Blood testing represents a significant majority of human medical testing needs. Coupled with the growing need for physicians to monitor efficacy of drug therapy, there is also a growing need and demand for a portable quantitative point of care (POC) testing system. POC testing is projected to reach 22 billion dollars sometime in 2022. Typically, a large majority of blood tests are done in a central laboratory with expensive and complicated robotics. In order for many blood tests to reach the POC market the tests will, at a minimum, have to be simple to do and provide the same precision and accuracy as generated by the central laboratories. Moderately complex (for example, ELISA) technology has allowed physicians to avoid the central laboratory in some cases. However, these technologies are not generally available to Clinical Laboratory Improvement Amendments (CLIA) licensed POC physicians and are typically not subject to the Food and Drug Administration (FDA) CLIA waved status and therefore not available for point of care testing. Previous efforts to provide quantitative point of care testing have relied on pre-made calibration curves set at the date of manufacture and transmitted via barcode or chip device sold with the disposable test. However, pre-made calibration curves have significant limitations.
The disclosed techniques can overcome issues with previously used techniques as a sample with an analyte of interest is run concurrently with a calibration strip that includes different concentrations of the analyte of interest being measured in the sample strip or a control analyte (i.e., an analyte that is distinct from the analyte of interest), while also utilizing the same binding agents. Any minor instability of the detector binding agent is thus applicable to the same degree on the construct of the calibration curve and the patient sample. In other words, the disclosed system is self-correcting and capable of producing repeatable and accurate results.
Various devices and methods of quantitative and qualitative analysis are described herein. Specifically, a cassette is disclosed that includes an ‘on-board’ calibrator. The cassette includes, in many cases, a lateral flow strip for calibration and a lateral flow strip for a sample. The lateral flow strips are formed of porous membranes which permit capillary motion of fluid. The “calibration strip” includes at least two and, in some cases, three, four, or more regions with known concentrations of an analyte (either the analyte of interest in the sample or a control analyte). To use the cassette for analysis, a sample is deposited on the “sample strip” and a chase fluid is supplied to both the sample strip and the calibration strip. The chase fluid releases a conjugate substance from pads in contact with the sample strip and the calibration strip and the conjugate substance then travels up the strips. The conjugate substance is a binding partner to the analyte of interest and may comprise or consist of a marker. On the calibration strip, the conjugate substance encounters and binds with the analyte present. Once bound to the analyte (either directly or indirectly via a distinct binding partner), the marker emits a signal, which is directly proportional to the amount of analyte present. The signals that develop on the calibration strip are then interpreted optically by an instrument to generate a calibration curve which is used to calculate or interpret the concurrent signal that develops on the sample strip. The disclosed cassettes may be compatible with an instrument capable of interpreting images either through light transmission or light reflectance. In embodiments where increased sensitivity is desired, light transmission can be used.
The disclosed cassettes can be configured to measure any desired analyte of interest. For example, the cassettes can be configured to measure antigens, antibodies, hormones, proteins, receptors, DNA, RNA, enzymes, pharmaceutical substances, and/or environmental pollutants. Appropriate binding partners and/or markers can be selected based on the selected analyte of interest and/or control analyte and used to create an appropriate calibration strip and sample strip.
In one particular example embodiment, a cassette is designed to measure an antigen of interest. The calibration strip for this cassette includes known concentrations of the antigen and an antibody immunologically bound to the antigen. In this example embodiment, the cassette includes a conjugate pad with marker (for example, gold particles). When chase fluid is introduced, the marker is reconstituted and travels to and bind with the antigen bound to the antibody. On the sample strip, the sample mixes and together with the chase fluid reconstitutes the marker (in this example, colloidal gold detector particles) and moves onto a porous membrane. If antigen is present, a signal develops.
In a different example embodiment, a cassette is designed to measure an antigen of interest and the calibration strip includes known concentrations of an antigen bound to a marker. In this example embodiment, the conjugate pad includes antibodies which travel to and bind with the antigen bound to the marker when chase fluid is introduced. The cassettes disclosed herein may include a calibration strip and a sample strip with numerous possible combinations of suitable binding partners and/or markers for particular analytes of interest. Although antibodies and antigens are discussed in detail, the subject disclosure is not intended to be so limited. For example, sample and calibration strips that include analytes such as hormones, proteins, vitamins, enzymes, DNA, RNA, pharmaceutical substances, and/or environmental pollutants are all within the scope of the subject disclosure.
Surprisingly, the disclosed cassettes with “on-board” calibration features are able to distribute fluid, sample, binding agents and/or markers up two lateral flow strips evenly and with inconsequential variation. Furthermore, the disclosed cassettes are able to produce a robust and stable calibration curve from the calibration strip and accurately report an unknown quantitative result from the sample strip.
Testing devices, namely cassettes, are disclosed that provide “on-board” calibration functionality. In particular, the disclosed cassettes include a calibration strip and a sample strip, each formed of a porous material that permits fluid to flow therethrough using capillary force. The calibration strip contains known quantities of analyte, from which a calibration curve can be created and applied to the analysis of the sample strip. The cassette may include a separate wash port for rapid washing of a high background sample.
The cassette produces a signal, which can be read using light transmission or light reflectance techniques. The disclosed cassettes can be used in diagnostic tests for humans, animals, environmental sample, and/or food samples. If desired, the disclosed devices and techniques may be used to monitor efficacy of drug therapy and/or patient compliance with respect to physician-prescribed medication in a point of care (POC) setting. Details regarding construction of the cassette, calibration strip, and sample strip are described below in detail, along with related methods of use.
Cassette
The bottom portion 8 of the cassette housing may also include side walls 15, which surround strips 2 and 7 (shown in
In some embodiments, top portion 1 includes a plurality of pressure points 18, with an equal number of pressure points 18 in contact with sample strip 2 and calibration strip 7.
Calibration Strip
The capillary flow substrate 104 of calibration strip 7 may include marker regions 106 that include known concentrations of an analyte, a binding partner for the analyte, and/or a marker which, when bound to the analyte or to a binding partner bound to the analyte, emits a detectable signal. In some embodiments, the analyte on the calibration strip 7 is the same as the analyte of interest in the sample, while in other embodiments, the analyte on the calibration strip 7 is a control analyte that is distinct from the analyte of interest in the sample. In embodiments where a control analyte is used, the control analyte may be an analyte that binds to the same binding agents as the analyte of interest. The marker regions 106 may include appropriate components based on the design on the assay employed for the testing device. For example, if an example assay is designed to detect an antigen (as the analyte of interest), the assay may use an antibody as the binding partner and a gold particle as the marker. In some such embodiments, the marker regions 106 may include known quantities of antigen bound to antibody or known quantities of antigen and gold particles. In embodiments where the marker regions 106 include antigen bound to antibody, the gold particles may be included in a conjugate pad 110 and travel upwards to the marker regions 106 during the assay. Once the gold particles encounter the antigen bound to antibody, they may bond to form a complex. In embodiments where the marker regions 106 include antigen and gold particles, the conjugate pad 110 may include antibodies which travel upwards to the marker regions 106 during the assay and form a complex with the antigen and gold particles.
Numerous configurations and variations of the assay employed by the disclosed testing device are possible. For example, in some embodiments, the analyte of interest may be a receptor, hormone, antigen, antibody, protein, enzyme, DNA, RNA, vitamin, pharmaceutical substance, and/or environmental pollutant. In such cases, a suitable binding partner can be selected based on the identity of the analyte of interest. For example, suitable binding partners may be organic compounds, inorganic compounds, receptors, antigens, antibodies, hormones, enzymes, proteins, and/or DNA. Example markers beyond colloidal gold that may be used to bind to the analyte of interest directly or indirectly include but are not limited to: enzymes (such as horseradish peroxidase, alkaline phosphatase, or glucose oxidase), selenium, radioactive isotopes, DNA reporters, fluorogenic reporters (such as phycoerythrin), and/or electro chemiluminescent tags, inorganic compounds, such as silicon dioxide, ferric oxides, and chemical derivatives of inorganic compounds.
Additionally, the assay of the disclosed testing device may be competitive or non-competitive and may include one, two, or more binding sites. For example, the assay may be a one-site non-competitive assay in which the analyte binds with a marked binding partner (for example, a labelled antibody) and signal from the marked binding partners is measured to determine the concentration of analyte. In other embodiments, the assay may be a two-site non-competitive assay in which analyte binds to both a first binding partner (for example, an antibody site) and a marked binding partner (for example, a labelled antibody). This type of assay is commonly known as a “sandwich assay.” In other embodiments, the assay may be a competitive assay, in which unmarked analyte competes with marked analyte to bind to a binding partner (for example, an antibody). The amount of marked, unbound analyte is then measured and used to calculate the concentration of (originally unmarked) analyte in the sample.
The example calibration strip 7 shown in
As shown in
In some embodiments, a sample pad 112 may be positioned on the calibration strip 7 at least partially overlapping conjugate pad 110. Sample pad 112 may be implemented with any appropriate material, such as nitrocellulose or another porous material. As described below in detail, sample strip 2 includes a sample pad onto which sample is deposited. In embodiments where sample strip includes a distinct sample pad, calibration strip 7 may also include a similarly-sized sample pad 112, as shown in
Additionally, calibration strip 7 may also include an absorbent pad 108, as shown in
As will be understood by those skilled in the art upon consideration of the subject disclosure, calibration strip 7 may include fewer or more distinct portions than those shown in
Sample Strip
As shown in
Working Example 1
In a first example embodiment, a cassette includes a sample strip and a calibration strip designed to quantitatively test for Respiratory Syncytial Virus (RSV). The common lateral flow architecture for the sample strip and the calibration strip is as follows.
An example lateral flow strip was constructed using Lohmann Corporation adhesive backing plastic (0.010″ White or clear polyester laminated with GL-187® acrylic PSA & supported with a release liner). Sartorius 25 mm CN140 Nitrocellulose was placed on top of the Lohmann backing material approximately 37 mm from the bottom of the backing material. 22 mm wide absorbent pad material CF5 from Whatman/GE was indexed with the top of the Lohmann backing material, creating an overlap onto the nitrocellulose and corresponding with pressure points of the cassette housing. On the lower side of the nitrocellulose a conjugate pad material is placed (14 mm Ahlstrom 6614, and/or Ahlstrom 1281 placed so that it creates an overlap on top of the nitrocellulose). A final 24 mm sample application material is indexed to the bottom of the Lohmann backing material to create an overlap onto the conjugate pad material. Once all components were assembled, the laminated material was then cut into 6 mm wide strips using a Biodot guillotine cutter. Additionally, a 10×15 mm fluid pad made from Ahlstrom 6614 was cut and placed over the bottom of the strips. To immunologically bind antigen, nitrocellulose is used to bind antibodies directed against the antigen of interest in the range of 50 pg/ml-3 mg/ml. A Biodot dispensing platform was used to accurately dispense four lines of antibody. The nitrocellulose was subsequently dried under forced hot air. With a second pass through the Biodot dispensing platform, antigen was dispensed on top of the antibody and subsequently dried. To create the increasing signal intensity ladder, increasing amounts of antigen (ng/mL) was used per line (lowest at the bottom). Detector antibody bound to gold particles from the same lot and concentration as the sample strip is applied to the conjugate pad material and dried.
The sample strip was constructed by depositing monoclonal anti RSV from Virostat Inc at 1.5 mg/mL onto Sartorius CN140 nitrocellulose using a Biodot dispensing system at a rate of 1 uL/cm. A goat anti chicken control line at 0.5 mg/mL was also deposited north of the RSV line at a rate of 1 uL/cm. Ahlstrom 1281 overlapped onto the nitrocellulose and Ahlstrom 6614 served as the sample/conjugate pad. A solution containing anti RSV from Virostat Inc conjugated to BBI 60 nm colloidal gold particles, and chicken IgY conjugated to BBI 40 nm colloidal gold particles were sprayed down onto the Ahlstrom 6614 using the Biodot dispensing system at a rate of 15 uL/cm and dried. Once laminated onto the Lohmann backing material, these strips were cut to 6 mm wide using the biodot cutter.
The calibration strip of this example embodiment was constructed as follows. Monoclonal anti RSV from Virostat Inc at 1.5 mg/mL was deposited into four evenly spaced lines onto Sartorius CN140 nitrocellulose using the Biodot dispensing platform and dried. With a second pass on the biodot dispensing platform, dilutions of RSV antigen positive control from Zeptometrix (40% on line 1, 60% on line 2, 80% on line 3 and 100% on line four) were deposited on top of the antibody lines and dried.
A chase fluid for the RSV reagents was prepared using Triton ×100, Tris buffer and Proclin 300. This solution was added to the fluid entry port after the sample was added.
The described calibration and sample strips were assembled into a cassette along with a fluid pad. 20 uL of patient sample prepared from a nasal swab, nasal pharyngeal swab, nasal wash or viral transport media was added to the sample entry port. 300 uL of chase fluid was added to the fluid entry port. The cassette was then allowed to react at room temperature for 10 min. Signals from the four calibration lines on the calibration strip were recorded using a light reflectance lateral flow reader system from Detekt Biomedical and compared against unknown signals generated from the sample strip. Each cassette received its own calibration calculated from signals generated at the 10 min time point. Data obtained from this example was then compared to standards (dilutions of a positive control) to determine the accuracy of the cassette devices. Table 1 shows the results obtained.
As shown in Table 1, the example testing device accurately predicted the percentage dilution of the positive control solution. Additionally, the largest difference recorded was less than a 7% error in measurement. In some embodiments, the quantitative measurement of the analyte concentration in the sample has an error percentage of less than 5%, 4%, 3%, 2%, or 1%.
Working Example 2
In another example embodiment, a kinetic lateral flow test was created to detect human thyroid stimulating hormone (TSH) levels in whole blood. The example testing device was constructed according to the following procedure. The calibration strip and sample strip were produced according to the common lateral flow architecture described in working example 1.
The sample strip was created by depositing monoclonal anti TSH (Biospacific) at 2 mg/mL onto 28 mm Sartorius CN140 nitrocellulose using a Biodot dispensing system at a rate of 1 uL/cm. A goat anti chicken control line at 0.5 mg/mL was also deposited north of the TSH line at a rate of 1 uL/cm. Ahlstrom 6614 (14 mm) overlapped the nitrocellulose and served as the conjugate pad material. A solution containing monoclonal anti TSH (Biospacific) conjugated to BBI 60 nm colloidal gold particles and chicken IgY conjugated to BBI 40 nm colloidal gold particles were sprayed down onto the Ahlstrom 6614 using the Biodot dispensing system at a rate of 15 uL/cm and dried. Once laminated onto the Lohmann backing material, these strips were cut to 6 mm wide using the Biodot cutter.
The calibration strip was constructed by depositing four evenly spaced lines of the same antibody and concentration used for the sample strip onto Sartorius CN140 nitrocellulose using the Biodot dispensing platform and dried. With a second pass on the biodot dispensing platform, TSH from Scripps Laboratories diluted into TSH free human serum (3.6 ng on line 1, 0.36 ng on line 2, 0.036 ng on line 3 and 0.0036 ng on line four) was deposited on top of the antibody lines and dried.
A chase fluid was developed to be compatible with the TSH reagents and to limit blood hemolysis. The chase fluid solution incorporated Tween 20, Sodium bicarbonate, and EDTA. This solution was added to the fluid entry port after the sample was introduced.
The example calibration and sample strips were assembled into the cassette along with a fluid pad. 20 uL of patient sample was added to the sample entry port and 200 uL of assay run fluid was added to the fluid entry port.
The cassette was then inserted into a light transmission instrument (OIDx) which was capable of kinetically analyzing the cassette over time. Signals from the four calibration lines were recorded and compared against unknown signals generated from the sample. Each cassette received its own calibration calculated from signals generated at various time points. To determine the accuracy of the on-board calibration system, known standards were run as samples (Dilutions of World Health TSH standard).
As shown in
Working Example 3
In another example embodiment, a cassette was designed to detect human TSH levels in whole blood, which can cause background staining when used as a sample. The light transmission and sample volume analysis were also assessed. The calibration strip and sample strip were produced according to the common lateral flow architecture described in working example 1. The example cassette was constructed as follows.
The sample strip was prepared by depositing monoclonal anti TSH(Biospacific) at 2 mg/mL onto 28 mm Sartorius CN140 nitrocellulose using a Biodot dispensing system at a rate of 1 uL/cm. A goat anti chicken control line at 0.5 mg/mL was also deposited north of the TSH line at a rate of 1 uL/cm. Ahlstrom 6614 (14 mm) overlapped the nitrocellulose and served as the conjugate pad material. A solution containing monoclonal anti TSH(Biospacific) conjugated to BBI 60 nm colloidal gold particles and chicken IgY conjugated to BBI 40 nm colloidal gold particles were sprayed down onto the Ahlstrom 6614 using the Biodot dispensing system at a rate of 15 uL/cm and dried. Once laminated onto the Lohmann backing material, these strips were cut to 6 mm wide using the Biodot cutter.
Chase fluid was developed to be compatible with the TSH reagents and to limit blood hemolysis. The chase fluid solution incorporated Tween 20, Sodium bicarbonate, and EDTA. This solution was added to the fluid entry port after the sample was introduced. 25 uL of a highly hemolyzed whole blood sample was added to the sample port and then tested as normal. At nine minutes into the assay, the cassette was visually evaluated for problems due to hemolysis. Table 2 describes what was observed and how the wash port was used to clear up the background.
As shown in this example embodiment, the wash port can provide an effective way of clearing high background samples. Furthermore, the wash port is also amenable to automated practices. For example, in some embodiments, a cassette may be configured to automatically apply a solution via the wash port when background noise of a certain signal intensity is detected. Numerous implementation techniques will be apparent to one skilled in the art upon consideration of the subject disclosure.
Working Example 4
In another example embodiment, an instrument was created to measure light transmission and sample volume. This example instrument is referred to as “OIDx” herein. The OIDx instrument was programmed to measure pixel area from an image. To program the instrument, various amounts of whole blood were added to the sample port of an example cassette. An image of the strip was captured 30 seconds after the whole blood was added.
As can be seen in
Working Example 5
In another example embodiment, a cassette was created to detect histoplasma in urine. The sample strip for the cassette was constructed using the common lateral flow architecture as previously described. To create the sample strip, rabbit monoclonal anti Histoplasma Capsulatum at 1.5 mg/mL was deposited onto 25 mm Sartorius CN140 nitrocellulose using a Biodot dispensing system at a rate of 1 uL/cm. A goat anti chicken control line at 0.5 mg/mL was also deposited north of the anti-Histoplasma line at a rate of 1 uL/cm. Ahlstrom 6614 overlapped the nitrocellulose and served as both the conjugate and sample pad. The Ahlstrom 6614 was treated prior to the depositing of colloidal gold to reduce interference with urine samples. A solution containing anti Histoplasma cap. conjugated to IMRA 40 nm colloidal gold particles and chicken IgY conjugated to IMRA 40 nm colloidal gold particles were sprayed down onto the Ahlstrom 6614 using the Biodot dispensing system at a rate of 15 uL/cm and dried. Once laminated onto the Lohmann backing material, these strips were cut to 6 mm wide using the Biodot cutter.
A chase fluid was developed to be compatible with the Histoplasma reagents and to limit interference from urine samples. The chase fluid solution incorporated Sodium Dodecyl Sulfate, Sodium Citrate and phosphate buffer. The described strip was placed into the cassette along with a fluid pad.
60 uL of urine spiked with known concentrations of Histoplasma capsulatum was added to the sample port. 300 uL of chase fluid was added to the fluid port and the assay was run for 10 minutes. Results were read on a Detekt Biomedical reader to quantitate signal. The data obtained is shown in
Additional Example Embodiments
The following additional example embodiments are provided to describe aspects of the presently disclosed methods and devices in further detail and are not intended to limit the scope of the subject disclosure.
In some example embodiments, a universal method for quantitative sample analysis is provided. The method may include, in some cases, a calibration curve obtained simultaneously with the sample analysis without additional user steps. In these and other embodiments, a lateral flow-based system can be achieved, where sample is added to an absorbent material which together with chase fluid reconstitutes dried colloidal gold antibody detector conjugates or other suitable detector binding agents. Through capillary force, the sample and colloidal gold detector moves laterally onto a controlled porosity membrane where binding partners such as antibodies, antigens, receptors and the like have been previously adsorbed onto the membrane. If analyte, i.e. antigen or antibody is present in the sample, a reaction occurs between the specific binding agents to produce a signal that can be read visually or quantitatively with an instrument and a calibration curve. This is commonly referred to as a ‘sandwich assay,’ where the analyte of interest is sandwiched between two suitable binding partners, one of which has a detector signal associated with the binding agent. The signal is directly proportional to the analyte concentration. In these and other embodiments, signals on the calibrator strip, which develop concurrent with the sample strip, are interpreted by an instrument to create a calibration or standard curve that the sample is compared to, thereby generating a quantitative result for the sample.
Techniques for creating a calibration curve (sometimes referred to as a ‘standard curve’) from measured signals are known to those skilled in the art. For example, measured signal may be plotted against analyte concentration and a best fit line may be generated between the data points. The best fit line may, in some cases, obey the equation y=mx+b, where y is the signal measured, m is the sensitivity (i.e., the slope of the line), x is analyte concentration, and b is a constant attributable to background. Once a best fit line is generated, unknown analyte concentrations can be determined using the equation. In some systems, the relationship between analyte concentration and signal measured may be linear or approximately linear within particular ranges of analyte concentration. The region where measured signal has a linear relationship to analyte concentration is referred to as the “linear range” herein. In some cases, the linear range may extend between the system's limit of detection (LOD) and the limit of linearity (LOL). Below the LOD, signal measured may be attributable to background interference and above the LOL, signal measured has a non-linear relationship to analyte concentration. Accordingly, measurements obtained between the LOD and the LOL (in the linear range) may produce a more reliable calibration curve than values outside the linear range.
As previously described, the disclosed devices include a calibration strip with particular analyte concentrations selected to produce signals to generate a reliable calibration curve to quantify analyte concentration in a solution that is applied to the sample strip. In some embodiments, the disclosed calibration strip includes at least one non-zero analyte concentration value. In these and other embodiments, the calibration strip may include a region with an analyte concentration of zero, from which signal is measured and then used to generate the calibration curve. In some particular example embodiments, only two signals read from the calibration strip (one from a region with a non-zero analyte concentration and another from a region with an analyte concentration of zero) may be used to generate a calibration curve. In some such example embodiments, the non-zero analyte concentration may be selected to be within the linear range to maximize accuracy. In these and other embodiments, the measured signal in a region with an analyte concentration of zero would correspond to the value of the “b” variable in the best fit line equation and would indicate signal produced from background and non-specific binding. Measuring signal from a region with an analyte concentration of zero may also be used in various embodiments to provide additional safety controls. For example, visual color developing in a region with zero analyte concentration may indicate a test failure and/or inaccuracy of results. Numerous configurations and variations will be apparent to those skilled in the art upon consideration of the subject dislcosure.
The disclosed cassettes may be compatible with an instrument capable of interpreting images either through light transmission or light reflectance. In some embodiments, a cassette may be read using light reflection and transmission-based detection methods. In embodiments where increased sensitivity is desired, light transmission can be used.
In some embodiments, the sample analysis results can be provided quantitatively. However, it is to be understood that in some embodiments, the quantitative results may be reported qualitatively, if desired. For example, in the case of TSH measurements, results may be reported as EUTHYROID, HYPERTHYROID, or HYPOTHYROID.
The disclosed methods may be used to monitor disease progression or regression with regard to medical treatment including prescriptions, in some embodiments. In some embodiments, the system may be used to monitor patient compliance with prescribed medications.
In various embodiments, the signals that develop are in addition to colloidal gold derived from nanomaterial-based Biosensors incorporating various detector strategies such as fluorescent labels, enzymes, chemiluminescence chemistries, ferromagnetic particles and silica particles.
In some cases, the quantitative result may be reported as a concentration of analyte mass per unit volume, an activity unit per unit volume or as a percentage of a reference value.
The disclosed cassettes can provide uniformity of liquid flow on both sample and calibration strips due to precision placement of pressure points within the device and suitable incorporation of barriers to ensure that migration or flow is absolutely restricted to the membrane strips. The disclosed systems can also utilize light reflection or transmission based detection with the same cassette and instrument. For certain tests such as a test for pregnancy where a number or quantitation is not required, the test can be read visually. In some embodiments, a wash port may be used to quantitate samples that feature hemolyzed whole blood or pigmented samples. The disclosed systems also may have the ability to remove interfering (false positives) particulates that may be present in certain samples by incorporating suitable membrane-based filters. The disclosed systems may also image and record the volume of sample added to the device, (for example a drop of blood from a finger prick, which would eliminate the need for accurate pipettes). Off-board mixing of colloidal gold and sample for added sensitivity and flexibility may be used in any of the disclosed assay designs.
In some embodiments, multiple sample types may be tested by the disclosed cassettes, including whole blood, urine, saliva, swabs, and/or fecal matter. With kinetic assay capability, the disclosed systems may report a result quickly (for example, within two to ten minutes), depending on sample concentration. The disclosed systems may have the ability to perform nucleic acid (PCR, rtPCR) assays and/or the ability to multiplex analytes on the same strip. The disclosed systems may also be compatible with colloidal gold, latex particles, fluorescent labels and superparamagnetic particles. In some embodiments, the calibration strip may feature a lot-specific calibrator which is referenced to a calibration curve performed at the date of manufacturing.
The features and advantages described herein are not all-inclusive and, in particular, many additional features and advantages will be apparent to one of ordinary skill in the art in view of the drawings, specification, and claims. Moreover, it should be noted that the language used in the specification has been selected principally for readability and instructional purposes, and not to limit the scope of the inventive subject matter described herein. The foregoing description of the embodiments of the disclosure has been presented for the purpose of illustration; it is not intended to be exhaustive or to limit the claims to the precise forms disclosed. Persons skilled in the relevant art can appreciate that many modifications and variations are possible in light of the above disclosure.
This application claims priority from U.S. Provisional Application Ser. No. 62/517,441, filed Jun. 9, 2017, the contents of which are incorporated by reference herein.
Number | Name | Date | Kind |
---|---|---|---|
4098876 | Piasio et al. | Jul 1978 | A |
4378344 | Zahradnik et al. | Mar 1983 | A |
4981786 | Dafforn | Jan 1991 | A |
5877028 | Chandler et al. | Mar 1999 | A |
7358099 | Piasio et al. | Apr 2008 | B2 |
8354245 | Piasio et al. | Jan 2013 | B2 |
9445749 | Erickson et al. | Sep 2016 | B2 |
9556472 | Piasio et al. | Jan 2017 | B2 |
20020173050 | DiNello | Nov 2002 | A1 |
20060008847 | Ramel | Jan 2006 | A1 |
20070020768 | Rundstrom | Jan 2007 | A1 |
20090155921 | Lu | Jun 2009 | A1 |
20090257915 | Dinello et al. | Oct 2009 | A1 |
20090258343 | Reiter | Oct 2009 | A1 |
20100035245 | Stiene et al. | Feb 2010 | A1 |
20100167264 | Lee | Jul 2010 | A1 |
20130189794 | Emeric | Jul 2013 | A1 |
20130224771 | McDade et al. | Aug 2013 | A1 |
20150064800 | Chance | Mar 2015 | A1 |
20150244852 | Erickson et al. | Aug 2015 | A1 |
Number | Date | Country |
---|---|---|
2017087831 | May 2017 | WO |
Entry |
---|
O'dell; “Fast and Convenient Vitamin Deficiency Test”; VitaScan; 2017; 3 pages. |
Hermanson; “Enzyme Modification and Conjugation”; Bioconjugate Techniques; 2013; p. 963-965; Third Edition. |
Number | Date | Country | |
---|---|---|---|
20180356393 A1 | Dec 2018 | US |
Number | Date | Country | |
---|---|---|---|
62517441 | Jun 2017 | US |