US20130234053A1 - Diagnostic instrument and flow process - Google Patents
Diagnostic instrument and flow process Download PDFInfo
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- 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
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- flow cytometer
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Images
Classifications
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- 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
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- 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
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- G—PHYSICS
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- 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
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- 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
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- G—PHYSICS
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- 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
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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- 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
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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- 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
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- H—ELECTRICITY
- H02—GENERATION; CONVERSION OR DISTRIBUTION OF ELECTRIC POWER
- H02K—DYNAMO-ELECTRIC MACHINES
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- 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.
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Abstract
Description
- The present invention relates generally to a diagnostic system, and more specifically to a diagnostic system and instrument that uses a probe. In the illustrated embodiments, 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.
- Cellular analysis instruments using flow cytometers are known in the field. See, for example, U.S. patent application Ser. No. 11/825,523, incorporated herein by reference. 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. By studying the filtered EM spectrum, analyses of the cellular content can be performed and certain characteristics and values can be reported.
- In one illustrated embodiment, 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. Advantageously, such a plurality of samples may be processed and analyzed continuously.
- A specimen autoloader can be provided for moderate-to-high volume laboratories. According to the embodiments disclosed herein, 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. For example, 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. Additionally, 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 receivetests 4, 7, and 8, requiring durations of 5, 10, and 8 minutes respectively. - Using the proposed device, 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.
- According to the present invention, 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.
- In another aspect of the invention, 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.
- Hospitals around the world use a wide variety of tubes for drawing specimens (e.g. blood) from patients. Some tubes are covered with a cap or septum, while others are open tubes. It would be time consuming for the clinician to identify every type of tube that is to be analyzed.
- 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.
- In summary, 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.
- Another example of a 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). 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.
- In contrast to the above-disclosed systems, the present invention contemplates measuring fluid levels based on the refraction and absorption of light. In the disclosed method, infrared light is directed through a container having a fluid. When 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. However, as the fluid level drops in the container, such light will not refract in the same way. Moreover, more of the light will be absorbed when it is directed through a liquid, rather than through an empty container. Thus, by monitoring the refraction of light at points along the height of the container, the level of fluid may be determined.
- Additional features of the disclosure will become apparent to those skilled in the art upon consideration of the following detailed description of preferred embodiments exemplifying the best mode of carrying out the invention as presently perceived.
- The detailed description particularly refers to the accompanying figures in which:
-
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 inFIG. 1 ; -
FIG. 3 is a front perspective view of the diagnostic instrument ofFIGS. 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 inFIGS. 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 inFIGS. 1-6 ; -
FIG. 8 is a perspective diagrammatic view of the probe washer station ofFIG. 7 ; -
FIG. 9 is a top diagrammatic view of the probe washer station ofFIGS. 7-8 ; -
FIG. 10 is a front elevation view of the probe washer station ofFIGS. 7-9 ; -
FIG. 11 is a side elevation view of the probe washer station ofFIGS. 7-10 ; -
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 ofFIG. 12 , showing a plurality of light transmitters and light receptors positioned along the height of the container; -
FIG. 14 is a front elevation view of a prior art lead screw coupling; -
FIG. 15 is a perspective view of a coupling embodiment of the present invention; -
FIG. 16 is an enlarged view of the coupling shown inFIG. 15 ; -
FIG. 17 shows a filter according to one embodiment of the invention; and -
FIG. 18 is an enlarged view of a probe tip according to yet another embodiment of the invention. - One embodiment of the present disclosure is shown in
FIGS. 1-6 in the form of adiagnostic instrument 10. In the illustrated embodiment, anautoloader portion 12 can be seen having a number ofspecimen cassettes 14 loaded thereon. In such an embodiment,cassettes 14 can be loaded with a plurality of identical specimen tubes or vials (hereinafter referred to as “tubes”) 16, a variety ofspecimen tubes 16, or merely asingle specimen tube 16. The cassettes are then top-loaded intoautoloader portion 12 and processed in the order received. In the alternative, i.e. when faster, single-sample processing is desired, a specimen tube can be inserted directly into an alternative specimen entry point, i.e. door 18 (visible inFIG. 5 ) and processed ahead of any awaitingcassettes 14, as shown inFIG. 4 . This provides for stat access to the testing by a clinician, with a capability to run tests immediately, thereby interrupting (but not negatively affecting) testing of other specimen tubes when desired by the clinician. Additionally, a specimen tube that has compromised or no bar coding (discussed infra) may be inserted manually. - As described in detail below,
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 byinstrument 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 proposedinstrument 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. -
- Mixing (e.g. rocking) samples while still in specimen tubes 16 (in the autoloader embodiment)
- Piercing the cap of
specimen tubes 16 and sampling the requisite amount of the specimen - Reading barcodes to confirm sample/patient ID and/or to confirm type/size of tube
- Matching ID, test(s) to be performed, & reagents required, and assigning a serial number for tracking by the computer
- Placing the specimen/sample in selected empty tubes or wells in a containment area 20 (shown, for example, as a microtiter plate in
FIGS. 1-3 ), for further processing - Adding appropriate reagents in the appropriate sequence and timing so as to properly prepare the samples for the tests to be performed
- Allowing the samples to react with reagents for prescribed incubation times (variable based on the reagent)
- Splitting the sample into a plurality of tubes/wells in the containment area 20 (if desired or required by testing)
- Tracking all samples, cassettes, reagents & relevant positions via barcodes or other type of tracking device (e.g. RFID)
- Timely aspirating the prepared sample/reagent combination from the containment area and analyzing it via flow cytometer (while preparing subsequent samples)
- Auto-verifying results or holding results for review, depending on clinician-initiated decision rules.
-
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 byinstrument 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. - In the illustrated embodiment,
instrument 10 uses a single-axis probe carrier 22 that permits various functions to be performed whileprobe carrier 22 is moved along single-axis track 24. For example, probe carrier 22 (and therefore probe 26) can be positioned to draw samples fromtubes 16 whenprobe carrier 22 is in position A, can deposit the samples incontainment area 20 at position B, and can sample reagents at position C. If a sample is placed inpivotable 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 theautoloader 12.Probe carrier 22 will then move to position D so thatprobe 26 can sample from the tubes placed inpivotable tray 36. Reagents are deposited incontainment 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).
- First,
specimen tubes 16 may be loaded into apre-configured cassette 14 that is appropriate for theparticular specimen tubes 16 to be used. For example,specimen tubes 16 may be a commonly found size of 13 mm×75 mm specimen tube, in which case the five-tube cassette 14 shown inFIGS. 1 and 3 may be used. However, it should be understood that a variety of sizes and types ofspecimen tubes 16 may be used with the present invention, andcassettes 14 may be designed accordingly. Acassette 14 may even be configured to hold a variety ofspecimen tubes 16. As stated above, various sizes ofspecimen tubes 16 may also be inserted individually throughdoor 18, shown inFIG. 5 . - If
specimen tubes 16 have a cap 32 (shown inFIG. 1 ), the specimen tubes (held by cassette 14) 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, andcassette 14 can be seen in its rocked position inFIG. 3 . - During rocking of
cassette 14,probe carrier 22 may be directed to move to station C and begin sampling the appropriate portions ofreagents 34 for the tests to be performed. However, if the test does not contemplatereagents 34 being placed on thecontainment area 20 prior to the blood sample, then probecarrier 22 may perform such step after sampling the blood fromtube 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 inFIGS. 1-2 ), or in other areas (not visible) that can be, for example, plumbed directly to probe 26. - As set forth above,
diagnostic instrument 10 also contemplates that a clinician can insert aspecimen tube 16 viaexternal door 18. To accommodate this, atube receiver 38 is provided in illustratedinstrument 10, and such tube receiver may accommodate a variety of types ofspecimen tubes 16, including pediatric tubes, as can be seen inFIGS. 2-4 . In the illustrated example,specimen tubes 16 are held by apivotable tray 36 that permits easy access and retrieval ofspecimen tubes 16. In an alternative embodiment, shown inFIG. 3 ,specimen tubes 16 may be held by arotatable cassette 40. - In between and after sampling of specimens and/or
reagents 34,probe carrier 22 may move to aprobe washer station 28, so thatprobe 26 can be washed. Washing theprobe 26 prevents cross-contamination and therefore prevents inaccurate test results. - Probe
washer station 28 is shown in detail inFIGS. 7-11 . According to the illustrated embodiment,probe washer station 28 includes a probe well 44 and anoverflow well 46. -
Probe 26 is washed inprobe washer station 28 in substantially the following manner.Probe carrier 22 is moved to position C such thatprobe 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 ofprobe 26. Asprobe 26 is directed into probe well 44, a flow of saline and/or air is pumped throughnozzle 48 and directed at a downward angle into probe well 44, as can be seen inFIGS. 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 aboutprobe 26 when it is positioned in probe well 44. Such vortices assist with removing any fluids or other particles that may be onprobe 26. - While the present disclosure contemplates the use of saline (which could be combined with air) as a washing solution, it should be understood that other types of fluids, or even the flow of air, may be desirable in certain applications.
-
Upper portion 50 ofprobe washer station 28 is illustrated to have arim 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 ofwasher station 28 viaexit ports 54. In the illustrative embodiment, vacuum pressure assists with the aspiration ofexit ports 54. - In the illustrated embodiment,
washer station 28 defines a plurality of mountingapertures 56, configured to receive a fastener or screw that would secure washer station todevice 10. - It is contemplated that
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 ofprobe 26 with saline. In the alternative,probe 26 may itself be connected to a saline source, and saline can be directed through the internal cavity ofprobe 26 whileprobe 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 fromprobe 26. In yet another embodiment, fluids may be plumbed directly intoprobe 26. - The
probe carrier 22 is coupled to a motor 42 that movesprobe 26 toward and away fromtube 16. In some cases,instrument 10 may have information related to the size and shape of thetube 16, as well as the presence of a septum. For example, iftube 16 were loaded into acassette 14,cassette 14 may be bar coded or may otherwise provide an indication of the size and/or shape oftubes 16 found in thecassette 14. Moreover, in the illustrated embodiments, iftube 16 is in a cassette, it will have a septum (since the illustrated embodiments rock thecassettes 14 after loading). - In the event a clinician inserts a
specimen tube 16 throughdoor 18, such thattube 16 is placed inpivotable tray 36,instrument 10 may not be provided with any information as to the size or shape of thetube 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. - For example, a clinician may insert a
tube 16 into an appropriately sized channel intube receiver 38. (Illustratively,tube receiver 38 has a plurality of channel sizes so as to accommodate a variety of tube sizes.)Instrument 10 will determine wheretube 16 is inserted, and moveprobe carrier 22 to a position above thattube 16. It is contemplated that tube detection may occur, for example, via a set or array of infrared detectors. The location of the bottom oftube 16 will be known or approximately known becausetube receiver 38 will have a structure that holds thetubes 16 in an upright position. - As motor 42 begins to move
probe 26 towardtube 16,probe 26 may encounter a septum, thereby causing resistance to motor 42. The present invention contemplates thatinstrument 10 will be able to determine thatprobe 26 has encountered a septum and not the bottom oftube 16, since the approximate bottom oftube 16 is known, as described above. - If a septum is encountered, motor 42 will be instructed to proceed through the septum and on toward the bottom of
tube 16. If no septum is encountered,probe 26 will continue toward the bottom oftube 16 without interruption. In one embodiment, theinstrument 10 may assume thattubes 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. - In both cases, once probe 26 encounters resistance at a position that approximates the bottom of
tube 16, 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). Moreover, the prior art sensors were not able to determine when the bottoms of thetubes 16 were reached. - After sufficient mixing is done of the specimen within the tubes (i.e. at station A), the specimen is sampled by
probe 26 and deposited in predetermined wells or tubes incontainment area 20. Depending on the test(s) to be performed, 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 atwasher station 28 as described above. - Depending on whether or not reagents are added to the specimen samples after depositing them in
containment area 20, theprobe 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 atwasher station 28 between each reagent 34 sampling and after thefinal reagent 34 sampling. - In order to deposit specimen samples and reagents in each well or tube of
containment area 20,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 theplate base 30. Such a configuration and rotational movement ofplate base 30 is disclosed in U.S. patent application Ser. No. 11/804,721, incorporated herein by reference. - While it is contemplated that 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. - 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.
- Conveniently,
containment area 20 serves as a common interface between sample preparation and analysis. Moreover,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. By serving as the common interface between the preparation arm and analysis arm,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.).
- It is also contemplated that numerous items can be barcoded and tracked during operation. Such barcoding and tracking can be registered by the software scheduler. For example, 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. By bar coding these various items, a variety of significant information can be tracked, such as reagent usage/consumption, how many tests remain for each reagent bottle, open container expiration, closed container expiration, assay values, etc. - The software scheduler may be configured to perform the following steps.
-
- Decide if it is ok to add a new sample at this time or not, and hold off door or multi-loader (random access) if another activity needs to take precedence.
- Minimize the
sample door 18 unavailable effect by adjusting non-kinetic reactions if any, or kinetic reactions that have a broader acceptable window. - Minimize collision effects, and optimize throughput by defining acceptable windows for each kinetic reaction.
- Force analysis to take a predetermined amount of time (stop on time/fixed volume of sample)
- Use predetermined times for each cycle, (acquiring of blood, adding of reagents including mixing, analysis) so all activities can be properly scheduled.
- Take all scheduled sample time windows into effect in determining if it is acceptable to add a new sample to the schedule, and schedule such new sample so that all its activities take place at the predetermined times.
- Take hardware resources and physical hardware collisions into effect in determining if the schedule can be accomplished.
- Using
instrument 10 in combination with the software scheduler disclosed herein, a Time to First Result (TFR) can be less than 15 minutes, with subsequent results reported about every 90 seconds. Throughput can be more than 300 samples per day, and results can be reported much quicker and earlier in the day, so a lab's capacity can be significantly increased. - 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. In contrast,instrument 10 is configured to automatically prepare patient samples incontainment 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. - Prior art processes and systems, with their multiple modules and computer screens, take up between 10 and 13 feet of valuable bench space. In contrast,
diagnostic instrument 10 is compact, measuring only 31 inches wide, inclusive of theautoloader portion 12. The embodiment shown inFIG. 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. - It is contemplated that 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.
- Yet another embodiment of the present disclosure is shown in
FIGS. 12 and 13 , wherein acontainer 110 is equipped with at least one light transmitter 114 (visible inFIG. 13 ) and at least one light receptor 116 (visible inFIG. 13 ). According to the invention,light transmitter 114 directs infrared light intocontainer 110 at a point at which fluid detection is desired. Light receptor 116 is positioned to receive light from thetransmitter 114. - As can be seen in
FIG. 12 , a translucent or transparent container is contemplated, such that infrared light may pass through the container.Container 110 may also have at least onenon-planar side 112 so that light passing through it refracts. In one disclosed embodiment,transmitter 114 and receptor 116 are coupled to a frame 118 that can be positioned around at least a portion ofcontainer 110. - In the illustrated embodiment, 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 fromtransmitter 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. In the case of 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. - Another way in which fluid level may be determined is the amount by which the light refracts as it passes through
container 110. Such light will refract a known amount (i.e. have a predictable refractive index value) when it passes through the container but not through the fluid (i.e. the fluid is below the point of passage of the light). In contrast, when the container is filled with fluid, the light transmitted bytransmitter 114 will refract by a different amount, therefore having a different refractive index value. Because these two values can be distinguished, the infrared light can be used to determine whether the container holds fluid at the selected level. - It is contemplated that
transmitter 114 and receptor 116 may be positioned at a single point on thecontainer 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. However, it may be desirable to have a plurality oftransmitters 114 and receptors 116 positioned at various locations along the height ofcontainer 110, as can be seen inFIG. 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. - Still another embodiment of the present disclosure is shown in
FIGS. 15-16 in the form of adevice coupling 210. Such a coupling may be contrasted, for example, with the prior art coupling shown inFIG. 14 . In the embodiment illustrated inFIGS. 15-16 ,device coupling 210 includes alead screw 212 having a taperedsurface 214 formed on oneend 216 of theshaft 218. For example, taperedsurface 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 infemale portion 220, creating arecess 228.Female portion 220 may be attached to amotor 222, or may be an integral part ofmotor 222. -
Shaft 218 has a threadedhole 224 atend 216 of theshaft 218. In order to joinshaft 218 to female portion 220 (and therefore motor 222), taperedsurface 214 is inserted intorecess 228 offemale portion 220. A screw (not shown) is used to pullshaft 218 intofemale portion 220. Notably, the surface area betweentapered surface 214 andmating 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 twosurfaces - Disassembly of
device 210 is accomplished by loosening the screw and lightly tapping thefirst end 216 ofshaft 218 out of its mated position. Another advantage of the present invention is ease of separation of two expensive components. - In still another embodiment of the invention, a flow cytometer filtration system is shown in
FIG. 17 . As a matter of background, 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. - Accordingly, most flow cytometers require that the samples be pre-filtered, but this does not prevent all clogs. In order to have a more optimal flow cytometer-based automated instrument, this problem should be addressed.
- One method is to have automated back-flushing routines that are activated by some method of automatically detecting clogs. However, 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.
- What is disclosed in
FIG. 17 is aunique filter 300 that prevents clogs. The filter has the following properties: -
- it has
multiple holes 302 that are less than or equal to the cross sectional area of the flow cytometer aperture; - it is located near the sample injector of the flow cytometer in an area where the fluid velocity is very low (typically less than 200 micro liters per minute).
- it can be back flushed at a high fluid velocity;
- the
hole 302 lengths are short (typically less than 300 microns); and - there are multiple holes to reduce overall fluid resistance, reduce fluid velocity through any
single hole 302, and provide multiple pathways in the instance where one or more of the holes is partially blocked.
- it has
- Such a system may be used, for example, with a flow cytometer aperture that forms an equilateral triangle.
- 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 theprobe 26 geometry. As can be seen inFIG. 18 , anillustrative probe 26 has a solidblunt end 310 that can eliminate coring of the septum material.Probe 26 may also have two holes 312 (one of which is visible inFIG. 18 ), such holes being substantially the same size as the internal bore (not shown) ofprobe 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 nearend 310 ofprobe 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 ofprobe 26 due to surface tension can dramatically affect the counting. - Other systems may mix a sample of fluorescent beads with a know concentration with each sample to generate an accurate count. By using the disclosed geometry for
probe 26, the fluorescent bead mixing is not necessary, and the expense and time of this step is eliminated. - While the disclosure is susceptible to various modifications and alternative forms, specific exemplary embodiments thereof have been shown by way of example in the drawings and have herein been described in detail. It should be understood, however, that there is no intent to limit the disclosure to the particular forms disclosed, but on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the disclosure as defined by the appended claims.
- A plurality of advantages arises from the various features of the present disclosure. It will be noted that alternative embodiments of various components of the disclosure may not include all of the features described yet still benefit from at least some of the advantages of such features. Those of ordinary skill in the art may readily devise their own implementations of a diagnostic device probe washer station and method that incorporate one or more of the features of the present disclosure and fall within the spirit and scope of the disclosure.
Claims (21)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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US13/696,277 US20130234053A1 (en) | 2010-05-05 | 2011-05-05 | Diagnostic instrument and flow process |
Applications Claiming Priority (6)
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US33178910P | 2010-05-05 | 2010-05-05 | |
US33179310P | 2010-05-05 | 2010-05-05 | |
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US33179510P | 2010-05-05 | 2010-05-05 | |
US13/696,277 US20130234053A1 (en) | 2010-05-05 | 2011-05-05 | Diagnostic instrument and flow process |
PCT/US2011/035420 WO2011140390A2 (en) | 2010-05-05 | 2011-05-05 | Diagnostic system and components |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/US2011/035420 A-371-Of-International WO2011140390A2 (en) | 2010-05-05 | 2011-05-05 | Diagnostic system and components |
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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 |
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ID=44904488
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US14/836,087 Active 2033-04-15 US11067110B2 (en) | 2010-05-05 | 2015-08-26 | Device coupling for a motor |
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US14/836,087 Active 2033-04-15 US11067110B2 (en) | 2010-05-05 | 2015-08-26 | Device coupling for a motor |
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US (2) | US20130234053A1 (en) |
EP (2) | EP2998745A1 (en) |
JP (2) | JP2013525817A (en) |
KR (1) | KR20130098169A (en) |
CN (2) | CN105044376A (en) |
BR (1) | BR112012028318A2 (en) |
RU (1) | RU2587328C2 (en) |
WO (1) | WO2011140390A2 (en) |
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US11099179B2 (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 |
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Also Published As
Publication number | Publication date |
---|---|
EP2998745A1 (en) | 2016-03-23 |
RU2012152091A (en) | 2014-06-10 |
RU2587328C2 (en) | 2016-06-20 |
JP2013525817A (en) | 2013-06-20 |
JP2016014478A (en) | 2016-01-28 |
EP2567211A2 (en) | 2013-03-13 |
BR112012028318A2 (en) | 2016-11-01 |
KR20130098169A (en) | 2013-09-04 |
WO2011140390A3 (en) | 2012-01-26 |
US11067110B2 (en) | 2021-07-20 |
CN102933948A (en) | 2013-02-13 |
CN102933948B (en) | 2015-06-24 |
EP2567211A4 (en) | 2015-04-01 |
WO2011140390A2 (en) | 2011-11-10 |
US20160053790A1 (en) | 2016-02-25 |
CN105044376A (en) | 2015-11-11 |
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