FILTERING AND METERING

Cross-Reference to Related Application

[0001] This application claims priority to U.S. Provisional Patent Application No. 62/897,190, filed September 6, 2019, the disclosure of which is incorporated by reference herein in its entirety.

Technical Field

[0002] This application relates generally to systems, devices, and methods for collecting a sample and for processing the sample in an infection detection system.

Background

[0003] Patient exposure to health care environments elevates risk of systemic and/or local infections caused by commensal microorganisms. Infection risk is particularly elevated during the use of external communicating medical devices. There is accordingly a need for systems, devices, and methods for rapidly collecting, identifying, quantifying, and characterizing causative microorganisms associated with infections.

[0004] For any Point-of-care diagnostic system, the ability to collect the required amount of sample and transfer that sample to the testing system is critical. Existing methods that are used to collect biological samples for laboratory testing may collect too much sample as these methods are generally tailored to suit laboratory testing equipment utilized in central testing facilities. For example, venous blood collected for culture and testing can be as much as 20ml of blood. Such a large sample is not amenable for a Point-of-care testing system. There is therefore the need to take these large sample volumes/sizes collected using conventional sample collection methods and reduce them to appropriate sizes without any appreciable loss in biological signal or target of interest.

Summary

[0005] The present inventors recognize that there is a need to improve one or more features of infection detection systems and methods. This invention proposes various methods to transfer sample in liquid form from a syringe or vacuum collection tube to a microfluidic cartridge. In some embodiments of the invention, the transfer mechanism simultaneously meters the transferred sample to a specific volume during the transfer to the microfluidic system. These embodiments simplify the steps of use for the clinicians by eliminating the need for manual laboratory equipment for dilution methods and centrifuging of the samples.

[0006] According to aspects of the invention, an infection detection system includes a sampling device configured to collect a whole blood sample containing a pathogen target, a meter configured to be removably connected to a portion of the sampling device to meter a predetermined amount of the whole blood sample, a sample processor comprising aNASBA fluidic network configured to be in fluid communication with the meter to receive the whole blood sample. The NASBA fluidic network includes an enzyme and a primer for amplifying a predetermined genetic sequence in the pathogen target and a beacon that is configured to attach to the predetermined genetic sequence in the pathogen target. The infection detection system further includes an analytical instrument configured to identify the beacon when the beacon is attached to the predetermined genetic sequence in the pathogen target to signal a presence of the pathogen target.

[0007] The infection detection system further includes a filter configured to filter the whole blood sample.

[0008] The infection detection further includes a lysing chamber configured to lyse the whole blood sample into a lysate.

[0009] The sampling device comprises a first tube and second tube, the first tube comprising the portion of the sampling device and the second tube comprising the meter, and the first tube and the second tube are removably coupled via luer fittings.

[0010] The sampling device further comprises a duckbill umbrella valve and a piston disposed within the second tube.

[0011] The meter comprises a housing and a removable metered sample well (700) disposed within the housing, the housing being configured to connect to the portion of the sampling device to draw the whole blood sample from the sampling device, and the metered sample well (700) being configured to meter the predetermined amount of the w hole blood sample.

[0012] The metered sample will is configured to be removed from the housing and connected to the sample processor and to fluidly communicate the predetermined amount of the whole blood sample to the sample processor.

[0013] The primer includes any one or more of oligonucleotide sequences SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 41, SEQ ID NO: 42,

SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 73, SEQ ID NO:

74, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 85,

SEQ ID NO: 86, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 93, and SEQ ID NO: 94.

[0014] The beacon includes any one or more of oligonucleotide sequences SEQ ID NO: 3, SEQ ID NO: 7, SEQ ID NO: 11, SEQ ID NO: 15, SEQ ID NO: 19, SEQ ID NO: 23, SEQ ID NO: 27, SEQ ID NO: 31, SEQ ID NO: 35, SEQ ID NO: 39, SEQ ID NO: 43, SEQ ID NO: 47, SEQ ID NO: 51, SEQ ID NO: 55, SEQ ID NO: 59, SEQ ID NO: 63, SEQ ID NO: 67, SEQ ID NO: 71, SEQ ID NO: 75, SEQ ID NO: 79, SEQ ID NO: 83, SEQ ID NO:

87, SEQ ID NO: 91, and SEQ ID NO: 95.

[0015] The infection detection system comprising a lysis solution for lysing microorganisms in the whole blood sample, the lysis solution comprising 2 mM to 16 mM of a Quanidinium thiocyanate/guanidine thiocyanate; 20 mM to 160 mM of a Tris HCL, pH 8.5;

6 pM to 48 pM of a Magnesium chloride; 35 pM to 280 pM of a Potassium chloride; and 0.1% v/v to 1.0% v/v of an octylphenoxypolyethoxyethanol.

[0016] Further aspects of the invention include a method of detecting an infection using the infection detection system. The method including collecting the whole blood sample containing the pathogen target, metering the predetermined amount of the whole blood sample in the meter, removing the meter and connecting the meter to the sample processor, amplifying the predetermined genetic sequence in the pathogen target, attaching the beacon to the predetermined genetic sequence of the pathogen target and exciting the beacon attached to the pathogen target to signal the presence of the pathogen target.

[0017] The method further including lysing the whole blood sample using a lysis solution comprising: 2 mM to 16 mM of a Quanidinium thiocyanate/guanidine thiocyanate;

20 pM to 160 pM of a Tris HCL, pH 8.5; 6 pM to 48 pM of a Magnesium chloride; 35 pM to 280 pM of a Potassium chloride; and 0.1% v/v to 1.0% v/v of an octylphenoxypolyethoxyethanol.

[0018] There are, of course, additional aspects of the various embodiments of the invention disclosed herein that will be described below and which will form the subject matter of the claims. In this respect, before explaining at least one aspect of the invention in detail, it is to be understood that the invention is not limited in its application to the details of construction and to the arrangements of the components set forth in the following description or illustrated in the drawings. The invention is capable of aspects in addition to those described and of being practiced and carried out in various ways. Also, it is to be understood that the phraseology' and terminology employed herein, as well as the Abstract, are for the purpose of description and should not be regarded as limiting.

[0019] As such, those skilled in the art will appreciate that the conception upon which this invention is based may readily be utilized as a basis for the designing of other structures, methods, and systems for carrying out the several purposes of the invention. It is important, therefore, that the claims be regarded as including such equivalent constmctions insofar as they do not depart from the spirit and scope of the invention.

Brief Description of Drawings

[0020] In order that the invention may be readily understood, aspects of the invention are illustrated by way of examples in the accompanying drawings; however, the subject matter is not limited to the disclosed aspects.

[0021] FIG. 1 illustrates a schematic infection detection system in accordance with aspects of the invention.

[0022] FIGS. 2-5 illustrate views of an infection detection system in accordance with aspects of the invention including a two-part sampling device with meter.

[0023] FIGS. 6-8 illustrate views of an infection detection system in accordance with aspects of the invention including a detachable mini-meter.

[0024] Features of the infection detection system according to aspects of the invention are described with reference to the drawings, in which like reference numerals refer to like parts throughout.

Detailed Description

[0025] FIG. 1 shows an schematic representation of an exemplary infection detection system 10 in accordance with aspects of the invention. The infection detection system 10 is configured to process a sample and to determine whether the sample contains one or more predetermined pathogens. The infection detection system 10 in accordance with embodiments of the invention includes a sampling device 20, a lysing chamber 30, a filter 40, a meter 50, a nucleic acid sequence-based (NASBA) fluidic network 60, and an instrument 70. The infection detection system 10 also includes a sample processor 80, such as a cartridge, which at least includes the NASBA fluidic network 60 and may include any or all of the lysing chamber 30, the filter 40, and the meter 50. The sample processor 80 is configured to connect to the sampling device 20 and to receive and process a sample contained within the sampling device 20. The sample processor 80 may be disposable and replaceable, and may be adapted to process the collected sample using at least one NASBA assay. The infection detection system 10 may process the sample and determine whether the sample contains one or more predetermined pathogens rapidly, for example within an hour, thirty minutes, or less. The infection detection system 10 may process the sample and determine whether the sample contains one more predetermined pathogens at the point-of- care, for example within the same building, room, etc. as the patient. The infection detection system 10 thus eliminates the need for time-wasting intermediary treatment, storage, and/or extraneous transport of the sampling device 20. According to aspects of the invention, the entirety of the sample processing may occur within the various components of the infection detection system 10 thereby obviating the need of direct user intervention with the sample after the sample is collected. The infection detection system 10 may accordingly be used by a user of low skill and may be readily transported to and applied in a variety of environments (e.g., the home, a hospital room, etc.). As a result, infection in a patient may be rapidly detected and identified, which may improve the prognosis of the patient.

[0026] In accordance with a variety of embodiments of the present disclosure, pathogenic microorganisms and/or sequences related to antibiotic resistance are detected in a biological sample obtained from a patient. For the purposes of this disclosure, a biological sample includes whole blood, serum, plasma, cerebrospinal fluid (CSF), urine, synovial fluid, breast milk, sweat, tears, saliva, semen, feces, vaginal fluid or tissue, sputum, nasopharyngeal aspirate or swab, lacrimal fluid, mucous, or epithelial swab (buccal swab), and tissues (e.g., tissue homogenates), organs, bones, teeth, among others). For the purposes of this disclosure, a pathogenic microorganism includes, for example, one or more of Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus epidermidis, Candida parapsilosis, Streptococcus pneumoniae, Enterobacter cloacae complex, Haemophilus influenzae, Neisseria meningitidis, and Enterobacter aerogenes. For the purposes of this disclosure, an antibiotic resistance includes, for example, resistance to one or more of Fluconazole, Methicillin, Carbapenem, and Vancomycin. More particularly, the pathogenic organisms and/or antibiotic resistance markers may include those listed in Table I. More particularly still, the target sequences of the pathogenic organisms and/or antibiotic resistance genes may be detected using the various forward primers, reverse primers, and molecular beacons listed in Table I (which sets forth and defines SEQ. ID. Numbers 1 through 96). Table I

[0027] The forward primers, reverse primers, and molecular beacons listed in Table I are particularly suitable for use in the infection detection system 10. In this regard, these forward primers, reverse pnmers, and molecular beacons are optimized for use with a NASBA amplification and detection system. For example, the primer and beacons described below in reference to the NASBA fluidic network 60 may include any of the primers and beacons listed in Table 1. [0028] A lysing solution suitable for use in the infection detection system 10 quickly lyses microbial cell wall and membranes. In a particular example, the lysing solution may facilitate this lysis at room temperature and without physio-mechanical cell disruption.

In addition, the lysing solution may be benign to RNA and stable at room temperature. A specific example of a suitable lysing solution is found in Table II:

Table

[0029] It is an advantage of the lysing solution according to Table II that it is suitable for use in lysing a variety of gram positive, gram negative, and fungal microorganisms. In addition, it is an advantage of the lysing solution according to Table I that it has a viable shelf life of greater than 1 year of storage at room temperature. In addition, it is an advantage of the lysing solution according to Table I that it has a viable shelf life of greater than 1 year of storage at negative twenty degrees Celsius (-20°C). Of note, IGEPAL CA-630 ^® is a nonionic, non-denaturing detergent having the IUPAC name of octylphenoxypolyethoxyethanol. The lysing agent described below may correspond to any of the lysing solutions listed in Table II.

[0030] The sampling device 20 of the infection detection system 10 may be adapted to collect a sample, such as blood (e.g., whole blood), urine, fecal matter, purulence/pus, etc. Whole blood, as used herein, means blood drawn directly from a patient from which none of the components, such as plasma, platelets, or pathogens, has been removed. The sampling device 20 may collect the sample from a medical device (not shown). For example, the sampling device 20 may be exposed for a predetermined and/or extended period of time to an internal space or lumen in the medical device so as to collect a sample of any pathogen which may form in said space and/or lumen. The medical device may be an external communicating device used for treating a patient, such as a Foley catheter, a vascular catheter, a suction catheter, a bronchial scope, a urinary drain line, a respiratory suction catheter, a Bronco- Alveolar-Lavage Catheter, etc. The sampling device 20 may additionally or alternatively be adapted to collect a sample directly from a sample source such as urine, fecal matter, purulence/pus, a suspected infection site (such as a surgical dressing, wound, and/or an insertion site), etc. The sampling device 20 may additionally or alternatively be adapted to collect a sample intravenously, subcutaneously, or intraosseously. The sampling device 20 may be disposable and replaceable. According to aspects of the invention, the sampling device 20 may include a sample collection tube. The sample collection tube may be a standard blood collection vacuum tube containing a whole blood sample. Additionally or alternatively, the sampling device 20 may be a standard syringe containing a whole blood sample.

[0031] The lysing chamber 30 may be any chamber configured to receive the whole blood sample and lyse the whole blood sample into a lysate. The lysing chamber 30 may be in fluid communication with the sampling device 20. Fluid communication, as used herein, may mean that the structures in question are fluidly connected via any of a number of structures such as tubing, conduits, etc., that allow fluid to travel from one structure to another. In embodiments of the invention, flow of the whole blood sample from the sampling device 20 to the lysing chamber 30 may be operatively connected to the instrument 70 and may be controlled and/or driven by the instrument 70. Throughout this disclosure, reference is made to the instrument 70 controlling and/or driving fluid flow, for example flow of the whole blood sample from the sampling device 20 to the lysing chamber 30. The instrument 70 may control and/or drive fluid flow when operatively connected to a fluid pathway and via any number of known fluid control systems, which may for example include pumps, valves, conduits etc. Further, the instrument 70 may control and/or drive fluid flow without physically contacting the fluid. Accordingly, the sample collector and/or the sample processor 80 maybe disposed and replaced while the instrument 70 may be used repeatedly without contaminating the samples.

[0032] The lysing chamber 30 may include all of the materials for lysing the whole blood sample and pathogen cells contained therein and for extracting and purifying pathogen messenger RNA (i.e., dissolve targeted mRNA and remove inhibitors that could interfere with nucleic acid amplification). For example, the lysing chamber 30 may include a lysing agent, such as a lyophihzed Acris lysing chemistry, that is configured to lyse the whole blood sample into the lysate. Additionally or alternatively, the lysing chamber 30 may physically lyse the whole blood sample ultrasonically or by freezing the whole blood sample. [0033] According to one aspect of the invention shown in FIG. 1, the lysing chamber 30 may include a plurality of chambers, for example, a first chamber and a second chamber, The first chamber may include a lysing chemistry, such as, the lyophilized Acris lysing chemistry. The lysing chemistry contained within the first chamber may be in the form of a reagent plug(s) having dried lysis reagents. The first chamber may be in fluid communication with the sampling device 20 and may receive the whole blood sample from the sampling device 20. In embodiments of the invention, the instrument 70 may control and/or drive flow of the whole blood sample from the sampling device 20 to the first chamber. Additionally or alternatively, the whole blood sample may be driven from the sampling device 20 to the first chamber via gravity, capillary flow, etc. The second chamber may include a diluent and may be in fluid communication with the first chamber. The diluent may be driven from the second chamber to the first chamber to form the lysate. The instrument 70 may control and/or drive the flow of the diluent from the second chamber to the first chamber. The lysate formed in the first chamber may contain the lysing agent, the diluent, and the whole blood sample. The diluent may be driven to the first chamber in advance of the arrival of the whole blood sample to prepare the lysate. Alternatively, the diluent and the whole blood sample may be driven to the first chamber simultaneously.

[0034] The filter 40 is in fluid communication with the lysing chamber 30 and is configured to filter 40 the lysate into a filtered lysate. The filter 40 may filter out large, opaque structures from the lysate (e.g., hemoglobin) while allowing any genetic material from pathogen targets within the lysate to pass through the filter 40 for subsequent processing and analysis. In embodiments of the invention, the instrument 70 may control and/or drive the flow of the lysate from the lysing chamber 30 and to through the filter 40 to form the filtered lysate. While FIG. 1 discloses a filter 40 downstream from the lysing chamber 30, a filter 40 may additionally or alternatively be provided upstream of the lysing chamber 30.

Accordingly, in embodiments of the invention a filter 40 may be provided to filter the whole blood sample from the sampling device 20.

[0035] The meter 50 is in fluid communication with the filter 40 and is configured to meter a predetermined amount of filtered lysate for the NASBA analysis. The predetermined amount may, for example, be between 1 and 3 ml. In embodiments of the invention, the instrument 70 may control and/or drive the flow of the filtered lysate from the filter 40 and to the meter 50 to collect the predetermined amount of filtered lysate. While FIG. 1 discloses the meter 50 downstream from the lysing chamber 30 and the filter 40, in embodiments of the invention an additional or alternative meter 50 may be provided upstream of the lysing chamber 30 and/or of the filter 40. Accordingly, in embodiments of the invention a meter 50 may be provided to meter the whole blood sample and/or a filtered whole blood sample from the sampling device 20.

[0036] The NASBA fluidic network 60 may be in fluid communication with the meter 50 and may receive the predetermined amount of filtered lysate from the meter 50. The NASBA fluidic network 60 may include all of the materials (e.g., reagents, structures, etc.) necessary to perform predetermined NASBA-based nucleic-acid assay s for mRNA and/or DNA on the predetermined amount of filtered lysate. The NASBA fluidic network 60 may include a plurality of reaction tubes that are each directly or indirectly in fluidic communication with the meter 50 and that are configured to receive filtered lysate from the meter 50. In embodiments of the invention, the instrument 70 may control and/or drive flow of the filtered lysate from the meter 50 to each of the plurality of reaction tubes.

[0037] Each of the plurality of reaction tubes may include all of the materials for processing the filtered lysate for isothermal amplification of predetermined genetic sequences of pathogen target (e.g., targeted mRNA to identify the presence of specific genes). Specific examples of materials that may be included in each of the plurality of reaction tubes include lysing buffers, mRNA-dependent DNA polymerase, mRNA primers, DNA primers, amino acids, and the like. Each of the plurality of reaction tubes may at least include an enzyme, a primer, and a beacon for performing an NASBA assay on a pathogen target within the filtered lysate. Each of the plurality of reaction tubes may include one or more of the following three enzymes: Avian Myeloblastosis Virus (AMV) Reverse Transcriptase, a Ribonuclease H (RNase H), and a T7 RNA polymerase. Each of the plurality of reaction tubes may include two or more oligonucleotide primers. The enzyme(s) and the primer(s) may amplify a predetermined genetic sequence in the pathogen target. The beacon provided in each of the plurality of reaction tubes may be configured to attach to the predetermined genetic sequence in the pathogen target. The beacon may include a fluorophore that emits light when attached to the predetermined genetic sequence of the pathogen target and when excited by an excitation source (e.g., a laser). Each reaction tube may include at least one window such that the instrument 70 may detect light emitted from the beacon when attached to a pathogen target. Each reaction tube may be provided with a beacon that is different from the beacons provided in each of the other reaction tubes. Accordingly, the NASBA fluidic network 60 may detect as many different predetermined pathogen targets as there are reaction tubes.

[0038] The NASBA fluidic network 60 may include a chamber containing an NASBA diluent. The chamber may be in fluid communication with each of the plurality of reaction tubes. In embodiments of the invention, the instalment 70 may control and/or drive flow of the diluent from the chamber to each of the plurality of reaction tubes. The diluent contained within the chamber may be fluidly communicated to each of the plurality of reaction tubes a predetermined period (e.g., 5 minutes) before introduction of the filtered lysate. After expiration of the predetermined period, the filtered lysate may be distributed to each of the plurality of reaction tubes to induce the NASBA reactions and the results of the NASBA reactions may be analyzed by the instrument 70.

[0039] The instrument 70 of the infection detection system 10 may be adapted to receive the sample processor 80, to initiate and/or control aspects of processing of the sample within the sample processor 80, and to analyze the processed sample. As discussed in detail above, the instrument 70 may control and/or drive fluid flow (e.g., whole blood flow, diluent flow, lysate flow, filtered lysate flow, etc.). In addition, the instrument 70 may include a heater and/or a heat exchanger that may maintain the sample processor 80 within a predetermined temperature range necessary for isothermal amplification of predetermined pathogen targets during the NASBA assays. The predetermined temperature range may be within 35-50 degrees Celsius. In embodiments, the predetermined temperature range my be within 40 - 42 degrees Celsius.

[0040] In embodiments of the invention, the instrument 70 may be configured to perform any suitable NASBA-based nucleic-acid assay on the sample utilizing the reagents. For example, the instrument 70 may be configured to perform any steps for lysing pathogen cells and extracting and purifying pathogen messenger RNA (i.e., dissolve targeted mRNA and remove inhibitors that could interfere with nucleic acid amplification). In another example, the instrument 70 may be configured to perform any steps for processing the output solution from the extraction and purification steps for isothermal amplification of targeted mRNA to identify the presence of specific genes.

[0041] In embodiments of the invention, the infection detection system 10 includes a sampling device 20 configured to collect a whole blood sample containing a pathogen target. The infection detection system 10 includes a meter 50 configured to be removably connected to a portion of the sampling device 20 to meter a predetermined amount of the whole blood sample, and a sample processor 80 comprising a NASBA fluidic network 60 configured to be in fluid communication with the meter 50 to receive the whole blood sample. The NASBA fluidic network 60 includes an enzyme and a primer for amplifying a predetermined genetic sequence in the pathogen target, and a beacon that is configured to attach to the predetermined genetic sequence in the pathogen target. The infection detection system 10 includes an analytical instrument 70 configured to identify the beacon when the beacon is attached to the predetermined genetic sequence in the pathogen target to signal a presence of the pathogen target.

[0042] The infection detection system 10 may further include a filter 40 configured to filter the whole blood sample, and/or a lysing chamber 30 configured to lyse the whole blood sample into a lysate.

[0043] As shown in FIGS. 2-5, the sampling device 20 of the infection detection system 10 may include a first tube 202 and second tube 204. The first tube 202 may include the portion of the sampling device 20 and the second tube 204 may include the meter 50. The first tube 202 and the second tube 204 are removably coupled via luer fittings 212. The sampling device 20 further comprises a duckbill umbrella valve 206 and a piston 208 disposed within the second tube 204. According to this embodiment, the sample collector collects, filters, meters, and is then removed to be transferred directly to and locked into the cartridge (i.e., the sample processor 80). A key benefit is deriving a sample while simultaneously filtering and measuring the sample. This embodiment mimics the size of a standard vacuum blood collection to interface with standardized needle set accessories and accommodate the current workflow for clinicians.

[0044] The two part blood collection tube 200 allows for a vacuum mechanism to draw the sample to enter the collection chamber 210 where a filter 40 may reside. At the base of the first chamber is a connection and an umbrella valve 206 mechanism allowing the filtered sample to pass through into the second chamber - where the final metered amount will reside. The first chamber allows for capture of overflow of sample once the metered chamber is filled. The two chambers in the collection two unlock into two separate pieces allowing for easy transfer of the metered volume to the cartridge. The umbrella valve 206 aspect of the duckbill-umbrella valve 206 is engaged once the secondary chamber (metered volume) is attached to the microfluidics cartridge, allowing the filtered, metered sample to flow through the microfluidics cartridge. When this chamber is attached to the cartridge it locks, closing the system preventing contaminates from entering and biohazards from existing the cartridge. FIG. 5 shows and describes a storyboard of an intended use of this embodiment of the invention. The component(s) shown in FIGS. 2-5 and described above are intended to be used in an infection detection system 10, such as the infection detection system 10 shown schematically in FIG. 1 and described in detail above. Accordingly, the present invention includes an infection detection system 10 shown in FIG. 1 and described in detail above having any of the component(s) shown in FIGS. 2-5 and described above. [0045] FIGS. 6-8 show aspects of an infection detection system 10 including mini meter 600. The mini meter 600 structure includes a housing enclosing an internal metering and/or filtering mechanism 706 and a removable metered sample well 700 disposed within the housing. The housing is configured to connect to the portion of the sampling device 20 to draw the whole blood sample from the sampling device 20. The metered sample well 700 being configured to meter the predetermined amount of the whole blood sample. The metered sample well 700 is configured to be removed from the housing and connected to the sample processor 80 and to fluidly communicate the predetermined amount of the whole blood sample to the sample processor 80. Further, this sample acquisition embodiment may utilize a standard vacuum blood collection tube which interfaces with the device that filters the sample while metering it at in close proximity to the patient (e.g., bedside) with little oversight from the clinician. The sample after being filtered and metered is transferred into a small collection tube (the metered sample well 700) which is directly inserted into the microfluidics cartridge and locked in and cannot be removed. This helps to prevent contaminants from getting into the sample and biohazards from escaping the cartridge once the sample is inserted.

[0046] The filtration and separation prior to entering the cartridge optimizes the sample for optical analysis. The blood collection tube vacuum is used to draw the sample, so the smaller metered collection tube is pressurized while the device itself has a two valve system allowing for pressure displacement and the sample to be drawn into the smaller metered collection tube. This device filters and meters with minimal input or steps from the clinician, reducing the workload and complexity for the clinicians. The simple nature of this would allow for diagnostics to be performed at bedside as it removes the manual dilution and centrifuging steps typically associated with rapid diagnostics. The component(s) shown in FIGS. 6-8 and described above are intended to be used in an infection detection system 10, such as the infection detection system 10 shown schematically in FIG. 1 and described in detail above. Accordingly, the present invention includes an infection detection system 10 shown in FIG. 1 and described in detail above having any of the component(s) shown in FIGS. 6-8 and described above.

[0047] An embodiment of the invention includes a method of detecting an infection using any of the above-described infection detection systems. The method includes collecting the whole blood sample containing the pathogen target, metering the predetermined amount of the whole blood sample in the meter, removing the meter and connecting the meter to the sample processor 80, amplifying the predetermined genetic sequence in the pathogen target, attaching the beacon to the predetermined genetic sequence of the pathogen target, and exciting the beacon attached to the pathogen target to signal the presence of the pathogen target.

[0048] The many features and advantages of the infection detection system 10 and methods described herein are apparent from the detailed specification, and thus, the claims cover all such features and advantages within the scope of this application. Further, numerous modifications and variations are possible. As such, it is not desired to limit the infection detection system 10 to the exact construction and operation described and illustrated and, accordingly, all suitable modifications and equivalents may fall within the scope of the claims.