Patent Application
20220163543
Not Applicable.
The presently disclosed and claimed inventive concept(s) relate to a device(s), kit(s), and method(s) that increase the stability and/or shelf life of component(s) and/or reagent(s) utilized for the conductance of at least one diagnostic assay. More specifically, the presently disclosed and claimed inventive concept(s) relate to non-limiting embodiments of a modified reaction cassette and/or housing that comprises and/or consists of an improved antibody reaction zone for use in the conductance of at least one diagnostic assay, as well as kits and methods of use related thereto.
Numerous devices and methods exist for detecting analytes that may be present in a fluid sample. Such devices have been proven to be effective in diagnostic assays that detect the presence and quantity of certain analytes indicative of a patient's health, including, but not limited to, glycated hemoglobin (HbA1c), microalbumin and creatinine, and lipid-based analytes, such as cholesterol, triglycerides, and/or high-density lipoproteins. However, the results obtained from the conductance of such analyte detection assay(s) may be inaccurate and/or biased due to, for instance, phenotypic changes in reaction zones that comprise and/or consist of at least one diagnostic assay reagent (such as, by way of example only, an analyte-detection antibody utilized and/or contained within a reaction vessel for the conductance of at least analyte detection assay). When phenotypic changes occur to the reaction zones, for instance, due to storage of the reaction vessel over a period of time prior to use, the accuracy and efficacy of the reaction zones are decreased. These structural deficiencies in the reaction zones may result, by way of example, in the incomplete capture of an analyte of interest that is present in a patient's liquid test sample, thereby resulting in bias in the reported concentration(s) of such analyte(s) of interest. In addition, the repeated bias of individual diagnostic assays/tests resulting from the use of structurally deficient reaction zones increases the coefficient of variation (% CV) obtained from the collective dataset, thereby decreasing the accuracy and repeatability of the diagnostic assay(s).
Accordingly, there is a need for improved devices and methods that decrease, mitigate, or eliminate phenotypic variations in a reaction zone for use in at least one diagnostic assay. Such decrease, mitigation, or elimination thereby extends the shelf-life and usability period for a reaction vessel(s) that comprises the reaction zone(s) and thereby decrease inaccuracies in diagnostic assay results associated with and/or introduced by such variations. It is to such devices and methods, as well as kits related thereto, that the presently disclosed and claimed inventive concept(s) is directed.
Before explaining at least one embodiment of the inventive concept(s) in detail by way of exemplary drawings, experimentation, results, and laboratory procedures, it is to be understood that the inventive concept(s) is not limited in its application to the details of construction and the arrangement of the components set forth in the following description or illustrated in the drawings, experimentation and/or results. The inventive concept(s) is capable of other embodiments or of being practiced or carried out in various ways. As such, the language used herein is intended to be given the broadest possible scope and meaning; and the embodiments are meant to be exemplary—not exhaustive. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting.
Unless otherwise defined herein, scientific and technical terms used in connection with the presently disclosed and claimed inventive concept(s) shall have the meanings that are commonly understood by those of ordinary skill in the art. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. The foregoing techniques and procedures are generally performed according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification. The nomenclatures utilized in connection with, and the laboratory procedures and techniques of, analytical chemistry, synthetic organic chemistry, and medicinal and pharmaceutical chemistry described herein are those well-known and commonly used in the art.
All patents, published patent applications, and non-patent publications mentioned in the specification are indicative of the level of skill of those skilled in the art to which this presently disclosed and claimed inventive concept(s) pertains. All patents, published patent applications, and non-patent publications referenced in any portion of this application are herein expressly incorporated by reference in their entirety to the same extent as if each individual patent or publication was specifically and individually indicated to be incorporated by reference.
All of the devices, kits, and/or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this presently disclosed and claimed inventive concept(s) have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and/or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the presently disclosed and claimed inventive concept(s). All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the inventive concept(s) as defined by the appended claims.
As utilized in accordance with the present disclosure, the following terms, unless otherwise indicated, shall be understood to have the following meanings:
The use of the word “a” or “an” when used in conjunction with the term “comprising” in the claims and/or the specification may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.” The singular forms “a,” “an,” and “the” include plural referents unless the context clearly indicates otherwise. Thus, for example, reference to “a compound” may refer to 1 or more, 2 or more, 3 or more, 4 or more or greater numbers of compounds. The term “plurality” refers to “two or more.” The use of the term “or” in the claims is used to mean “and/or” unless explicitly indicated to refer to alternatives only or the alternatives are mutually exclusive, although the disclosure supports a definition that refers to only alternatives and “and/or.” Throughout this application, the term “about” is used to indicate that a value includes the inherent variation of error for the device, the method being employed to determine the value, or the variation that exists among the study subjects. For example but not by way of limitation, when the term “about” is utilized, the designated value may vary by ±20% or ±10%, or ±5%, or ±1%, or 0.1% from the specified value, as such variations are appropriate to perform the disclosed methods and as understood by persons having ordinary skill in the art. The use of the term “at least one” will be understood to include one as well as any quantity more than one, including but not limited to, 2, 3, 4, 5, 10, 15, 20, 30, 40, 50, 100, etc. The term “at least one” may extend up to 100 or 1000 or more, depending on the term to which it is attached; in addition, the quantities of 100/1000 are not to be considered limiting, as higher limits may also produce satisfactory results. In addition, the use of the term “at least one of X, Y and Z” will be understood to include X alone, Y alone, and Z alone, as well as any combination of X, Y and Z. The use of ordinal number terminology (i.e., “first”, “second”, “third”, “fourth”, etc.) is solely for the purpose of differentiating between two or more items and is not meant to imply any sequence or order or importance to one item over another or any order of addition, for example.
As used in this specification and claim(s), the terms “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open-ended and do not exclude additional, unrecited elements or method steps.
The term “or combinations thereof” as used herein refers to all permutations and combinations of the listed items preceding the term. For example, “A, B, C, or combinations thereof” is intended to include at least one of: A, B, C, AB, AC, BC, or ABC, and if order is important in a particular context, also BA, CA, CB, CBA, BCA, ACB, BAC, or CAB. Continuing with this example, expressly included are combinations that contain repeats of one or more item or term, such as BB, AAA, AAB, BBC, AAABCCCC, CBBAAA, CABABB, and so forth. The skilled artisan will understand that typically there is no limit on the number of items or terms in any combination, unless otherwise apparent from the context.
As used herein, the term “substantially” means that the subsequently described event or circumstance completely occurs or that the subsequently described event or circumstance occurs to a great extent or degree. For example, the term “substantially” means that the subsequently described event or circumstance occurs at least 90% of the time, or at least 95% of the time, or at least 98% of the time.
As used herein, the phrase “associated with” includes both direct association of two moieties to one another as well as indirect association of two moieties to one another. Non-limiting examples of associations include covalent binding of one moiety to another moiety either by a direct bond or through a spacer group, non-covalent binding of one moiety to another moiety either directly or by means of specific binding pair members bound to the moieties, incorporation of one moiety into another moiety such as by dissolving one moiety in another moiety or by synthesis, and coating one moiety on another moiety.
The term “liquid test sample” as used herein will be understood to include any type of biological fluid sample that may be utilized in accordance with the presently disclosed and claimed inventive concept(s). Examples of biological samples that may be utilized include, but are not limited to, whole blood or any portion thereof (i.e., plasma or serum), saliva, sputum, cerebrospinal fluid (CSF), intestinal fluid, intraperotineal fluid, cystic fluid, sweat, interstitial fluid, tears, mucus, urine, bladder wash, semen, combinations, and the like. As used herein, the term “volume” as it relates to the liquid test sample utilized in accordance with the presently disclosed and claimed inventive concept(s) means from about 0.1 microliter to about 100 microliters, or from about 1 microliter to about 75 microliters, or from about 2 microliters to about 60 microliters, or less than or equal to about 50 microliters.
The term “patient” includes human and veterinary subjects. In certain embodiments, a patient is a mammal. In certain other embodiments, the patient is a human. “Mammal” for purposes of treatment refers to any animal classified as a mammal, including human, domestic and farm animals, nonhuman primates, and zoo, sports, or pet animals, such as dogs, horses, cats, cows, etc.
Turning now to particular embodiments, the presently disclosed and claimed inventive concept(s) relate to a device(s), kit(s), and method(s) for dispensing at least two liquid reagents for use in analyte(s) detection assays. More specifically, the presently disclosed and claimed inventive concept(s) relate to a modified apparatus present within a reaction cassette and/or housing that is capable of dispensing at least two liquid reagents for use in analyte(s) detection assays, as well as kits and methods of use related thereto.
It is contemplated that virtually any reagent used in the fields of biological, chemical, or biochemical analyses and assays could be used in the devices, kits, and methods of the presently claimed and disclosed inventive concept(s). It is contemplated that these reagents may undergo physical and/or chemical changes when bound to an analyte of interest whereby the intensity, nature, frequency, or type of signal generated by the reagent-analyte complex is directly proportional or inversely proportional to the concentration of the analyte existing within the fluid sample. These reagents may contain indicator dyes, metal, enzymes, polymers, antibodies, and electrochemically reactive ingredients and/or chemicals that, when reacting with an analyte(s) of interest, may exhibit change in color.
Any method of detecting and measuring the analyte in a fluid sample can be used in the devices, kits, and methods of the presently claimed and inventive concepts. A variety of assays for detecting analytes are well known in the art and include, but are not limited to, chemical assays, enzyme inhibition assays, antibody stains, latex agglutination, latex agglutination inhibition and immunoassays, such as, radioimmunoassays. The term “antibody” herein is used in the broadest sense and refers to, for example, intact monoclonal antibodies, polyclonal antibodies, multi-specific antibodies (e.g., bispecific antibodies), and to antibody fragments that exhibit the desired biological activity (e.g., antigen/analyte-binding). The antibody can be of any type or class (e.g., IgG, IgE, IgM, IgD, and IgA) or sub-class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2).
While immunoassays (including, but not limited to, sequential analytical chemical and immunoassays) are primarily discussed herein for the detection of at least one analyte of interest present in a liquid test sample, a person having ordinary skill in the art should readily understand that the presently disclosed and claimed inventive concept(s) are not strictly limited to immunoassays and may include, by way of example and not by limitation, chemical and chemical-based assays, nucleic acid assays, lipid-based assays, and serology-based assays. Immunoassays, including radioimmunoassays and enzyme-linked immunoassays, are useful methods for use with the presently claimed and disclosed inventive concepts. A variety of immunoassay formats, including, for example, competitive and non-competitive immunoassay formats, antigen/analyte capture assays and two-antibody sandwich assays can be used in the methods of the invention. Enzyme-linked immunosorbent assays (ELISAs) can be used in the presently claimed and disclosed inventive concepts, as well. In the case of an enzyme immunoassay, an enzyme is typically conjugated to a second antibody, generally by means of glutaraldehyde, periodate, hetero-bifunctional crosslinking agents, or biotin-streptavidin complexes. As will be readily recognized, however, a wide variety of different conjugation techniques exist which are readily available for use with the presently disclosed and claimed inventive concept(s) to one skilled in the art.
Assays, including, but not limited to, immunoassays, nucleic acid capture assays, lipid-based assays, and serology-based assays, can be developed for a multiplexed panel of proteins, peptides, and nucleic acids which may be contained within a liquid test sample, with such proteins and peptides including, for example but not by way of limitation, albumin, microalbumin, cholesterol, triglycerides, high-density lipoproteins, low-density lipoproteins, hemoglobin, myoglobin, α-1-microglobin, immunoglobins, enzymes, proteins, glycoproteins, protease inhibitors, drugs, cytokines, creatinine, and glucose. The device(s), kit(s), and method(s) disclosed and/or claimed herein may be used for the analysis of any fluid sample, including, without limitation, whole blood, plasma, serum, or urine.
Referring now to
The reaction cassette/housing 40 comprises a body 42 formed by the top perimeter side 43, a bottom perimeter side 44, a first perimeter side 46, a second perimeter side 48, and a bottom portion 50. The reaction cassette 40 further comprises a top portion 52 that is used to seal the body 42 of the reaction cassette 40 after the liquid reagent container 70 containing at least one diagnostic assay buffer(s) and/or liquid assay reagent(s) has been incorporated into the reaction cassette 40 as described and/or claimed herein. Such seal can be accomplished via any method commonly known in the art, including, without limitation, adhesive(s), glue, sonic welding, laser welding, and/or any permanent fastener(s).
In one embodiment, the body 42 of the reaction cassette 40 is constructed such that the body is formed via the connection of the top perimeter side 43, the bottom perimeter side 44, the first perimeter side 46, and the second perimeter side 48 to the bottom portion 50. Such connection can be via any method commonly known in the art, including, without limitation, adhesive(s), glue, sonic welding, laser welding, and/or any permanent fastener(s). In another embodiment, the body 42 can be constructed such that the top perimeter side 43, the bottom perimeter side 44, the first perimeter side 46, the second perimeter side 48, and the bottom portion 50 is one contiguous piece, for instance, by way of example only, one contiguous piece of plastic.
The reaction cassette 40 has a substantially horizontal axis of rotation. While the external dimensions of the reaction cassette 40 are not critical, in one non-limiting embodiment of the presently disclosed and/or claimed inventive concept(s), the reaction cassette 40 has a height and width of about 3 centimeters to about 15 centimeters and a thickness of about 0.25 centimeters to about 2 centimeters. In one embodiment, the dimensions of the reaction cassette 40 comprise a height and width of about 6 centimeters and a thickness of about 1 centimeter.
In one non-limiting embodiment, the body 42 of the reaction cassette 40 further comprises a first inner wall 58 and a second inner wall 59, wherein the first inner wall 58 and the second inner wall 59 extend downward from the top perimeter wall 43 and are positioned opposite of one another and substantially perpendicular to the top perimeter wall 43 and the bottom perimeter wall 44. The first perimeter side 46, together with the second perimeter side 48, the bottom portion 50, and the top portion 52 form a reaction chamber 56, a portion of which is U-shaped and formed by a third inner wall 61 which extends between and substantially perpendicular to the second inner wall 59 and the second perimeter side 48. The reaction chamber 56 is in fluid communication with the inlet 54, thereby allowing a liquid test sample (not shown) to be introduced via the capillary 80 into the reaction chamber 56 of the reaction cassette 40. Once the body 42 of the reaction cassette 40 has been sealed by the top portion 52 following the incorporation of the liquid reagent container 70 into the reaction cassette 40, an inlet 54 is thereby formed between the first perimeter side 46 and the first side wall 58, the inlet 54 being substantially parallel to the first perimeter side 46 and the first side wall 58 and extending from the top perimeter side 43 downward toward the bottom perimeter side 44 of the reaction cassette 40. The inlet 54 is capable of securely receiving the capillary 80 such that the liquid test sample (not shown) is introduced from the capillary 80 into the reaction chamber 56 of the reaction cassette 40. While a capillary 80 is shown in the Figures as introducing the liquid test sample (not shown) into the reaction chamber 56 of the reaction cassette 40, it should be readily understood to a person having ordinary skill in the art that the liquid test sample (not shown) can be introduced into the reaction cassette 40 via any device capable of introducing a liquid a test sample, including, by way of example and not by way of limitation, a pipette(s). In addition, the inlet 54 can be stoppered, plugged, or otherwise closed subsequent to the introduction of the liquid test sample into the reaction cassette 40 so as to prevent liquid loss during the course of the methodologies described herein, including, but not limited to, assays, including immunoassays.
With specific reference to the liquid reagent container 70, while the figures depict embodiments of the liquid reagent container 70 as comprising a single cavity 75 (shown in
Referring now to
In one embodiment and as shown in
In one non-limiting embodiment of the presently disclosed and/or claimed inventive concept(s), the first solid reaction zone 65 comprises an oxidant (such as, for example, ferricyanide) which, as described in further detail hereinbelow, may be formulated, manufactured, and/or combined with at least one dye, the at least one dye having a known extinction coefficient when interrogated by particular wavelength(s) of light.
The second solid reaction zone 66 and the third solid reaction zone 68 comprise an agglutinator and an antibody-latex (for instance, by way of example only, a glycated hemoglobin A1c antibody), respectively. However, it should be readily understood to a person having ordinary skill in the art, that any compound, composition, and/or molecule can be used on the solid reagent zones in order to accomplish the presently disclosed and/or claimed inventive concept(s), including, without limitation, detection of at least one analyte(s) of interest present in a liquid test sample. In addition, it should be understood to a person having ordinary skill in the art that the presently disclosed and/or claimed inventive concept(s) can be accomplished in the absence of any or all of the first solid reagent zone 65, the second solid reagent zone 66, and the third solid reagent zone 68. In such an instance, the at least one liquid reagent/buffer 75A is capable of detecting at least one analyte(s) present in a liquid test sample in the absence of one or all of the solid reagent zones 65, 66, and/or 68.
With respect to the third solid reagent zone 68, and as discussed in greater detail hereinbelow, in one non-limiting embodiment, the third solid reagent zone 68 comprises and/or consists of one or more highly-concentrated sugars combined with at least one hydrophilic polysaccharide.
Referring now to
It is to be understood that
An illustrative, non-limiting method of using the reaction cassette 40 depicted in
In one embodiment, the first step is to provide the reaction cassette 40 into a holder mechanism of a diagnostic instrument, apparatus, or system such that a second corner 74 of the reaction cassette 40, which is formed by the substantial perpendicular intersection of the second perimeter side 48 and the bottom perimeter side 44, is positioned in a downward orientation. Following insertion of the reaction cassette 40 into the suitable instrument, apparatus, or system, a liquid test sample (not shown) is drawn into the capillary 80 and the capillary 80 containing the liquid test sample is inserted into inlet 54 whereby the liquid test sample contained in the capillary 80 is proximally located near a first corner 72 of the reaction cassette 40. Upon insertion of the capillary 80 into the inlet 54 of the reaction cassette 40, the capillary 80 seals the inlet 54 of the reaction cassette 40. The portion of the capillary 80 near the first corner 72 is configured such that when the capillary 80 is positioned as described above, the portion of the capillary 80 containing the liquid test sample is capable of being contacted by a liquid in the reaction chamber 56, such as the liquid reagent/buffer 75A introduced into the reaction chamber 56 from the at least one cavity 75 of the liquid reagent container 70.
As shown in
As shown in
Where the first reaction mixture 76 provides one or more detectable responses or measureable characteristics (for instance, by way of example only, a first absorbance and a second absorbance) which is required or desired to be measured according to a particular assay protocol, as shown in
As depicted in
While not shown in the Figures, the analytical research kit 10 may then be rotated counter-clockwise such that the second reaction mixture 79 is transported via gravity from the third corner 78 to the sample read window 64 in the second corner 74, provided that, in one embodiment. Any such second detectable response provided by the second reaction mixture 79 can then be measured, and the remaining assay steps, if necessary, can be carried out subsequent thereto. By way of example only and not by way of limitation, the second detectable response may be a glycated hemoglobin (HbA1c) measurement where the liquid test sample is whole blood, for example, such as when performing an assay for the percent of glycated hemoglobin (HbA1c) in a whole blood sample. In the case of a lipid-based assay, the second detectable response may be a high-density lipoprotein (HDL) cholesterol measurement where the liquid test sample is blood serum, for example, when performing an assay for the calculation of the percent of low-density lipoprotein (LDL) cholesterol present in a blood serum sample.
As previously mentioned, in one non-limiting embodiment the third solid reagent (for instance, by way of example, an antibody latex reagent) present on and/or in the third solid reagent zone 68 comprises and/or consists of one or more highly-concentrated sugars. Due to the high concentration of sugar, when the third solid reagent is dried (for instance, by way of example only, via conduction and/or convection drying procedure(s)) to form the mesa/node of the third solid reagent zone 68, the third solid reagent exhibits low tensile strength and has a tendency to fracture over time. As shown in
As shown in
Referring now to
In one non-limiting embodiment, the third solid reagent is a dried antibody latex reagent comprising gelatin and at least one sugar utilized for the detection of glycated hemoglobin present in the second reaction mixture 79. By way of example only, the at least one sugar may comprise and/or consist of monosaccharides, disaccharides, and/or sugar alcohols, including, without limitation, fructose, galactose, glucose, cellobiose, lactose, lactulose, maltose, sucrose, trehalose, mannitol, and combinations thereof.
In one non-limiting embodiment of the presently disclosed and/or claimed inventive concept(s), the third solid reagent is a dried antibody latex reagent comprised of a combination gelatin, sucrose, and trehalose and an antibody for the detection of glycated hemoglobin in the second reaction mixture 79. In this latter embodiment, when only one of the sugars is utilized, fractures (i.e., phenotypic changes in the mesa/node comprising the third solid reaction zone 68) occur at a higher frequency and at a greater severity. In addition, in this latter embodiment, it has been found that shifting away from the current ratio of trehalose to sucrose (such as, by way of example only, a ratio of trehalose to sucrose of about 7.5% and 7.5% to about 10 microliters of dispensed reagent) further increases the rate of fracturing of the mesa/node.
In one non-limiting embodiment of the presently disclosed and/or claimed inventive concept(s), the fracturing and phenotypic changes related to the mesas/nodes of the third solid reagent zone 68 comprising a dried antibody latex reagent, gelatin, and at least one monosaccharide, disaccharide, sugar alcohol, and/or combinations thereof are formulated with a predetermined concentration of at least one hydrophilic polysaccharide. The at least one hydrophilic polysaccharide acts as a surface and bond stabilizer to the gelatin and/or at least one monosaccharide, disaccharide, sugar alcohol, or combination thereof to thereby reinforce the node/mesa to mitigate or eliminate fracturing and phenotypic changes to the mesa/node. In one non-limiting embodiment, such at least one hydrophilic polysaccharide comprises, consists of, or is selected from the group consisting of cellulose, carboxymethylcellulose (CMC), FICOLL® (neutral, highly-branched, high-mass hydrophilic polysaccharide, GE Healthcare Bioscience AB, Uppsala, Sweden), starch, pullulan, maltodextrin, chitosan, chitin, dextran, arabinogalactan, and/or any combination thereof. In one non-limiting embodiment, that at least one hydrophilic polysaccharide is sodium carboxymethylcellulose.
In addition to or in lieu of at least one hydrophilic polysaccharide, at least one hydrophilic non-saccharide-based polymer may be utilized in accordance with the presently disclosed and/or claimed inventive concept(s) to stabilize the mesa/node of the third solid reagent zone 68. In one non-limiting embodiment, such at least one hydrophilic non-saccharide-based polymer comprises, consists of, or is selected from the group consisting of poly(N-isopropylacrylamide) (PNIPAM), polyacrylamide, poly(2-oxazoline), polyethylenimine, poly(acrylic acid), polymethyacrylate, acrylic-based polymers, poly(ethylene glycol), poly(ethylene oxide), poly(vinyl alcohol) (PVA), poly(vinylpyrrolidone) (PVP), polyelectrolytes, cucurbituril hydrate, collagen, lignin, and combination thereof.
As previously discussed herein, in one non-limiting embodiment, the addition of a concentration of the hydrophilic polysaccharide carboxymethylcellulose (CMC) to the dried reagent comprising gelatin and at least one monosaccharide, disaccharide, and/or sugar alcohol present in or on the mesa/node of the third solid reaction zone 68 thereby stabilizes the mesa/node and mitigates or eliminates fracturing and phenotypic changes to such mesa/node.
Referring now to
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Referring now to
Referring now to
An analytical reaction kit, the kit comprising: a reaction cassette for conducting at least one diagnostic assay, the reaction cassette comprising: a body, the body comprising a top perimeter side, a bottom perimeter side, a first perimeter side, a second perimeter side, a bottom portion, and a top portion thereby forming a reaction cassette chamber; an inlet for introducing a liquid test sample into the reaction cassette chamber; and a reaction chamber in liquid communication with the inlet, wherein the reaction chamber further comprises at least one solid reagent zone, wherein the at least one solid reagent zone comprises at least one antibody reagent zone for the detection of at least one analyte of interest present in a patient's liquid test sample, the at least antibody reagent zone comprises at least one antibody, at least one monosaccharide, disaccharide, sugar alcohol, or combinations thereof, and at least one hydrophilic polysaccharide; a liquid analytical reagent dispensing apparatus, the apparatus comprising: a container having a first end, a second end, a first side, a second side, a bottom side, a top side, a cavity being open at the top side of the container, and a flange extending around the open top of the cavity, at least one liquid reagent disposed within the cavity; and a flexible cover removably affixed to the flange of the container to seal the at least one liquid reagent in the cavity, wherein the at least one liquid reagent flows from the cavity into the reaction chamber upon removal of the flexible cover from the flange and with the first end of the container positioned substantially vertically beneath the second end of the container; and a capillary, the capillary capable of being partially inserted into the inlet of the reaction cassette to thereby introduce a liquid test sample into the reaction chamber.
An analytical reaction kit, the kit comprising: a housing for conducting at least one diagnostic assay, wherein the housing comprises a reaction chamber for the conductance of one or more diagnostic assays, the reaction chamber further comprising at least one solid reagent zone, wherein at least one of the at least one solid reagent zone comprises an antibody reagent zone for the detection of at least one analyte of interest present in a patient's liquid test sample, the antibody reaction zone comprising at least one antibody, at least one monosaccharide, disaccharide, sugar alcohol, or combinations thereof, and at least one hydrophilic polysaccharide; and a liquid analytical reagent dispensing apparatus contained within the housing, the apparatus comprising: a container, wherein the container contains at least one liquid analytical reagent, the container being in fluid communication with the reaction chamber to thereby dispense the at least one liquid analytical reagent at a predetermined time.
The analytical reaction kit, wherein the liquid test sample is a volume of whole blood.
The analytical reaction kit, wherein the volume of whole blood is in a range of from about 0.1 microliter to about 100 microliters.
The analytical reaction kit, wherein the one or more diagnostic assays are selected from a total hemoglobin detection assay, a glycated hemoglobin detection assay, and combinations thereof.
The analytical reaction kit, wherein the at least one analyte of interest is glycated hemoglobin.
The analytical reaction kit, wherein the at least one antibody comprises a glycated hemoglobin detection antibody.
The analytical reaction kit, wherein the at least one monosaccharide is selected from the group consisting of fructose, galactose, glucose, and combinations thereof.
The analytical reaction kit, wherein the at least one disaccharide is selected from the group consisting of cellobiose, lactose, lactulose, maltose, sucrose, trehalose, and combinations thereof.
The analytical reaction kit, wherein the at least one sugar alcohol comprises mannitol.
The analytical reaction kit, wherein the at least one hydrophilic polysaccharide is selected from the group consisting of cellulose, carboxymethylcellulose, FICOLL, starch, pullulan, maltodextrin, chitosan, chitin, dextran, arabinogalactan, and combinations thereof.
A method for mechanically stabilizing at least one solid reagent zone for use in at least one diagnostic assay, the method comprising the steps of: forming at least one solid reagent zone precursor, wherein the solid reagent zone precursor comprises at least one monosaccharide, disaccharide, sugar alcohol, or combinations thereof in liquid state; adding a predetermined concentration of at least one hydrophilic polysaccharide to the at least one solid reagent precursor; and drying the at least one solid reagent precursor to thereby form at least one stabilized solid reagent zone for use in the conductance of one or more diagnostic assays.
The method, wherein the at least one monosaccharide is selected from the group consisting of dextrose, fructose, galactose, glucose, and combinations thereof.
The method, wherein the at least one disaccharide is selected from the group consisting of cellobiose, lactose, lactulose, maltose, sucrose, trehalose, and combinations thereof.
The method, wherein the at least one sugar alcohol is mannitol.
The method, wherein the at least one hydrophilic polysaccharide is selected from the group consisting of cellulose, carboxymethylcellulose, FICOLL, starch, pullulan, maltodextrin, chitosan, chitin, dextran, arabinogalactan, and combinations thereof.
The method, wherein the one or more diagnostic assays is selected from a total hemoglobin detection assay, a glycated hemoglobin detection assay, and combinations thereof.
The method, wherein the stabilized solid reagent zone further comprises at least one antibody for the detection of at least one analyte of interest present in a patient's liquid test sample.
The method, wherein the at least one antibody comprises a glycated hemoglobin antibody.
The method, wherein the at least one analyte of interest is glycated hemoglobin.
The method, wherein the patient's liquid test sample is a volume of whole blood.
The method, wherein the predetermined concentration of the at least one hydrophilic polysaccharide is in a range of from about 0.5 milligrams per milliliter to equal to about 5.5 milligrams per milliliter.
Thus, in accordance with the presently disclosed and claimed inventive concept(s), there have been provided devices, kits, and methods for dispensing at least two liquid reagents for use in analyte(s) detection assays. As described herein, the presently disclosed and claimed inventive concept(s) relate to embodiments of a modified solid reaction zone for the conductance of at least one diagnostic assay, as well as kits and method related thereto. More specifically, as described herein, the presently disclosed and/or claimed inventive concept(s) relate to non-limiting embodiments of apparatus, kits, and methods for the incorporation of at least one hydrophilic polysaccharide to dried sugar reagents present in or on a solid reaction zone and/or a mesa/node thereof to thereby increase the mechanical stability of such solid reaction zone and to increase the accuracy of results obtained from the conductance of at least one diagnostic assay due to the reduction or elimination of fracturing of such solid reaction zone (for instance, an latex antibody reaction zone). Accordingly, the present disclosed and/or claimed inventive concept(s) fully satisfy the objectives and advantages set forth hereinabove. Although the presently disclosed and claimed inventive concept(s) has been described in conjunction with the specific drawings, experimentation, results and language set forth hereinabove, it is evident that many alternatives, modifications, and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the presently disclosed and claimed inventive concept(s).
The present patent application claims the benefit of provisional patent application Ser. no. 62/813,297, filed on Mar. 4, 2019, the entire contents of which are hereby incorporated herein by reference.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US2020/019840 | 2/26/2020 | WO | 00 |
| Number | Date | Country | |
|---|---|---|---|
| 62813297 | Mar 2019 | US |
