 44 . Such vortices assist with removing any fluids or other particles that may be on probe 26 .
  • Upper portion 50 of probe washer station 28 is illustrated to have a rim 52 that assists with containing saline to the probe well 44 and overflow well 46 .
  • Overflow well 46 is provided as an overflow for any saline that may come out of the top of probe well 44 .
  • Both probe well 44 and overflow well 46 are aspirated from the bottom of washer station 28 via exit ports 54 .
  • vacuum pressure assists with the aspiration of exit ports 54 .
  • washer station 28 defines a plurality of mounting apertures 56 , configured to receive a fastener or screw that would secure washer station to device 10 .
  • probe 26 may aspirate a portion of the saline into its internal cavity, and subsequently release the saline back into probe well 44 , thereby rinsing the internal cavity of probe 26 with saline.
  • probe 26 may itself be connected to a saline source, and saline can be directed through the internal cavity of probe 26 while probe 26 sits in probe well 44 . In either case, such a process can be repeated several times as needed to insure the complete washing of specimen and reagent materials from probe 26 .
  • fluids may be plumbed directly into probe 26 .
  • instrument 10 is coupled to a motor 42 that moves probe 26 toward and away from tube 16 .
  • instrument 10 may have information related to the size and shape of the tube 16 , as well as the presence of a septum. For example, if tube 16 were loaded into a cassette 14 , cassette 14 may be bar coded or may otherwise provide an indication of the size and/or shape of tubes 16 found in the cassette 14 . Moreover, in the illustrated embodiments, if tube 16 is in a cassette, it will have a septum (since the illustrated embodiments rock the cassettes 14 after loading).
  • instrument 10 may not be provided with any information as to the size or shape of the tube 16 , as well as the presence of a septum. In such a case, the clinician may provide such information via a user interface. However, in the disclosed embodiment, instrument 10 may also use stall-detecting or touch-sensing features inherent in motor 42 .
  • a clinician may insert a tube 16 into an appropriately sized channel in tube receiver 38 .
  • tube receiver 38 has a plurality of channel sizes so as to accommodate a variety of tube sizes.
  • Instrument 10 will determine where tube 16 is inserted, and move probe carrier 22 to a position above that tube 16 . It is contemplated that tube detection may occur, for example, via a set or array of infrared detectors. The location of the bottom of tube 16 will be known or approximately known because tube receiver 38 will have a structure that holds the tubes 16 in an upright position.
  • probe 26 may encounter a septum, thereby causing resistance to motor 42 .
  • instrument 10 will be able to determine that probe 26 has encountered a septum and not the bottom of tube 16 , since the approximate bottom of tube 16 is known, as described above.
  • the instrument 10 may assume that tubes 16 are bottom-justified when a septum is encountered on the tubes. It may also be possible to detect the size and/or shape of a tube based on the septum's sensed position.
  • motor 42 will be instructed to stop advancing, and retract an adequate distance from which it can aspirate the specimen.
  • the illustrative motor 42 is manufactured by IMS Schneider Electric, and available as model number MCI23A-NPE-03.
  • the present invention provides advantages over the prior art, which incorporated a capacitive sensor to sense the liquid level of specimens found in tubes 16 .
  • Such prior art sensors would sometimes report a false positive when they reached specimen droplets left at the top of the tube (under the septum).
  • the prior art sensors were not able to determine when the bottoms of the tubes 16 were reached.
  • the specimen is sampled by probe 26 and deposited in predetermined wells or tubes in containment area 20 .
  • specimen samples may be placed in more than one well or tube, and the corresponding amount of specimen (such as blood) may be aspirated in advance.
  • Probe 26 is then washed at washer station 28 as described above.
  • the probe carrier 22 may be moved to station C for sampling of the appropriate reagent(s) 34 . Again, if more than one reagent is needed, probe 26 is washed at washer station 28 between each reagent 34 sampling and after the final reagent 34 sampling.
  • plate base 30 may be positioned on a rotating axis so that each well or tube could be presented to probe 26 , depending on the point of rotation of the plate base 30 .
  • Such a configuration and rotational movement of plate base 30 is disclosed in U.S. patent application Ser. No. 11/804,721, incorporated herein by reference.
  • a multi-axis probe carrier may also accomplish these goals, certain advantages exist for a single-axis device. For example, a single axis device requires fewer parts and less programming, yields a smaller instrument 10 footprint, is easier to align, is more reliable and more stable, and ultimately faster in its movement between stations.
  • test equipment After placement in wells or tubes, the specimen samples are left to react with reagents for a specific amount of time (depending on the reagents and the tests to be performed) and then processed through the flow cytometer for analysis. It is contemplated that other test equipment may also be incorporated, such as equipment that uses electronic volume for cell sizing and differentiation, or hemoglobin measurement using absorbance.
  • containment area 20 serves as a common interface between sample preparation and analysis.
  • containment area 20 can include fixed or detachable and/or disposable or reusable components, allowing a clinician to opt to throw away the entire interface (as in the example of a microtiter plate) after use.
  • containment area 20 provides a system with less exposure to mistakes and external or environmental influences.
  • a software scheduler (not shown) is also incorporated in the disclosed system.
  • the software scheduler is illustratively programmed to recalculate available windows for fixed reaction kinetics (optimizing throughput while maintaining reproducible reaction kinetics) (i.e. antibody incubations, RBC lysing time, reaction quench time, etc.).
  • barcodes may be assigned to the reagent vials 34 , specimen tubes 16 (with different bar codes for different patients and/or sizes), sheath fluids, common interfaces (i.e. containment areas 20 ), preparation reagents, bead reagents, cassettes 14 , etc.
  • barcodes may be assigned to the reagent vials 34 , specimen tubes 16 (with different bar codes for different patients and/or sizes), sheath fluids, common interfaces (i.e. containment areas 20 ), preparation reagents, bead reagents, cassettes 14 , etc.
  • the software scheduler may be configured to perform the following steps.
  • instrument 10 With all sample preparation and analysis fully integrated in one instrument 10 , a clinic need not perform slow and tedious “batch processing,” where the samples are collected and processing started once a sufficient number are collected—progressing through each step of the blood processing with the entire group of samples.
  • instrument 10 is configured to automatically prepare patient samples in containment area 20 , so there are no daughter tubes to label and keep track of, and significantly less blood and reagents are needed. Samples can be loaded onto the system at any time, and in the illustrative embodiment, each will be automatically processed and exit the system pipeline in approximately 15 minutes. Subsequent samples could exit the system pipeline in approximately 90 second intervals, although exact times will vary depending on the tests to be performed and required sample preparation times.
  • a significant advantage is the cost savings for a lab. Not only can more samples be processed in a single day, by using one system, there are lower system costs, lower reagent costs and reduced hands-on labor. Accordingly, the overall cost to own and operate the instrument 10 is significantly lower.
  • diagnostic instrument 10 is compact, measuring only 31 inches wide, inclusive of the autoloader portion 12 .
  • the embodiment shown in FIG. 6 without an autoloader portion, requires an even smaller footprint.
  • a touch-screen computer/screen (not shown) can also be conveniently placed on top of the system, keeping the footprint small and freeing up valuable space for the lab.
  • the proposed system may be ideal for clinical researchers running one or more fixed immune surveillance panels for contract research, pharmaceutical drug development, and research in university medical centers and reference labs. It is further contemplated that the standardized immune monitoring panels may be monitoring for immunodeficiency (HIV-AIDS), autoimmune diseases, organ transplant response, infectious diseases, oncology and others.
  • HIV-AIDS immunodeficiency
  • autoimmune diseases autoimmune diseases
  • organ transplant response infectious diseases
  • infectious diseases infectious diseases
  • a translucent or transparent container is contemplated, such that infrared light may pass through the container.
  • Container 110 may also have at least one non-planar side 112 so that light passing through it refracts.
  • transmitter 114 and receptor 116 are coupled to a frame 118 that can be positioned around at least a portion of container 110 .
  • light receptor 116 can detect a difference in the strength of light received from light transmitter 114 . For example, based on the strength of the light received from transmitter 114 , light receptor 116 will be able to sense whether the light passed through a liquid on its way to receptor 116 . This information will be used to determine the level of the fluid.
  • a fluid such as water or saline
  • the present disclosure uses the absorbance spectra of water, which has a broad peak starting around 890 nm.
  • Container 110 may be constructed of polypropylene, which also has a known absorbance spectra.
  • transmitter 114 and receptor 116 may be positioned at a single point on the container 110 , such that it can indicate when the fluid has been depleted beyond a pre-selected level—similar to a low fuel warning light in a vehicle.
  • transmitters 114 and receptors 116 may be positioned at various locations along the height of container 110 , as can be seen in FIG. 13 , such that a user can determine with better accuracy the fluid level at numerous points on the container.
  • Transmitters 114 and receptors 116 may be user configurable (i.e. the positions may be changed by a user) or may be set by the manufacturer.
  • Transmitter 114 is illustratively an LED from Panasonic, part number: LNA 2904L.
  • Receptor 116 illustratively uses a transistor from Fairchild Optical Electrical: part number QSD123.
  • FIGS. 15-16 Still another embodiment of the present disclosure is shown in FIGS. 15-16 in the form of a device coupling 210 .
  • a coupling may be contrasted, for example, with the prior art coupling shown in FIG. 14 .
  • device coupling 210 includes a lead screw 212 having a tapered surface 214 formed on one end 216 of the shaft 218 .
  • tapered surface 214 may be fashioned similar to a Brown and Sharpe tapered surface, and may be ground to its shape.
  • a complementary and mating taper 219 is formed in female portion 220 , creating a recess 228 .
  • Female portion 220 may be attached to a motor 222 , or may be an integral part of motor 222 .
  • Shaft 218 has a threaded hole 224 at end 216 of the shaft 218 .
  • tapered surface 214 is inserted into recess 228 of female portion 220 .
  • a screw (not shown) is used to pull shaft 218 into female portion 220 .
  • the surface area between tapered surface 214 and mating taper 219 are sufficient to provide enough friction to prevent rotation of the parts relative to each other at the typical operating speeds of the motor.
  • the screw functions merely to keep the two surfaces 214 , 219 joined.
  • Disassembly of device 210 is accomplished by loosening the screw and lightly tapping the first end 216 of shaft 218 out of its mated position. Another advantage of the present invention is ease of separation of two expensive components.
  • flow cytometers generally comprise a small hole (typically square or rectangular in cross section) on the order of magnitude of 100-300 microns per side and usually greater than 1000 microns long.
  • the diagnostic measurements that flow cytometers make are on particles that are usually less than 50% of the cross sectional area of the measuring hole or aperture.
  • the small size is necessary to hydro-dynamically focus the particles to the center of the aperture where the particles are interrogated with a laser beam. This can have the negative consequence of being very susceptible to clogs.
  • One method is to have automated back-flushing routines that are activated by some method of automatically detecting clogs.
  • this produces significant slow-down in the operation of the instruments, and is not always 100% effective. Failure to remove the clog by the automated routines requires operator or service intervention.
  • the filter has the following properties:
  • Such a system may be used, for example, with a flow cytometer aperture that forms an equilateral triangle.
  • FIG. 18 One embodiment of a probe tip associated with the present invention is shown in FIG. 18 .
  • One of the elements of the disclosed system that assists with producing reliable counting, mixing and minimal debris is the probe 26 geometry.
  • an illustrative probe 26 has a solid blunt end 310 that can eliminate coring of the septum material.
  • Probe 26 may also have two holes 312 (one of which is visible in FIG. 18 ), such holes being substantially the same size as the internal bore (not shown) of probe 26 . This construction has been shown to improve mixing and reduce the break up of cells caused by high-velocity shear forces.
  • Holes 312 are located near end 310 of probe 26 so as to reduce the amount of blood sticking to the probe. This improves the reproducibility of the counting. The amount of blood (or any other fluid) sticking to the outside of probe 26 due to surface tension can dramatically affect the counting.

Landscapes

  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • General Engineering & Computer Science (AREA)
  • Power Engineering (AREA)
  • Mechanical Engineering (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Investigating Or Analyzing Materials By The Use Of Ultrasonic Waves (AREA)
  • Optical Measuring Cells (AREA)
  • Measurement Of Levels Of Liquids Or Fluent Solid Materials (AREA)
US13/696,277 2010-05-05 2011-05-05 Diagnostic instrument and flow process Abandoned US20130234053A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US13/696,277 US20130234053A1 (en) 2010-05-05 2011-05-05 Diagnostic instrument and flow process

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US33178910P 2010-05-05 2010-05-05
US33178510P 2010-05-05 2010-05-05
US33179510P 2010-05-05 2010-05-05
US33179310P 2010-05-05 2010-05-05
PCT/US2011/035420 WO2011140390A2 (en) 2010-05-05 2011-05-05 Diagnostic system and components
US13/696,277 US20130234053A1 (en) 2010-05-05 2011-05-05 Diagnostic instrument and flow process

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2011/035420 A-371-Of-International WO2011140390A2 (en) 2010-05-05 2011-05-05 Diagnostic system and components

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US13/961,275 Continuation-In-Part US20140170739A1 (en) 2010-05-05 2013-08-07 Inline sample filter for a flow cytometer
US14/836,087 Continuation US11067110B2 (en) 2010-05-05 2015-08-26 Device coupling for a motor

Publications (1)

Publication Number Publication Date
US20130234053A1 true US20130234053A1 (en) 2013-09-12

Family

ID=44904488

Family Applications (2)

Application Number Title Priority Date Filing Date
US13/696,277 Abandoned US20130234053A1 (en) 2010-05-05 2011-05-05 Diagnostic instrument and flow process
US14/836,087 Active 2033-04-15 US11067110B2 (en) 2010-05-05 2015-08-26 Device coupling for a motor

Family Applications After (1)

Application Number Title Priority Date Filing Date
US14/836,087 Active 2033-04-15 US11067110B2 (en) 2010-05-05 2015-08-26 Device coupling for a motor

Country Status (8)

Country Link
US (2) US20130234053A1 (ko)
EP (2) EP2998745A1 (ko)
JP (2) JP2013525817A (ko)
KR (1) KR20130098169A (ko)
CN (2) CN102933948B (ko)
BR (1) BR112012028318A2 (ko)
RU (1) RU2587328C2 (ko)
WO (1) WO2011140390A2 (ko)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20170185815A1 (en) * 2015-12-28 2017-06-29 Aoi Seiki Co., Ltd. Sample processing apparatus and sample processing method
US11099178B2 (en) * 2011-10-28 2021-08-24 Torsten Matthias Device and method for detecting substances present in biological or chemical samples
US20220341850A1 (en) * 2021-04-23 2022-10-27 Poppy Health, Inc. System and method for characterizing, monitoring, & detecting bioaerosol presence & movement in an indoor environment
US20230266353A1 (en) * 2015-03-03 2023-08-24 HighRes Biosolutions, Inc. Pipettor system

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BR112012029520B1 (pt) * 2010-05-05 2021-07-06 Beckman Coulter Biomedical, Llc sistema para analisar uma amostra celular em um tubo de amostra, e método de preparação e análise de uma amostra em um tubo
JP6649088B2 (ja) 2014-01-07 2020-02-19 株式会社日立ハイテクノロジーズ 自動分析装置
CN109171021B (zh) * 2018-08-22 2021-08-27 青岛颐中科技有限公司 电子烟吸烟机的供料系统
CN113125778A (zh) * 2019-12-31 2021-07-16 科美诊断技术股份有限公司 试剂管理方法和装置
CN112170361B (zh) * 2020-10-09 2023-09-22 嘉兴晶铸生物科技有限公司 一种集成式清洗装置及其集成式清洗结构组件
CN112303136B (zh) * 2020-10-29 2021-07-13 瑞安市龙派机械制造有限公司 一种用于自动脱皮机的转盘连接件及其使用方法
CN114152477A (zh) * 2021-11-26 2022-03-08 上海品峰医疗科技有限公司 一种用于真空采血管穿刺取样针的防撞保护方法

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6592822B1 (en) * 1998-05-14 2003-07-15 Luminex Corporation Multi-analyte diagnostic system and computer implemented process for same
US20060229367A1 (en) * 2005-04-07 2006-10-12 Xy, Inc. Flow path conditioner system
US20070003434A1 (en) * 2005-07-01 2007-01-04 Honeywell International Inc. Flow metered analyzer
US20070278154A1 (en) * 2006-05-30 2007-12-06 Sysmex Corporation Cell processing method and cell processing apparatus
WO2008019448A1 (en) * 2006-08-18 2008-02-21 Macquarie University Time gated fluorescent flow cytometer
US20080092961A1 (en) * 2006-03-08 2008-04-24 Bair Nathaniel C Flow cytometer system with unclogging feature
JP2010230629A (ja) * 2009-03-30 2010-10-14 Mitsui Eng & Shipbuild Co Ltd フローサイトメータおよびサンプル液供給装置
US20110134426A1 (en) * 2009-12-04 2011-06-09 Life Technologies Corporation Apparatuses, systems, methods, and computer readable media for acoustic flow cytometry.

Family Cites Families (54)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US964579A (en) * 1909-12-14 1910-07-19 John Hall Stephens Hose-coupling.
US1708981A (en) 1927-08-24 1929-04-16 Richard N Vickers Wrist pin
US2835518A (en) * 1954-03-19 1958-05-20 Ingersoll Rand Co Rotary shaft driving connection
US3259891A (en) * 1964-05-01 1966-07-05 Coulter Electronics Debris alarm
DE1938448C3 (de) * 1969-07-29 1982-02-25 Spieth, Rudolf, 7300 Esslingen Gewindering
GB1527956A (en) 1976-03-05 1978-10-11 Ringfeeder Gmbh Demountable clamping set for connecting a shaft to a hub
JPS5742562Y2 (ko) * 1978-02-28 1982-09-20
JPS58163822A (ja) 1982-03-20 1983-09-28 Okuma Mach Works Ltd 差動ねじの軸継手
EP0171156B1 (en) * 1984-07-12 1988-03-30 Masanori Mochizuki Shaft coupling
US4791699A (en) * 1984-11-09 1988-12-20 Royal Appliance Manufacturing Co. Hand vacuum cleaner
JPS61149615A (ja) * 1984-12-24 1986-07-08 Masanori Mochizuki 回転体固定方法
JPS6246021A (ja) 1985-08-22 1987-02-27 Toyoda Mach Works Ltd 締結装置
JPS63160436A (ja) 1986-12-24 1988-07-04 Sumitomo Electric Ind Ltd 光信号線路の保守方法
JPS63188331A (ja) 1987-01-30 1988-08-03 岩崎電気株式会社 水耕栽培装置
DE3786657D1 (de) * 1987-02-17 1993-08-26 Ratcom Inc Durchflusszytometrie.
US5245318A (en) 1987-07-24 1993-09-14 Canon Kabushiki Kaisha Particle analyzing apparatus having pressure control system
JP2575149B2 (ja) * 1987-09-30 1997-01-22 キヤノン株式会社 粒子解析装置
US5197769A (en) * 1988-01-27 1993-03-30 Nwd International, Inc. Adjustable O-ring port fitting for a hydraulic coupling
JPH01222886A (ja) 1988-02-29 1989-09-06 Pentel Kk ロボットの上下軸負荷に対するバランス力調整装置
JPH01269723A (ja) 1988-04-22 1989-10-27 Tsubakimoto Chain Co 軸と回転体の締結装置
US5010970A (en) * 1988-05-27 1991-04-30 Mazda Motor Corporation Power-assisted steering system
CA1322773C (en) * 1989-07-28 1993-10-05 Erich F. Klementich Threaded tubular connection
JPH0587151A (ja) 1991-09-26 1993-04-06 Yokogawa Electric Corp テーパシヤフト結合装置
JPH05301150A (ja) * 1992-04-24 1993-11-16 Mori Seiki Co Ltd 工作機械の工具アタッチメント
JP3348106B2 (ja) * 1992-05-06 2002-11-20 株式会社森精機製作所 門型複合加工機
RU2117514C1 (ru) * 1992-08-31 1998-08-20 Порэс Медиа Корпорейшн Пористый фильтрующий элемент конической формы и узлы фильтра
CN1036022C (zh) * 1992-09-05 1997-10-01 德莱塞·兰特公司 杆与构件连接时杆轴向可调的连接附加件
US5475487A (en) * 1994-04-20 1995-12-12 The Regents Of The University Of California Aqueous carrier waveguide in a flow cytometer
JPH08297121A (ja) * 1995-04-26 1996-11-12 Hitachi Ltd 粒子分析装置
IT1278065B1 (it) 1995-05-12 1997-11-17 Cml Costr Mecc Liri Srl Centinatrice universale.
US5641456A (en) * 1995-09-13 1997-06-24 Marco Equipment Distributors, Inc. Apparatus and method for cleaning
JPH10185025A (ja) * 1996-12-26 1998-07-14 Sanko Kogyo Kk 容器弁接続継手
US6183697B1 (en) * 1997-05-27 2001-02-06 Sysmex Corporation Particle measuring apparatus
JPH11270520A (ja) * 1998-03-24 1999-10-05 Matsushita Giken Kk マイクロ部品の結合部構造
JP2001090544A (ja) 1999-09-20 2001-04-03 Suzuki Motor Corp エンジン発電装置の連結構造
US6784981B1 (en) * 2000-06-02 2004-08-31 Idexx Laboratories, Inc. Flow cytometry-based hematology system
US6751293B1 (en) * 2001-10-05 2004-06-15 Varian Medical Systems, Inc. Rotary component support system
US7201875B2 (en) * 2002-09-27 2007-04-10 Becton Dickinson And Company Fixed mounted sorting cuvette with user replaceable nozzle
US6797185B2 (en) * 2002-10-25 2004-09-28 Basf Corporation Filtration method for graft polymer polyols
US8012768B2 (en) * 2003-07-18 2011-09-06 Bio-Rad Laboratories, Inc. System and method for multi-analyte detection
JP4106000B2 (ja) * 2003-08-25 2008-06-25 アイダエンジニアリング株式会社 マイクロチップ
US20070248958A1 (en) * 2004-09-15 2007-10-25 Microchip Biotechnologies, Inc. Microfluidic devices
FR2876755B1 (fr) * 2004-10-20 2007-01-26 Pcm Pompes Sa Dispositif de pompage a pompe a cavites progressives
US7675210B2 (en) * 2005-03-11 2010-03-09 Panasonic Corporation Hydrodynamic bearing and method for manufacturing the same, and spindle motor and method for manufacturing the same
US20070025879A1 (en) * 2005-07-27 2007-02-01 Dakocytomation Denmark A/S Method and apparatus for syringe-based sample introduction within a flow cytometer
EP1757826B1 (en) * 2005-08-24 2009-01-21 Mecos Traxler AG Rotor shaft for a magnetic bearing device
US8070375B2 (en) * 2005-09-21 2011-12-06 Xerox Corporation Coupling and shaft assembly
KR100766885B1 (ko) * 2006-04-14 2007-10-18 신윤호 온라인 분석기용 울트라 필터레이션 시스템
EP2055329B1 (en) * 2006-06-16 2016-03-09 Terumo Kabushiki Kaisha Blood treatment filter and blood treatment circuit
US20080076587A1 (en) * 2006-09-25 2008-03-27 Reliance Electric Technologies, Llc Flange shouldered screw-in stub shaft
US8445286B2 (en) * 2006-11-07 2013-05-21 Accuri Cytometers, Inc. Flow cell for a flow cytometer system
JP2009156354A (ja) * 2007-12-27 2009-07-16 Jtekt Corp ボールねじ装置
US8170271B2 (en) * 2008-06-25 2012-05-01 Jadak Llc System and method for test tube and cap identification
AU2009299098B2 (en) * 2008-10-02 2014-07-10 Victa Lawncare Pty Ltd. Drive shaft joiner system

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6592822B1 (en) * 1998-05-14 2003-07-15 Luminex Corporation Multi-analyte diagnostic system and computer implemented process for same
US20060229367A1 (en) * 2005-04-07 2006-10-12 Xy, Inc. Flow path conditioner system
US20070003434A1 (en) * 2005-07-01 2007-01-04 Honeywell International Inc. Flow metered analyzer
US20080092961A1 (en) * 2006-03-08 2008-04-24 Bair Nathaniel C Flow cytometer system with unclogging feature
US20070278154A1 (en) * 2006-05-30 2007-12-06 Sysmex Corporation Cell processing method and cell processing apparatus
WO2008019448A1 (en) * 2006-08-18 2008-02-21 Macquarie University Time gated fluorescent flow cytometer
JP2010230629A (ja) * 2009-03-30 2010-10-14 Mitsui Eng & Shipbuild Co Ltd フローサイトメータおよびサンプル液供給装置
US20110134426A1 (en) * 2009-12-04 2011-06-09 Life Technologies Corporation Apparatuses, systems, methods, and computer readable media for acoustic flow cytometry.

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11099178B2 (en) * 2011-10-28 2021-08-24 Torsten Matthias Device and method for detecting substances present in biological or chemical samples
US11099179B2 (en) * 2011-10-28 2021-08-24 Torsten Matthias Device and method for detecting substances present in biological or chemical samples
US20230266353A1 (en) * 2015-03-03 2023-08-24 HighRes Biosolutions, Inc. Pipettor system
US11933805B2 (en) * 2015-03-03 2024-03-19 HighRes Biosolutions, Inc. Pipettor system
US20170185815A1 (en) * 2015-12-28 2017-06-29 Aoi Seiki Co., Ltd. Sample processing apparatus and sample processing method
US10402614B2 (en) * 2015-12-28 2019-09-03 Aoi Seiki Co., Ltd. Sample processing apparatus and sample processing method
US20220341850A1 (en) * 2021-04-23 2022-10-27 Poppy Health, Inc. System and method for characterizing, monitoring, & detecting bioaerosol presence & movement in an indoor environment

Also Published As

Publication number Publication date
RU2012152091A (ru) 2014-06-10
EP2998745A1 (en) 2016-03-23
US11067110B2 (en) 2021-07-20
EP2567211A2 (en) 2013-03-13
KR20130098169A (ko) 2013-09-04
RU2587328C2 (ru) 2016-06-20
CN102933948A (zh) 2013-02-13
BR112012028318A2 (pt) 2016-11-01
WO2011140390A3 (en) 2012-01-26
CN102933948B (zh) 2015-06-24
US20160053790A1 (en) 2016-02-25
JP2013525817A (ja) 2013-06-20
WO2011140390A2 (en) 2011-11-10
EP2567211A4 (en) 2015-04-01
JP2016014478A (ja) 2016-01-28
CN105044376A (zh) 2015-11-11

Similar Documents

Publication Publication Date Title
US11067110B2 (en) Device coupling for a motor
US11169061B2 (en) Automated system for processing particles
EP2466291B1 (en) Cuvette for photometric measurement of small liquid volumes
EP3570041B1 (en) Sample preparation apparatus and sample preparation method, cell analyzer and cell analysis method
US9329111B2 (en) Sample preparation apparatus
CA2663864C (en) Device for automatically adjusting the bacterial inoculum level of a sample
EP1526370B1 (en) Patient sample classification based upon low angle light scattering
US20110176976A1 (en) Sample preparation apparatus
EP3508858A1 (en) Sample measurement method and sample measurement device
KR20050121731A (ko) 분주용 실린더, 대용량 분주장치 및 대용량 분주장치의사용방법
RU2753649C1 (ru) Устройство и способ определения скорости оседания эритроцитов и других связанных параметров
CN104662406A (zh) 确定血液沉降速率和与其有关的其它参数的仪器及方法
JPH08114600A (ja) 生体試料分析システム
JP6180585B2 (ja) 診断機器及びフロープロセス
CN220340035U (zh) 反应杯、抓手装置和样本分析仪

Legal Events

Date Code Title Description
AS Assignment

Owner name: BECKMAN COULTER BIOMEDICAL, LLC, DISTRICT OF COLUM

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:BLUE OCEAN BIOMEDICAL, LLC;REEL/FRAME:028014/0075

Effective date: 20120328

AS Assignment

Owner name: BECKMAN COULTER, INC., CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:BLUE OCEAN BIOMEDICAL, LLC;REEL/FRAME:029543/0601

Effective date: 20120328

AS Assignment

Owner name: BECKMAN COULTER BIOMEDICAL, LLC., DISTRICT OF COLU

Free format text: CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNEE (RECEIVING PARTY) PREVIOUSLY RECORDED ON REEL 029543 FRAME 0601. ASSIGNOR(S) HEREBY CONFIRMS THE CORRECTION OF THE ASSIGNEE FROM BECKMAN COULTER, INC. TO BECKMAN COULTER BIOMEDICAL, LLC.;ASSIGNOR:BLUE OCEAN BIOMEDICAL, LLC;REEL/FRAME:029564/0962

Effective date: 20120328

AS Assignment

Owner name: BLUE OCEAN BIOMEDICAL, LLC, FLORIDA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:THOMAS, RICHARD A.;THOMAS, MICHAEL A.;REEL/FRAME:030465/0298

Effective date: 20130516

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION

AS Assignment

Owner name: BECKMAN COULTER, INC., CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:BECKMAN COULTER BIOMEDICAL, LLC;REEL/FRAME:052992/0078

Effective date: 20200512