WO2012150544A1 - Rapid identification of organisms in bodily fluids - Google Patents
Rapid identification of organisms in bodily fluids Download PDFInfo
- Publication number
- WO2012150544A1 WO2012150544A1 PCT/IB2012/052172 IB2012052172W WO2012150544A1 WO 2012150544 A1 WO2012150544 A1 WO 2012150544A1 IB 2012052172 W IB2012052172 W IB 2012052172W WO 2012150544 A1 WO2012150544 A1 WO 2012150544A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- sample
- additive
- cup
- chamber
- sample portion
- Prior art date
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B10/00—Other methods or instruments for diagnosis, e.g. instruments for taking a cell sample, for biopsy, for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
- A61B10/0045—Devices for taking samples of body liquids
- A61B10/0051—Devices for taking samples of body liquids for taking saliva or sputum samples
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
- C12Q1/04—Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/38—Diluting, dispersing or mixing samples
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
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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
Definitions
- the present disclosure relates generally to the field of medicine and more particularly relates to a device that can identify bacterial type above a certain threshold concentration.
- the sputum samples are obtained via bronchoscopy, non- bronchoscopic broncheoaviolar lavage (BAL), closed suction catheter, open suction catheter, or another collection apparatus 16 as indicated in Figure 1 , or from an expectorated sample.
- BAL non- bronchoscopic broncheoaviolar lavage
- the sample is then retained in a container 10 that is often connected to the apparatus 16 through flexible tubing connections 12, 14 or other means.
- Current containers are prone to leakage or spillage, causing concern to the medical personnel involved since the exact microorganisms present are unknown.
- the disconnection of tubing from current containers is also a source for leakage.
- the container holding the sample is transported to the clinical microbiology laboratory for microbial testing and analysis.
- the container is commonly transported in a pneumatic tube system from the ICU to the lab.
- a problem that sometimes arises is that the sample can spill or leak in the pneumatic tubing as it is being transported. This can contaminate the pneumatic system, putting the integrity of other samples transported at risk and requiring a re-sampling of the patient, with its concomitant risks.
- antibiotics have toxic side effects for the patient. For example, some antibiotics can cause harm to the function of the kidneys. Overuse of unnecessary antibiotics can cause "super bugs" and antibiotic resistance, which is a well published problem in health care. The use of these potentially unnecessary antibiotics also incurs a large cost to the hospital.
- the clinician may also isolate a patient that is suspected of having a resistant or highly contagious organism (e.g.; MRSA or TB). There is, of course, an associated cost to so isolate a patient suspected of carrying a concerning organism.
- a gram stain identifies if a bacterial organism is in either the gram negative or gram positive class and the morphology of the bacteria (i.e. cocci, rod, etc .). This allows the clinician to remove antibiotic(s) that affect the class of organisms with which the patient is not infected.
- a gram stain test takes approximately 1 hour to perform, but with transportation time of the sample and the typical lab testing back-log, most ICU clinicians receive the gram stain results in 12-24 hours. During this time a patient is placed on the 3-5 broad spectrum antibiotics mentioned above until the clinician reviews the gram stain results and removes 1-3
- the gram stain is a subjective test because the lab technician is viewing the sample under a microscope to identify the color and location of a staining dye in bacteria cells and tests results could be gram variable, meaning the technician could not identify the bacterial gram class.
- the gram stain procedure generally includes the followings steps: 1 ) place a slide with a bacterial smear on a staining rack, 2) stain the slide with crystal violet for 1 -2 minutes, 3) pour off the stain, 4) flood slide with Gram's iodine for 1-2 min., 5) pour off the iodine, 6) decolorize by washing the slide briefly with acetone (2-3 seconds), 7) wash slide thoroughly with water to remove the acetone - do not delay with this step, 8) flood slide with safranin counter stain for 2 min., 9) wash with water, 10) blot excess water and dry by hand over (Bunsen) flame.
- Microbial specificity identifies the exact organism(s) that are causing the infection and the concentration of that
- the third round of microbial data that a physician receives is call antibiotic sensitivities. These results are obtained in 48-72 hours and require testing the cultured sample against known antibiotics to determine the resistance pattern of the organism. Once it is known what antibiotics the organism is sensitive to or will kill the organism(s), the clinician can change to one or at least fewer targeted antibiotic to treat the infection.
- the present disclosure provides a sample isolation and on-demand testing device (equivalently termed “the device”).
- the device includes: a receptacle, termed “sample cup”, or “cup” to retain a sample; other subsequently described components for on-demand testing of a small portion of the collected sample, equivalently termed “sample portion” or “portion of the sample”; retention of the remaining sample in the cup for optional additional analysis.
- the on-demand test provides relatively immediate information about aspects of the sample, e.g. presence of microbes, chemistry, nutritional condition, presence of contaminants.
- One exemplary on-demand test would determine the presence of gram negative bacteria, gram positive bacteria, both gram negative and gram positive bacteria, or no bacteria detected.
- a non-bronchoscopic or bronchoscopic collection apparatus may be used to obtain a sample, e.g. sputum, from the patient.
- a sample e.g. sputum
- the collection apparatus obtains the sample below the corina and ideally in the third generation lung lobe.
- a sample is deposited in the cup of the inventive device.
- the collection apparatus is integrated with the device.
- test and all the components and additives needed to complete the test are desirably completely integrated into the device so no secondary processing is needed. If other steps, such as mixing and pipetting additives were needed, this test would not be practical to perform at the bedside.
- This device could also be used as a screening tool to test a patient upon admittance to the hospital or admission to a specific unit of the hospital to determine if the patient is colonized with a clinically significant concentration of bacteria. This information would allow the clinician to isolate or treat a patient before clinical signs of infection are obvious. This early information could also help a hospital determine if a patient obtained a hospital acquired infection (HAI) or already had an infection prior to admission, called a community acquired infection (CAI) for public reporting and billing purposes.
- HAI hospital acquired infection
- CAI community acquired infection
- an additive e.g. to lyse
- the additive and sample portion are desirably well mixed and this could be activated and timed by a mechanical button or slide or via an additional button push, passive and or active valve, mechanical motor, or other means. Such mixing may also take place by simultaneously directing the sample portion and additive through a common port to the assay assembly. Once the optional additive and the sample portion are mixed, they are conducted to directly contact the assay assembly.
- the device allows for adequate exposure of the sample portion and any necessary mixed additive to the assay assembly for a pre-determined period of time to ensure migration of some of the sample portion with mixed additive through the assay assembly.
- An example of such a time period is desirably about 15 minutes or even less, though preferably less than 30 minutes.
- a detector may sense a change in a colorimetric, florescent, magnetic or other expression of a test result in the assay assembly.
- the detector outputs the result to a display for external visualization.
- An example of a detector that is suitable for use in the device is an optical detector that scans for changes in reflected light at specific intensity ranges.
- the scanned intensity of the test expression is an important factor in determining the output to the display; when a scanned intensity is outside a specific range, such a detector is programmed to prevent the detector from outputting erroneous results, e.g. slight cross reactivity of the test.
- the display is important so the user (e.g. nurse or respiratory therapist) has no subjectivity in interpreting the test results.
- this device allows the clinician to potentially prescribe fewer initial antibiotics to the patient, thus reducing toxicity for the patient, decreasing antibiotic resistance, and saving the hospital costs on unnecessary antibiotics.
- Figure 1 is a drawing of a prior art sample collection container.
- Figure 2 is a representation of a lateral flow assay strip, illustrating the various layers and components that are used to construct the strip.
- Figure 3 is a drawing of an embodiment of a sample cup and an assay assembly according to the disclosure where the assembly performs one test.
- Figure 4 is an exploded view of the embodiment of Figure 3.
- Figures 5A, 5B and 5C are drawings of different ways in which the results of the disclosed test may be displayed.
- Figure 6 is a drawing of an embodiment of a sample cup and assay assembly according to the disclosure where the assembly performs two tests.
- Figure 7 is an exploded view of the embodiment of Figure 6.
- Figures 8A and 8B show a side view (8A) and a top view (8B) of another embodiment according to the disclosure that shows a different orientation of the components of the device from those shown in Figures 3 and 6.
- Figures 9A and 9B are alternate views of Figure 8 showing a cutaway side view (9A) and a top view (9B) of the device prior to use.
- Figure 10 is a close up view inside a portion of the cup showing an opening to the chamber from the cup and ribs that may filter out large particles.
- Figures 1 1A, 1 1 B and 1 1 C are alternate views of Figure 8 showing a cutaway side view (1 1 A), a top view (1 1 B) of the device at the position where it is almost completely activated and an intermediate position (1 1 C).
- Figures 12A, 12B and 12 C show partial top (12A) and side cutaway views of an embodiment of the device.
- the device is not activated and the chamber and cup are in fluid communication.
- the device is activated and fluid has been moved by a piston to an assay assembly via an outlet port.
- Figures 13A and 13B are partial top (13A) and side (13B) cutaway views of an embodiment with a piston and a check valve.
- Figure 13C shows the device activated but prior to the puncturing of the additive foil packet.
- Figure 13D shows the device when it is almost completely activated and the foil packet has been punctured.
- Figures 14A, 14B and 14C are partial top (14A, 14C) and side (14B) cutaway views of an embodiment without the containment structure for the additive present.
- Figure 14C shows the device prior to activation and 14A and 14B show the device after activation.
- Figures 9 and 1 1 - 14 show depictions of the device from the top without the assay assembly shown.
- the mechanical components of this device are required to contain a sample, separate a portion of the sample, add an optional additive to the sample portion, optionally wait a specified delay time, and then conduct the sample portion and additive to the assay assembly. Inherent in all the steps will be sealing to provide segregation of fluids and prevention of exposed biohazards. Additionally, the product desirably has a 1 to 2 year shelf life (dependent on the assay assembly), which requires solutions for seal performance and prevention of premature fluid migration. Finally, the clinician prefers to perform a single action to activate the device, and not more than two actions.
- additives may be added to aid in lysis of the bacteria cells, for pH control and the like.
- Possible additives include bacteria lysis reagents, buffers, detergents, tris-buffered saline, bovine serum albumen, pH modifiers and combinations thereof.
- Containment of the additive to mix with the sample portion requires intentional design considerations to address permeability of these contained additives for up to a 2 year shelf life. Minimizing leakage of such additives is important for volumetric accuracy (example: controlling a 4:1 additive/sample ratio) and also limiting water migration and evaporation.
- a film or foil laminate packet is one way to contain such additives. A packet, however, is difficult to adequately open so its contents can be fully emptied.
- Venting issues associated with transfer of the packet's contents can also be problematic (e.g. using an elastomeric bladder).
- a check valve to seal an opening that ports to a confining structure around such additives not expected to provide an adequate permeability barrier.
- One approach is to use a fluid impermeable piston on each end of a relatively thick-walled cylindrical shell to store the additive. A rough estimate indicates that a 21 ⁇ 2 mm polypropylene or polyethylene confining wall around the additives could adequately maintain them over 3 years.
- a mechanical timer could be a clock type device (e.g., windup mechanism found in toys) or a restricted hydraulic/dampening feature (e.g., a viscous fluid flowing through an orifice).
- An example of an electronic timer is a microprocessor that is incorporated in the analysis module, and control of the timing is handled by software.
- the additives may be incompatible or may degrade rapidly when mixed, so a single confining structure for both additives when mixed together may compromise shelf life preferences.
- a piston may be designed to deliver to the sample portion first one additive and then a second additive (or third, etc.). This sequential delivery of additives would avoid the problem of additive incompatibility.
- an alternative to a confining structure for an additive is to apply the additive directly to a part of the assay assembly.
- the additive could be applied as a liquid to, for example, a lateral flow assay strip, and allowed to dry. The dried residue of the additive would contact the sample portion when the sample portion was delivered and could then function in the same manner as additive that is mixed with the sample portion prior to contacting the assay assembly.
- One embodiment involves movement of a piston to draw the sample portion into contact with the additive. If a film or foil seal is used to contain the additive, puncturing and venting must be integrated into the sequence. Additionally, establishing positive sealing during the transport of the sample portion is important.
- the actuation of the piston could be driven by a small motor (with a lead screw or rack and pinion), could be from releasing a spring, or could be by a manual push of the plunger handle.
- a permeable membrane may also be needed on the chamber to allow venting (but not allow liquid to escape).
- exemplary assay assemblies include an enzyme-linked immunosorbent assay (ELISA) test, lateral flow assay, or flow through assay that may test for specific bacteria
- the ELISA test may desirably be a lateral flow assay test strip (LFA) that is an immunoassay (antibody detection) utilizing a visual (colorimetric) signal.
- LFA employs a threshold detection system with a "positive" result when bacteria are above a 10 3 -10 4 colony forming units/ milliliter (cfu/ml). Colloidal gold, 40nm, may be used as the detection label. Multiple analytes are used depending on the bacteria class; lipoteichoic acid (LTA) for Gram Positives and Lipopolysaccharide (LPS) for Gram Negatives.
- LTA lipoteichoic acid
- LPS Lipopolysaccharide
- the LFA can utilize multi-line detection with between 2-4 test lines.
- the LFA usually includes one control line and may be direct antigen binding or a sandwich complex.
- a suitable additive is a running buffer consisting of tris-buffered saline with detergents (Tween 20) and non-specific proteins (bovine serum albumin or BSA) may be incorporated in the device.
- the detection and control lines are desirably read with reflectance-based measurements.
- the total time to run the test is desirably approximately fifteen minutes and desirably less than 30 minutes.
- the LFA desirably has the specifications given in Table 1.
- the item numbers in the left hand column of Table 1 may be found in Figure 2, which shows a possible configuration for a lateral flow assay test strip. Table 1
- Sample Pad - may be eliminated in
- Conjugate Pad - may also receive
- Antibodies are commercially available.
- the LFA will desirably be housed in a plastic enclosure that may be an integrated piece of the device. Fluid communication through the LFA is achieved through the physical overlap of discreet membranes. The physical contact between membranes may be maintained through plastic pinch points that may be part of the housing assembly. The sample may require additional processing steps prior to addition contact with the LFA. This processing could include the addition of bacteria lysis reagents, detergents, and other additives.
- An alternate approach to processing the sample portion may include running the test with whole-cell, live bacteria. In this case an additive and mixing time are not needed and the sample only needs to be metered out of the cup in a known quantity prior to addition to the assay assembly.
- Electronics components found suitable for use in the device include a
- microprocessor display 40, LEDs 22, detector 32, battery 36, and miscellaneous passive components (resistors and capacitors) and can all be located or attached to a common circuit board 34 .
- display 40 LEDs 22, detector 32, battery 36, and miscellaneous passive components (resistors and capacitors) and can all be located or attached to a common circuit board 34 .
- miscellaneous passive components resistor and capacitors
- Microprocessor The microprocessor runs the software that controls the LED 22, display 40, and detector 32. If an electronic means of controlling the timing of sample flow to the assay assembly is needed, the microprocessor will also control that function.
- the main characteristics are program memory, data memory, display control lines, LED control lines, and detector inputs.
- the microprocessor is located on the circuit board 34.
- Display 40 - The display's function is to provide information to the user on device status and assay assembly status, including indications of activity, error, gram positive, gram negative, and no bacteria present.
- the display can be a standard Twisted Nematic (TN) type liquid crystal display of size equivalent to those found in the pregnancy test products. The display could be driven directly by output pins on the microprocessor.
- TN Twisted Nematic
- LED 22 The Light Emitting Diode provides illumination to the assay assembly. It must provide sufficient intensity for the photo-detectors to have sufficient signal-to- noise ratio to detect the indicators on the assay assembly.
- a suitable commercial LED is the SMT660 part.
- a suitable commercial photo-detector is the Advanced Photonix PDB-C154SM.
- Battery 36 The battery must supply not only enough capacity to operate the "sleeping" device over its two plus years of shelf life, it must then supply sufficient current at a high enough voltage to drive the LED to its desired brightness.
- Small, long-life batteries lithium coin cells
- This internal resistance manifests itself as a significant drop in voltage when large amounts of current are supplied to LED's or motors.
- Motor A motor may optionally be used to activate the wetting of the assay assembly. If so, this motor will be a small inexpensive DC motor such as commonly used in small toys.
- Printed Circuit Board 34 The printed circuit board may be a two-sided board of approximately ⁇ 2" x ⁇ 1 ⁇ 2". The attachment of the LCD will vary with the chosen attachment method. This could be pinned, elastomeric (Zebrastrip), or heat seal.
- the operation of the device can be divided into several phases. These are manufacturing, shelf life, monitoring, display results, and end-of-life.
- the device can provide information needed by the contract manufacturer to determine if the device was manufactured correctly. This may include turning on all the display icons, flashing the LED, etc.
- shelf life the device is in a very low power mode waiting for an input to indicate it is time to process the assay assembly. Once the input wakes up the device, it must activate the display and periodically turn on the LED and process results. This desirably occurs for about 15 minutes at which time the device transitions to the results phase.
- the display results phase the device shows the results on the display but no longer is running the detection circuitry. This is a low power mode that can last for considerable period of time. At some point, the device can transition to the end-of-life phase where it turns off the display.
- Table 2 below shows an estimate of the energy needed to run the device across its operating life. It is assumed that the LED is operated at a 10% duty cycle (on for 100 ms per second) and is operated at 10 mA. It is also assumed the microprocessor is run at 1 MHz or less to reduce power. These assumptions result in a needed battery capacity of 30 mA-Hrs. This value can be reduced considerably by proper design of testing at manufacture (approximately 40% of needed capacity). In addition, the battery should be able to supply 10 mA for at least 100 ms without the voltage dropping below usable values (-2.4V).
- the capacity of lithium coin cells is rated assuming a cutoff voltage of 2.0 V. Our device will need to operate above -2.4V (due to effect of pulse current) so the battery's capacity needs to be de-rated by 30% to account for this difference.
- the best choice for a lithium coin cell is the CR2025. It has a 160 mA-Hr capacity (derated to 1 12) and is capable of supplying pulse currents needed by the LED.
- Lithium coin cells have a high internal resistance which limits the current delivered by the battery and may prevent them from driving a motor.
- AAA-sized alkaline cells are a likely replacement for use with a motor. They can supply large amounts of current without significant drop in voltage.
- Example embodiment 1
- This embodiment utilizes one additive 20, one assay assembly 122, in this case a lateral flow assay (LFA) strip, and requires the user to manually apply effort to the device to move the sample, sample portion, and additive 20 to the appropriate positions within the device.
- Figure 3 shows a possible illustration of the embodiment.
- Figure 4 demonstrates a possible exploded assembly view showing key components of the device. Movement of one of the pistons draws the sample portion into contact with the additive 20. The movement of this piston could be the direct input of the user; e.g. lifting a plunger handle, or it could be driven by a small motor (with a lead screw or rack and pinion).
- the additive 20 is confined in a housing 101 of any shape designed for mixing with the sample portion.
- “pushing" the piston means that the piston is moved downwardly towards the cup 102 and “pulling” the piston means that the piston is moved upwardly away from the cup 102.
- the medical user i.e. a clinician, acquires a sample via current practice and the sample is deposited in the cup 102.
- the clinician may gently shake the device as needed to help make the sample homogeneous in the sample cup 102.
- the clinician will pull the handle 12 up, moving the upper piston 14 upwards and sucking the lower piston 16 with it as well as the additive 20 that is intitially confined in a space between the upper piston 14 and lower piston 16.
- the space between the pistons defines the chamber 100.
- the movement of the lower piston 16 allows electrical contacts to touch, "waking up” the electronics.
- the lower piston 16 hits a hard stop at the same time the upper piston 14 moves past a check valve 18 inlet that it had been sealing closed.
- the suction force of the movement of the pistons pulls the sample portion up a conduit 13 from the bottom of the cup 102 through the check valve 18 and into the chamber 100 that confines the additive 20.
- the clinician may gently shake the device to further mix the sample portion and additive 20.
- the clinician watches the display 22 until an indication is provided that the handle 12 can be depressed.
- the lower piston 16 When the handle 12 is pushed down by the clinician, the lower piston 16 is driven down until an outlet port 24 is uncovered, allowing the sample portion and additive 20 to flow into a well 26 where it comes in contact with the assay assembly 122.
- a port (not shown) is provided to allow any trapped air, but not liquid, to escape.
- a test result is displayed when the test is complete.
- the display can be as simple as LED lights or it can be the LCD screen display 22.
- the display via the LCD screen may show the results of the test per the examples shown in Figures 5A, 5B and 5C but any option is appropriate.
- the examples of Figures 5 indicate that the sample portion is gram negative, gram positive, both or neither over a set threshold amount, and includes a status if there is an error with the system. An error status can occur when the user fails to initiate a step within a given time period or if the sample fails to activate the 'control line' on the assay assembly.
- Figures 5A, 5B and 5C different ways of expressing the results are shown. Each figure indicates a gram positive result on the far left, followed by gram negative, both gram positive and negative present, neither gram positive nor negative present, and, on the right, an error signal.
- Example embodiment 2 Example embodiment 2:
- the second embodiment to be described is more complicated and requires the incorporation of two tests within the assay assembly or two assay assemblies 122, one for Gram Positive (GP) and one for Gram Negative (GN), and two liquid additives 20, one for each assay.
- Figure 6 is a drawing of an embodiment of such features integrated into an exemplary device.
- Figure 7 is an exploded view of the embodiment of Figure 6.
- the user acquires a sample and manipulates the device, similar to Embodiment 1.
- the clinician will pull the handles 12 up, moving the upper pistons 14 upwards, sucking the additives 20 and lower pistons 16 with them.
- the handles 12 may be moved simultaneously or sequentially. Subsequent actions within the device proceed in the same manner as described for Embodliment 1 : one set of actions proceeds for movement on one of the handles 12; another set of actions proceed for movement of the other handle 12.
- an alternative to the vertical orientation of embodiments 1 and 2 is a horizontal orientation.
- the check valve can be located in the bottom of the cup, for example in a well, to minimize entrapped air and sample volume and avoid starvation/clogging of the conduit 13 that the sample portion follows to the assay assembly 122. Air trapped must be managed to ensure the correct amount of fluid is delivered to the assay assembly 122 while remaining liquid tight. There will be air trapped above the two ports and some additional air may come in to replace liquid vapor losses.
- Figure 8A is a top view of the device and Figure 8B is a side perspective view.
- This device includes two horizontal containment structures, generally in the form of side-by-side cylinders; one for providing the sample chamber 100 and the second a housing 101 to initially confine an additive 20 and/or additives.
- the cup 102 may be generally cylindrical.
- the sample chambers 100 and housing 101 are shown generally perpendicular to the cup 102, though this geometrical arrangement is not required. In the start position, a portion of the sample chamber 100 is open to the cup
- Sample collection may be done in one step or may be done serially.
- the sample(s) that is introduced into the cup 102 is allowed to flow and mix
- a filtration media (e.g. ribs) 1 18 may be placed around the sample chamber 100 to enable a gross level of filtering of large particles and high viscosities.
- Figure 10 depicts a suitable arrangement of ribs that serve as the filtration media around the chamber 100.
- a foam pad material may also be placed within a well 1 1 1 to further filter the sample portion and any additive 20 and/or additives. .
- the chamber 100 is open to the cup 102, where the opening may be via two entrances, multiple entrances, or even an unbounded entrance. Desirably, the chamber 100 is open to the cup 102 at the top and bottom so that sample may flow into the chamber 100 freely. Having multiple open pathways for the sample to enter the chamber 100 ensures filling of the chamber and helps prevent formation of an air pocket or pockets within the chamber.
- the chamber 100 is positioned between movable walls respectively joined to movable pistons 103, 104. These pistons are in communication with each other and also with an activation button (push button) 105. O-rings 107 or other means may be used to maintain a liquid seal between the pistons 103, 104 and the surrounding walls. It should be noted that in this and the following embodiments, “pushing" the button 105 means that the button 105 is moved towards the cup 102 and “pulling" the button 105 means that the button 105 is moved away from the cup 102.
- the housing 101 may serve as a movable piston or there may be a separate piston 106 which is also in communication with the push button 105.
- the additive 20 and/or additives are located in this housing 101 between the piston 106 and the outlet port 1 10 to the assay assembly or assemblies 122.
- the additive 20 and/or additives can be contained in blister packs or the like.
- the additive 20 and/or additives may be located inside the piston 106 and sealed in a puncture-able package.
- the package may be made from or sealed with a film or foil which may desirably be metallic to reduce permeability issues (e.g. leakage).
- the device may be activated by the user pushing the button 105 in completely. With this one motion the following steps occur within the chamber 100 and housing 101 :
- the additive piston 106 hits the end of its stroke where the package is punctured by contact with a point 1 12 and the additive 20 and/or additive content is pushed towards the well 1 1 1 through the exit port(s) 1 10.
- Both the sample portion and the additive 20 exit their respective chambers 100, 101 via connected, common port or ports 1 10 and come together, desirably mixing effectively, prior to reaching assay assembly 122 and desirably prior to the well 1 1 1
- chamber 100 and housing 101 are relatively completely evacuated by the movement of the appropriate pistons, allowing all the fluid to be injected to the well 1 1 1 (Figure 1 1 A).
- Figure 9B shows the device in cross section prior to activation
- Figure 1 1 B shows the device in cross section almost completely activated.
- Figure 1 1 B shows the device prior to complete activation for clarity.
- Effective mixing is enhanced by desirably having both the sample portion and additive 20 and/or additives start and stop flowing though the common port 1 10 at the same time. Implicit in proper design of the device is pre-determining appropriate volume and ratio of sample portion to additive 20 and/or additives for use by the assay assembly or assemblies. Piston stroke lengths and internal dimensions of the sample chamber, the containment structure, associated conduits, ports, well, etc. must also be properly designed.
- the sample portion and additive 20 and/or additives can be delivered to more than one assay assembly 122 depending on test requirements.
- the inclusion of the well 1 1 1 can interface with more than one assay assembly.
- Each assay assembly 122 can each have a port coming from the well 1 1 1 . It is believed that the device can apply a sufficient amount of sample portion with additive 20 and/or additives to the assay assembly or assemblies 122 even when the device is activated in a non-neutral position; e.g. a 40 degree tilt. This is accomplished by sizing the sample portion, chamber 100, housing 101 , etc. appropriately to obtain sufficient volume of the sample portion with additive 20 and/or additives in the well 1 1 1.
- This embodiment is similar to Embodiment 3 except this embodiment has the ability to actively fill the sample chamber 100 with a sample portion from the cup 102. This is accomplished with the trialing piston 104 being initially placed adjacent to the leading piston 103 prior to user activation as shown in Figures 12 A and 12B.
- the additive 20 is present in a housing 101.
- Figure 12A shows a top view of the device with the trailing piston 104 adjacent the leading piston 103.
- the additive 20 is also shown.
- the same position is shown in a cutaway side view in Figure 12B with the pistons 103, 103 adjacent to each other and the exit port 1 10 visible.
- the first step of user activation is to pull out on the button 105 as shown in Figure 12C.
- FIG. 13A shows a bottom view of the device showing the trailing piston 104 and the first check valve 126.
- the sample chamber 100 does not contain any sample and is separated from the cup 102 by the first check valve 126 that is in fluid communication with the cup102 and only allows a sample portion to flow into the chamber 100 when the piston 104 is pulled back ( Figure 13B).
- Figure 13C When the piston 104 is pulled back a sample portion is drawn into the chamber 100 from the cup 102 through the first check valve 126 as shown in Figure 13C.
- a second check valve 128 only allows an isolated sample portion to flow out of the chamber 100 to the exit port 1 10 as illustrated in Figure 13D.
- the trailing piston 104 moves outward and the sample portion from the cup 102 flows through the first check valve 126 and fills the sample chamber 100, with which it is in fluid communication, because of the vacuum generated between the pistons.
- the first check valve can be a duckbill valve, umbrella valve, spring loaded valve or any another type of one-way valve that operates similarly.
- the second check valve 128 may any of those suitable for the first check valve 126 and may also be a simple plug or ball that is able to pop open when a pressure is generated when the trailing piston 104 advances forward.
- the additive 20 is present in a housing 101.
- FIG. 14A shows a cutaway top view of the device and Figure 14B shows a cutaway side view in the initial position prior to activation.
- the trailing piston 104 moves outwardly, generating a suction that pulls a sample portion into the chamber 100 through the first check valve 126 from the cup 102 ( Figure 14A).
- the sample portion mixes with the additive 20 already in the chamber 100 as it enters.
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Abstract
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Claims
Priority Applications (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
MX2013012328A MX2013012328A (en) | 2011-05-05 | 2012-05-01 | Rapid identification of organisms in bodily fluids. |
BR112013027497A BR112013027497A2 (en) | 2011-05-05 | 2012-05-01 | rapid identification of organisms in body fluids |
AU2012251368A AU2012251368A1 (en) | 2011-05-05 | 2012-05-01 | Rapid identification of organisms in bodily fluids |
CN201280021565.7A CN103547221A (en) | 2011-05-05 | 2012-05-01 | Rapid identification of organisms in bodily fluids |
EP12722883.1A EP2704637A1 (en) | 2011-05-05 | 2012-05-01 | Rapid identification of organisms in bodily fluids |
KR1020137029218A KR20140016353A (en) | 2011-05-05 | 2012-05-01 | Rapid identification of organisms in bodily fluids |
CA2832544A CA2832544A1 (en) | 2011-05-05 | 2012-05-01 | Rapid identification of organisms in bodily fluids |
RU2013152689/14A RU2013152689A (en) | 2011-05-05 | 2012-05-01 | DEVICE FOR TESTING PHYSIOLOGICAL LIQUID SAMPLES |
JP2014508907A JP2014513801A (en) | 2011-05-05 | 2012-05-01 | Rapid identification of organisms in body fluids |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201161482773P | 2011-05-05 | 2011-05-05 | |
US61/482,773 | 2011-05-05 | ||
US201261596838P | 2012-02-09 | 2012-02-09 | |
US61/596,838 | 2012-02-09 | ||
US13/459,576 US20120282681A1 (en) | 2011-05-05 | 2012-04-30 | Rapid Identification of Organisms in Bodily Fluids |
US13/459,576 | 2012-04-30 |
Publications (1)
Publication Number | Publication Date |
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WO2012150544A1 true WO2012150544A1 (en) | 2012-11-08 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IB2012/052172 WO2012150544A1 (en) | 2011-05-05 | 2012-05-01 | Rapid identification of organisms in bodily fluids |
Country Status (11)
Country | Link |
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US (1) | US20120282681A1 (en) |
EP (1) | EP2704637A1 (en) |
JP (1) | JP2014513801A (en) |
KR (1) | KR20140016353A (en) |
CN (1) | CN103547221A (en) |
AU (1) | AU2012251368A1 (en) |
BR (1) | BR112013027497A2 (en) |
CA (1) | CA2832544A1 (en) |
MX (1) | MX2013012328A (en) |
RU (1) | RU2013152689A (en) |
WO (1) | WO2012150544A1 (en) |
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WO2014132150A1 (en) * | 2013-02-27 | 2014-09-04 | Kimberly-Clark Worldwide, Inc. | Rapid identification of organisms in bodily fluids |
US8974399B2 (en) | 2010-10-15 | 2015-03-10 | Avent, Inc. | System and method for sampling device for bodily fluids |
WO2020058782A1 (en) | 2018-09-21 | 2020-03-26 | Foss Analytical A/S | Lateral flow assay device and analyser |
RU2797017C2 (en) * | 2018-09-21 | 2023-05-30 | ФОСС Аналитикал А/С | Lateral spread analysis device and analyser |
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US9113850B2 (en) * | 2010-08-20 | 2015-08-25 | Reflex Medical Corp. | Saliva collection device |
US9907707B2 (en) | 2011-06-03 | 2018-03-06 | The Procter & Gamble Company | Sensor systems comprising auxiliary articles |
EP2904394A4 (en) * | 2012-10-05 | 2016-11-16 | Verax Biomedical Inc | Multi-analyte assay |
HRP20211588T1 (en) | 2012-11-13 | 2022-01-07 | Premier Biotech, Inc. | Screening device for analysis of saliva |
GB2578841B (en) | 2013-08-08 | 2020-09-30 | Procter & Gamble | Sensor systems for absorbent articles comprising sensor gates |
DE102014001386A1 (en) * | 2014-02-01 | 2015-08-06 | Dräger Safety AG & Co. KGaA | Sample preparation and test system |
CN106290819B (en) * | 2015-05-27 | 2018-06-19 | 艾博生物医药(杭州)有限公司 | A kind of device for mixing at least two substances |
US10285871B2 (en) | 2016-03-03 | 2019-05-14 | The Procter & Gamble Company | Absorbent article with sensor |
MX2018015889A (en) * | 2016-06-29 | 2019-05-27 | Click Diagnostics Inc | Devices and methods for the detection of molecules using a flow cell. |
EP3787583A1 (en) | 2018-05-04 | 2021-03-10 | The Procter & Gamble Company | Sensor devices and systems for monitoring the basic needs of an infant |
US11051996B2 (en) | 2018-08-27 | 2021-07-06 | The Procter & Gamble Company | Sensor devices and systems for monitoring the basic needs of an infant |
EP4085149A4 (en) | 2020-01-03 | 2024-03-06 | Visby Medical Inc | Devices and methods for antibiotic susceptibility testing |
US11914131B1 (en) * | 2020-08-16 | 2024-02-27 | Gregory Dimitrenko | Optical testing system for detecting infectious disease, testing device, specimen collector and related methods |
KR102483098B1 (en) * | 2022-04-06 | 2023-01-02 | 남택신 | Sample insertion type diagnostic kit |
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- 2012-05-01 WO PCT/IB2012/052172 patent/WO2012150544A1/en active Application Filing
- 2012-05-01 KR KR1020137029218A patent/KR20140016353A/en not_active Application Discontinuation
- 2012-05-01 AU AU2012251368A patent/AU2012251368A1/en not_active Abandoned
- 2012-05-01 CN CN201280021565.7A patent/CN103547221A/en active Pending
- 2012-05-01 EP EP12722883.1A patent/EP2704637A1/en not_active Withdrawn
- 2012-05-01 CA CA2832544A patent/CA2832544A1/en not_active Abandoned
- 2012-05-01 BR BR112013027497A patent/BR112013027497A2/en not_active IP Right Cessation
- 2012-05-01 JP JP2014508907A patent/JP2014513801A/en active Pending
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Also Published As
Publication number | Publication date |
---|---|
AU2012251368A1 (en) | 2013-11-21 |
RU2013152689A (en) | 2015-06-10 |
US20120282681A1 (en) | 2012-11-08 |
MX2013012328A (en) | 2013-11-01 |
EP2704637A1 (en) | 2014-03-12 |
CN103547221A (en) | 2014-01-29 |
CA2832544A1 (en) | 2012-11-08 |
KR20140016353A (en) | 2014-02-07 |
JP2014513801A (en) | 2014-06-05 |
BR112013027497A2 (en) | 2017-01-10 |
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