Disposable flow-through diagnostic devices and methods of construction thereof

Abstract

The disposable diagnostic device (10) includes a body (12) having a first flow path (14) and a second flow path (16) spaced from the first flow path. A bulge (18) is operably secured to the body and encloses a chamber. The chamber is configured in a sealed sealed relationship from the first and second flow paths when the device is in a first unactivated state and in open communication with at least one of the first and second flow paths when the device is in a second activated state. A reactant (22) and an inert gas (24) are disposed within the chamber, whereby the inert gas protects the reactant from exposure to contaminants when the device is in the first unactivated state. Methods of constructing the disposable diagnostic device are also disclosed.

Description

Cross-reference to related applications

[0001] This application claims priority from U.S. Application No. 63 / 218,250, filed July 2, 2021, the disclosure of which is incorporated herein by reference. [Technical Field]

[0002] The present invention relates generally to in vitro diagnostics, and more particularly to a disposable diagnostic cartridge that includes labile contents within a compartment thereof, and a method for constructing a disposable diagnostic cartridge having such labile contents therein. [Background technology]

[0003] Diagnostic tests are increasingly being used to determine the state and condition of biological environments, including, by way of example and not limitation, human health care, agriculture, livestock management, municipal systems management, and national defense. New markets are emerging in which diagnostic tests are performed at the point-of-care. Diagnostic tests can be complex and require multiple reagents and multiple steps to perform an assay. An assay is a series of steps or procedures used to measure the presence or absence of a substance in a sample, the amount of a substance in a sample, or a characteristic of a sample. One example of a common and relatively simple on-site assay is a blood glucose test, which can be easily performed by a layperson. In this test, blood is typically mixed with glucose oxidase, which reacts with the glucose in the sample to produce gluconic acid, which then reacts with a chemical (typically ferricyanide) to produce ferrocyanide. A current is passed through the ferrocyanide, and its impedance reflects the amount of glucose present.

[0004] The blood glucose assays described above are relatively common and simple. However, many assays are far more complex in that they require the mixing of highly valuable and unstable reactants with fluid or gaseous reagents that are sensitive to gases, such as moisture and / or oxygen, commonly present in the ambient environment, to perform the test and provide the desired quantitative test results. Known unstable reactants include lyophilized reagents and gases, such as CO2, that contain radioactive carbon isotopes. Given the labile nature of such reactants, it is important to ensure that the selected reactants are protected from exposure to environmental contaminants before and during use to avoid causing reactant decomposition and ultimately compromising the assay results.

[0005] To avoid degradation of labile reactants contained in known diagnostic test devices, it is common to incorporate the labile reactants into the diagnostic test device in a dry room environment. While a dry room environment, typically a controlled environment with a moisture content of 15% or less, is useful, workers in dry room environments are generally required to use respirators to avoid lung harm. Thus, operating, maintaining, and working in a dry room environment can be cumbersome and costly.

[0006] In addition to the requirement that the aforementioned diagnostic test devices be assembled in a dry-room environment, it is common for the assembled diagnostic test device to be packaged in a sealed package having a controlled internal environment (typically controlled through the incorporation of moisture absorbents to prevent moisture within the sealed package and the surrounding environment from causing decomposition of labile reactants). If such precautions are not taken when packaging diagnostic test devices, the risk of decomposition of labile reactants is significantly increased. Even with such packaging precautions, the viable shelf life of a diagnostic test device can be relatively short, such as a few weeks, especially in environments where the temperature and / or moisture content are not controlled. Summary of the Invention

[0007] In accordance with one object of the present invention, a single-use, disposable diagnostic cartridge is provided that addresses at least the above-mentioned problems associated with known single-use, disposable diagnostic cartridges.

[0008] According to one aspect of the present invention, a disposable diagnostic device is provided. The disposable diagnostic device includes a body having a first flow path and a second flow path spaced from the first flow path. A shroud is operably secured to the body. The shroud encloses a chamber, and the chamber is configured to be in a sealed relationship with the first and second flow paths when the disposable diagnostic device is in a first, unactivated state. The chamber is configured to be in open communication with at least one of the first and second flow paths when the disposable diagnostic device is in a second, activated state. A reactant is disposed within the chamber, and an inert gas is disposed within the chamber. The inert gas protects the reactant from exposure to contaminants within the chamber while the disposable diagnostic device is in the first, unactivated state.

[0009] moreover The first flow path is sealed off from the chamber by a first rupturable member covering a first port when the first rupturable member is in an unruptured state, and the first flow path is in fluid communication with the chamber through the first port when the first rupturable member is in a ruptured state; the second flow path is sealed off from the chamber by a second rupturable member covering a second port when the second rupturable member is in an unruptured state, and the second flow path is in fluid communication with the chamber through the second port when the second rupturable member is in a ruptured state.

[0010] According to another aspect, the first rupturable member is secured to the body and the second rupturable member is secured to the body.

[0011] According to another aspect, the first rupturable member and the second rupturable member are a single piece of material.

[0012] According to another aspect, the system further includes a stirring mechanism disposed within the chamber configured to stir a flow of medium entering the chamber from one of the first flow path through the first port and the second flow path through the second port to mix the medium with the reactant.

[0013] According to another aspect, the stirring mechanism is formed on an inner surface of the shroud, the inner surface being exposed to the chamber.

[0014] According to another aspect, the interior surface has a plurality of projections extending into the chamber to form the stirring mechanism.

[0015] According to another aspect, the stirring mechanism is formed by one or more solid members housed within the chamber, the one or more solid members being freely movable within the chamber when at least one of the first and second rupturable members is in the ruptured state to mix the medium with the reactant.

[0016] According to another aspect, when the first and second rupturable members are in the unruptured state, the one or more solid members are restrained against movement within the chamber.

[0017] According to another aspect, the stirring mechanism is formed by a ferrous material contained within the chamber, the ferrous material configured to move within the chamber upon selective exposure to an external magnetic field.

[0018] According to another aspect, the shroud is formed of a flexible material configured to be pressed substantially flat to facilitate flow of medium into the chamber from one of the first flow path through the first port and the second flow path through the second port and out the other of the first flow path through the first port and the second flow path through the second port.

[0019] According to another aspect, the shroud has a compressed state that defines a first volume within the chamber when the first rupturable member is in its unruptured state and the second rupturable member is in its unruptured state, and an expanded state that defines a second volume within the chamber when the first rupturable member is in its ruptured state or the second rupturable member is in its ruptured state, the second volume being greater than the first volume.

[0020] According to another aspect, a method for constructing a disposable diagnostic device is provided, the method comprising: a first flow path and a second flow path spaced from the first flow path; Multiple microfluidic channels a first rupturable member covering the first port, and a second rupturable member covering the second port. providing a diagnostic cartridge body having: providing a shroud; disposing a reactant between the shroud and the diagnostic cartridge body; and securing the shroud to the diagnostic cartridge body so as to seal a chamber between the shroud and the diagnostic cartridge body, the reactant contained within the chamber, the chamber configured to be in selective fluid communication with the plurality of microfluidic channels; The placing step and the fixing step are carried out in a vacuum atmosphere. This includes: the first flow path is sealed from the chamber by the first rupturable member when the first rupturable member is in an unruptured state, and the first flow path is in fluid communication with the chamber through the first port when the first rupturable member is in a ruptured state; The second flow path is sealed from the chamber by the second rupturable member when the second rupturable member is in an unruptured state, and the second flow path is in fluid communication with the chamber through the second port when the second rupturable member is in a ruptured state. .

[0021] According to another aspect, the method includes providing an inert gas into the vacuum atmosphere and sealing a portion of the inert gas in the chamber along with the reactants.

[0022] According to another aspect, the method performs the fastening step without a dry room atmosphere.

[0023] According to another aspect, the method can further include providing a stirring mechanism within the chamber to facilitate mixing of the reactants with the reagents. [Brief explanation of the drawings]

[0024] These and other aspects, features and advantages of the present invention will be more readily understood when considered in conjunction with the following detailed description of the presently preferred embodiments and best mode, the appended claims and the accompanying drawings. [Figure 1] 1 is a perspective view of a disposable diagnostic device constructed in accordance with one aspect of the present invention. [Figure 2] 2 is a cross-sectional view of the disposable diagnostic device taken generally along line 2-2 of FIG. 1. [Figure 3] FIG. 3 is a view similar to FIG. 2 showing the disposable diagnostic device in operation. [Figure 3a] FIG. 4 is an enlarged view of the boxed area 3a of FIG. 3 illustrating the inlet. [Figure 3b] 3b is an enlarged view of the boxed area 3b of FIG. 3 illustrating the outlet, and is similar to FIG. 3a in enlarged operational illustration. [Figure 4] 2 is a view similar to FIG. 1 of a disposable diagnostic device constructed in accordance with another embodiment of the present invention. [Figure 5] 5 is a cross-sectional view of the disposable diagnostic device of FIG. 4 taken generally along line 5-5. [Figure 5a] 6 is a cross-sectional view similar to FIG. 5 of a disposable diagnostic device according to another embodiment of the present invention. [Figure 5b] 5b is a view similar to FIG. 5a of the disposable diagnostic device, showing the disposable diagnostic device of FIG. 5a in a partially activated state. [Figure 6] 5 of the disposable diagnostic device, showing the disposable diagnostic device of FIG. 4 in operation. [Figure 7] 1, but is a view similar to FIG. 1 of a shroud assembly for a disposable diagnostic device constructed in accordance with another embodiment of the present invention. [Figure 8]8 is a cross-sectional view of the disposable diagnostic device assembled with the shroud assembly of FIG. 7 taken generally along line 8-8. DETAILED DESCRIPTION OF THE INVENTION

[0025] Referring more particularly to the drawings, FIG. 1 illustrates a disposable diagnostic device (also referred to as a diagnostic cartridge, hereinafter also referred to as cartridge 10) constructed in accordance with one embodiment of the present invention for use in performing assays in the qualitative and quantitative analysis of analytes. Cartridge 10 includes a body 12 having a first microfluidic flow path (hereinafter referred to as first flow path 14) for conveying fluids and / or gases and a second microfluidic flow path (hereinafter referred to as second flow path 16) for conveying fluids and / or gases, with first flow path 14 spaced from second flow path 16 by a reservoir chamber (hereinafter simply referred to as chamber 20), which may also function as a mixing chamber. Body 12 may optionally be configured with upper and lower body portions 12a and 12b secured together to facilitate the formation of desired contours and flow paths therein. By way of example, first and second flow paths 14 and 16 are shown formed in lower body portion 12b and enclosed by upper body portion 12a. A blister, also referred to as a shroud 18, is operably secured to the generally planar surface of the upper body portion 12a. The shroud 18 encloses a chamber 20, which is configured to be sealed off from the first and second flow paths 14, 16 when the disposable diagnostic device 10 is in an inactive state (also referred to as an inactive first state). The chamber 20 is configured to be in open communication (meaning that fluids and / or gases can flow freely therebetween) with at least one of the first and second flow paths 14, 16 when the disposable diagnostic device 10 is in an operatively configured, operative state (also referred to as an activated second state). A reactant 22, e.g., a labile reactant such as a biological enzyme, a lyophilized reagent containing a nucleic acid sequence, a radioactive carbon isotope, or any other form of sensitive biological material, is disposed within the chamber 20 along with an inert gas 24. An inert gas 24, such as argon, for example and without limitation, occupies the entire volume of the chamber 20 and protects the labile reactants 22 from exposure to fluid, solid and / or gaseous contaminants, such as oxygen, while within the chamber 20 when the disposable diagnostic device 10 is in its inactive first state.Thus, reactants 22 are protected from unintentional decomposition and degradation while stored within cartridge 10 for use in future performances of the assay as intended. With chamber 20 hermetically sealed from first flow path 14, second flow path 16, and ambient environment E by shroud 18, cartridge 10 is suitable for shipping and storage for extended periods of time, such as several years, without the need for additional protective features, including desiccants, or special packaging.

[0026] The cartridge 10 is easily manufactured without the need for a dry room environment, thus significantly reducing the overall cost of manufacture (including time, labor, space, capital equipment, etc.) compared to cartridges that require the use of a dry room environment for manufacturing. According to one embodiment, the cartridge 10 is manufactured under a vacuum atmosphere, which protects the labile reactants 22 from exposure to moisture and other forms of contamination, such as oxygen, while they are disposed within the chamber 20 and hermetically sealed. According to one embodiment, the labile reactants 22 may be disposed within the chamber 20 prior to securing the shroud 18 to the body 12. An inert gas 24 occupies the vacuum atmosphere and is sealed in the chamber 20 along with the labile reactants 22 upon securing the shroud 18 to the body 12.

[0027] The shroud 18 may be formed of any suitable flexible, adaptable material or substance for bounding and sealing the chamber 20 of a predetermined volume. The shroud 18 includes, by way of example and not limitation, a bottom surface or layer 26 without a predefined rupturable or flexible valve or opening, and an upper layer 28. While the bottom surface 26 is described as having no valves or openings, it is contemplated that predetermined valves or openings may be formed in the bottom surface 26, if desired, although not required, as a result of the upper layer 28 having a plurality of openings, punctures, or piercing members 30 configured to form openings 32 in the bottom surface 26 over the first and second ports 34, 36 of the first and second flow paths 14, 16, respectively. The upper layer 28 may be formed of the same type of material as the bottom layer 26 or a different type of material, as desired. The top layer 28 is sufficiently sized so that fluid / gas disposed therein forms a spherically expanded portion bounding the reservoir chamber 20. Here, the top layer 28 is flexible and strong, thereby allowing the spherical portion to be pressed and actuated, if desired, to facilitate urging the flow of fluid / gas through one of the first and second flow paths 14, 16. The bottom and top layers 26, 28 may be bonded together around their respective outer peripheries via any suitable bonding process, such as a welding or adhesive process, with the labile reactant 22 and inert gas 24 disposed therebetween.

[0028] The first flow path 14 is sealed off from the chamber 20 by a first valve (also referred to as a first rupturable member 38) covering the first port 34 when the first rupturable member 38 is in an unruptured state. The first flow path 14 is in fluid communication with the chamber 20 through the first port 34 when the first rupturable member 38 is in a ruptured state. The second flow path 16 is sealed off from the chamber 20 by a second rupturable member 40 covering the second port 36 when the second rupturable member 40 is in an unruptured state. The second flow path 16 is in fluid communication with the chamber 20 through the second port 36 when the second rupturable member 40 is in a ruptured state. The first and second rupturable members 38, 40 can be selectively ruptured simultaneously with one another or separately at different times, as desired.

[0029] The first rupturable member 38 is secured to the body 12, and the second rupturable member 40 is secured to the body 12. The first and second rupturable members 38, 40 are configured in overlapping relationship with the first and second ports 34, 36. The first and second rupturable members 38, 40 may be formed as a single piece of material, such as formed by the material of the bottom layer 26. The first and second rupturable members 38, 40 are rupturable, such as, by way of example and not limitation, via the piercing member 30. The ruptured first and second rupturable members 38, 40 have openings 32 to place the first and second flow paths in fluid communication with the chamber 20 via the first and second ports 34, 36.

[0030] Upon selectively piercing at least one of the first and second rupturable members 38, 40 to form an opening 32 therein, a desired reagent 42 may be introduced through one of the corresponding flow paths having an open port, such as, but not limited to, through the first flow path 14 and into the chamber 20 through the first port 34. Once the reagent 42 is introduced into the chamber 20, the reagent 42 and the reactant 22 may be mixed together to initiate a desired assay within the chamber 20.

[0031] To promote homogeneous mixing of the reagents 42 and the reactants 22, an agitation mechanism 44 may be disposed within the chamber. The agitation mechanism 44 is configured to agitate the flow of medium, here the reagents 42, entering the chamber 20 to rapidly and thoroughly mix the reagents 42 with the reactants 22. The agitation mechanism 44 tends to establish a non-laminar flow of the reagents 42 as the reagents 42 flow adjacent to and against the agitation mechanism 44. The agitation mechanism 44 may be formed on the inner surface 46 of the shroud 18 (FIGS. 5 and 6), with the inner surface 46 directly exposed to the chamber 20. For example, the agitation mechanism 44 may be formed via a plurality of protrusions 44 extending into the chamber 20. The protrusions 44 are shown as forming an undulating profile with alternating peaks and valleys. Alternatively, the agitation mechanism 44 may be formed by one or more solid members 48 (FIGS. 2 and 3) housed within the chamber 20. The one or more solid members 48 are free to move within the chamber 20 when at least one of the first and second rupturable members 38, 40 is in a ruptured state to facilitate mixing of the reagent 42 and the reactant 22. When the first and second rupturable members 38, 40 are in their unruptured states, the one or more solid members 48 may be constrained against movement within the chamber 20. This constraining may be achieved by, by way of example and not limitation, adhering the solid members 48 to a surface within the cavity 20. This adhesion may be dissolved by the reagent 42 as it enters the cavity 20. Movement of the solid members 48 may be facilitated by gravity by simply tilting the cartridge 10 sufficiently to cause movement of the solid members 48.

[0032] According to a further embodiment, the stirring mechanism 44 may be formed of a ferrous material as illustrated with respect to a solid member 48, where the solid member 48 may have ferrous contents contained within the chamber 20. The ferrous material 48 is configured to move within the chamber 20 upon selective exposure to an external magnetic field 50, which may be positioned and oriented as desired to obtain the desired movement of the ferrous material 48 within the chamber 20.

[0033] 5a, a disposable diagnostic device 110 according to a further embodiment is illustrated, with the same reference numerals used to identify similar features. The cartridge 110 includes a shroud 18 that may be provided to have a compressed state that defines a minimum first volume V1 within the chamber 20 when the first rupturable member 38 is in its unruptured state and the second rupturable member 40 is in its unruptured state, whereby the cartridge 110 is in its unactivated state. The shroud 18 may further be configured to achieve an expanded, deployed state defining a second volume V2 within the chamber 20 when at least one of the first rupturable member 38 and the second rupturable member 40 is in its rupturable state (shown in FIG. 5b as the first rupturable member 38 being ruptured to allow ingress (flow) of the reagent 42 into the cavity 20 through the first flow path 14). Here, the second volume V2 is larger than the first volume V1. Thus, the ingress of the reagent 42 into the cavity 20 causes the shroud 18 and the cavity below it to expand, thereby creating the expanded state. The remaining first or second rupturable member 38, 40 may then be opened upon expansion of the cavity 20, with the reagent 42 and the reactant 22 mixed together within the cavity 20. This allows the mixture to be evacuated from the cavity 20 through the desired first or second flow path 14, 16 and the assay can continue as desired.

[0034] 7 and 8, a disposable diagnostic device 210 according to a further embodiment of the present invention is illustrated, with the cartridge 210 having similar features identified by similar reference numerals in FIG. 8. In view of the above discussion of the listed features, further discussion is not believed necessary.

[0035] The foregoing description of the embodiments has been provided for purposes of illustration and description. It is not intended to be exhaustive or to limit the scope of the disclosure or the claims. Individual elements or features of a particular embodiment are generally not limited to that particular embodiment, but, where applicable, may be interchangeable and used in selected embodiments even if not specifically shown or described. The same may also be varied in various ways. Such variations are not to be considered a departure from the present disclosure, and all such variations are intended to be included within the scope of the present disclosure and the claims, which ultimately define the scope of the present invention.

Claims

1. 1. A disposable diagnostic device comprising: a body having a first flow path and a second flow path spaced from the first flow path; a shroud operably secured to the body, the shroud enclosing a chamber, the chamber configured in a sealed, sealed relationship from the first flow path and the second flow path when the disposable diagnostic device is in a first, unactivated state, and the chamber in open communication with at least one of the first flow path and the second flow path when the disposable diagnostic device is in a second, activated state; a reactant disposed within the chamber; and an inert gas disposed within the chamber, the inert gas protecting the reactants from exposure to contaminants within the chamber while the disposable diagnostic device is in the first non-operated state; the first flow path is sealed off from the chamber by a first rupturable member covering a first port when the first rupturable member is in an unruptured state, and the first flow path is in fluid communication with the chamber through the first port when the first rupturable member is in a ruptured state; The second flow path is sealed off from the chamber by a second rupturable member covering a second port when the second rupturable member is in an unruptured state, and the second flow path is in fluid communication with the chamber through the second port when the second rupturable member is in a ruptured state. A disposable diagnostic device.

2. 10. The disposable diagnostic device of claim 1, The first rupturable member is secured to the body, and the second rupturable member is secured to the body. A disposable diagnostic device.

3. 3. The disposable diagnostic device of claim 2, The first rupturable member and the second rupturable member are a single piece of material. A disposable diagnostic device.

4. 10. The disposable diagnostic device of claim 1 further comprising: a stirring mechanism disposed within the chamber; The stirring mechanism is configured to stir a flow of medium entering the chamber from one of the first flow path through the first port and the second flow path through the second port to mix the medium with the reactant. A disposable diagnostic device.

5. 5. The disposable diagnostic device of claim 4, the stirring mechanism is formed on an inner surface of the shroud, The inner surface is exposed to the chamber. A disposable diagnostic device.

6. 6. The disposable diagnostic device of claim 5, The inner surface has a plurality of projections extending into the chamber to form the stirring mechanism. A disposable diagnostic device.

7. 5. The disposable diagnostic device of claim 4, The stirring mechanism is formed by one or more solid members contained within the chamber, the one or more solid members being freely movable within the chamber when at least one of the first rupturable member and the second rupturable member is in the ruptured state to mix the medium with the reactant. A disposable diagnostic device.

8. 8. The disposable diagnostic device of claim 7, When the first and second rupturable members are in the unruptured state, the one or more solid members are constrained against movement within the chamber. A disposable diagnostic device.

9. 5. The disposable diagnostic device of claim 4, the stirring mechanism is formed of an iron-based material housed in the chamber; The ferrous material is configured to move within the chamber upon selective exposure to an external magnetic field. A disposable diagnostic device.

10. 10. The disposable diagnostic device of claim 1, The shroud is formed of a flexible material configured to be pressed substantially flat to facilitate flow of medium into the chamber from one of the first flow path through the first port and the second flow path through the second port and out the other of the first flow path through the first port and the second flow path through the second port. A disposable diagnostic device.

11. 11. The disposable diagnostic device of claim 10, The shroud is a compressed state defining a first volume within the chamber when the first rupturable member is in its unruptured state and the second rupturable member is in its unruptured state; an expanded state defining a second volume within the chamber when the first rupturable member is in its ruptured state or when the second rupturable member is in its ruptured state; and The second volume is greater than the first volume. A disposable diagnostic device.

12. 1. A method of constructing a disposable diagnostic device, comprising: providing a diagnostic cartridge body having a plurality of microfluidic channels including a first channel and a second channel spaced from the first channel, a first rupturable member covering a first port, and a second rupturable member covering a second port; providing a shroud; disposing a reactant between the shroud and the diagnostic cartridge body; and securing the shroud to the diagnostic cartridge body so as to seal a chamber between the shroud and the diagnostic cartridge body, the reactant contained within the chamber, the chamber configured to be in selective fluid communication with the plurality of microfluidic channels; performing the placing and fixing steps in a vacuum atmosphere; the first flow path is sealed from the chamber by the first rupturable member when the first rupturable member is in an unruptured state, and the first flow path is in fluid communication with the chamber through the first port when the first rupturable member is in a ruptured state; The second flow path is sealed off from the chamber by the second rupturable member when the second rupturable member is in an unruptured state, and the second flow path is in fluid communication with the chamber through the second port when the second rupturable member is in a ruptured state. A method characterized by:

13. 13. The method of claim 12, An inert gas is supplied into the vacuum atmosphere, and a portion of the inert gas is sealed in the chamber together with the reactant. A method characterized by:

14. The method of claim 13 further comprising: Providing a stirring mechanism within the chamber to facilitate mixing of the reactants with the reagents A method characterized by:

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