Assay system comprising an assay device and a handheld disposable assay device for use with the assay device

Abstract

The assay system comprises an assay apparatus and a handheld single-use assay device for electromagnetic radiation (EMR) inspection of a sample. The assay device comprises a housing, a sample slide for raising from an initial lowermost sample introduction position to a final uppermost sample inspection position, and a built-in liquid reagent dispensing arrangement for dispensing liquid reagents on the sample slide. The assay apparatus automatically actuates the assay device and comprises an imaging arrangement for obtaining an image of the sample.

Description

Technical Field

[0001] The present invention relates to an assay system comprising an assay device and a handheld assay device for use with the assay device. Background Art

[0002] Co-owned PCT International Application No. PCT / IL2018 / 050671, entitled "Assay Devices and Assay Apparatus for Use Therewith," published as PCT International Publication No. WO 2018 / 235073 A1, discloses an assay device for performing an EMR examination of a sample along one or more examination lines by an assay device. The assay device includes a housing having a sample slide for placing a body sample thereon. The sample slide is designed to be pushed from a lowermost sample introduction position to an uppermost sample examination sample, where the sample slide presses the body sample against the lower side of the top surface of the housing. The body sample is preferably reacted with one or more liquid reagents, such as saline, potassium hydroxide, and the like, before examination after being placed on the sample slide. It is also preferred that a pH detection surface be smeared with the body sample to provide a pH reading for diagnostic purposes.

[0003] There is a need for assay systems for diagnostic purposes of body samples. Summary of the invention

[0004] The present invention is directed to an assay system for diagnostic purposes of a body sample. The assay system comprises a disposable handheld assay device for each preparation of a body sample for diagnostic purposes and an assay device for use with an interchangeable assay device for obtaining diagnostic information of the body sample for diagnostic purposes. The handheld assay devices are each intended for use with a disposable handheld sample collection tool, the handheld sample collection tool comprising a handle and a sample collection tip for obtaining a body sample from a body orifice or exposed body surface. Body orifices include, in particular, facial orifices, urethra, rectum, and vagina. Exposed body surfaces include, in particular, rashes, rashes, open wounds, lips, eyes, etc. The handheld assay device may be preassembled with the handheld sample collection tool, or alternatively the handheld sample collection tool may be provided separately.

[0005] The assay device comprises a longitudinal assay device centerline and a generally box-shaped sleeve housing having a sample slide, the sample slide preferably having two or more spatially discrete working surfaces disposed along the longitudinal assay device centerline. The working surfaces are preferably smeared with a body sample upon sliding withdrawal of a sample collection tool by the assay device. The working surfaces preferably comprise a pH detection surface for providing a pH reading.

[0006] The measuring device includes a built-in liquid reagent distribution arrangement for distributing at least one liquid reagent to a body sample applied to a working surface. The built-in liquid reagent distribution arrangement includes a barrel, a leading seal, a tail seal component, a liquid reagent between the leading seal and the tail seal component, and a liquid reagent distribution port for distributing liquid reagents to each working surface. The leading seal is displaced from a liquid reagent distribution front position to a liquid reagent distribution position along its barrel by a plunger. The built-in liquid reagent distribution arrangement may include different tail seal components. A tail seal component is intended to be displaced from a liquid reagent distribution front position in front of its liquid reagent distribution port along the barrel to a liquid reagent distribution position exceeding its liquid reagent distribution port. Another tail seal component is a stopcock, which is permanently disposed at its liquid reagent distribution port and is intended to be rotated from a closed position to an open position for distribution purposes. The built-in liquid reagent distribution arrangement may be designed to distribute different liquid reagents on body samples applied to two or more spatially discrete working surfaces so that liquid reagents do not cross-react. The built-in liquid reagent dispensing arrangement can be designed to dispense different liquid reagent volumes by adjusting the distance between the leading and trailing sealing components or by adjusting the length of the plunger.

[0007] The assay device needs to undergo the following two actuations after application of the body sample in order to be ready to examine its body sample for diagnostic purposes: first, the actuation of its built-in liquid reagent dispensing arrangement. And second, the linear raising of its sample slide from its lowermost sample introduction position to its uppermost sample inspection position. The sample slide raising can occur simultaneously with the liquid reagent dispensing or after the liquid reagent dispensing, provided that the liquid reagent dispensing ends before the sample slide raising ends.

[0008] The measuring device comprises a tray with a tray recess, and the tray recess is used to interchangeably receive a measuring device in which a body sample has been preferably applied to its sample slide. The measuring device comprises one or more plungers for actuating the built-in liquid reagent dispensing arrangement of the handheld measuring device, and one or more sample slide elevation components for raising the sample slide of the handheld measuring device from its lowermost sample introduction position to its uppermost sample inspection position through its sleeve housing bottom surface. The measuring device preferably comprises a single electric motor with a mechanical arrangement for actuating the built-in liquid reagent dispensing arrangement of the measuring device and raising its sample slide. Alternatively, the measuring device may include an electromechanical component, such as a small motor, a solenoid and the like, for actuating the built-in liquid reagent dispensing arrangement of the measuring device and raising its sample slide. The measuring device preferably comprises one or more micro switches for ensuring that the newly inserted measuring device is correctly inserted into its tray recess. The measuring device preferably comprises a used measuring device detector for detecting the previously used measuring device to reject the previously used measuring device.

[0009] The measuring device preferably includes two or more optical paths with different magnifications as follows: a first optical path with no magnification, and a second optical path with a magnification of X10 to X1000. The first optical path can be used to acquire low-resolution images, such as target images, pH reading images, and the like. The second optical path can be used to acquire high-resolution microscope images of a body sample, such as along a preferably linear scanning path. The measuring device preferably includes focusing along the second optical path for accurately focusing on the body sample. The measuring device can initially acquire images along the first optical path and subsequently along the second optical path, or vice versa. Alternatively, the measuring device can acquire images along the first optical path and the second optical path simultaneously.

[0010] The measuring device may include two digital image cameras for acquiring the first optical path image and the second optical path image. Alternatively, the measuring device may preferably include a single digital image camera for acquiring the first optical path image and the second optical path image. In the latter case, the measuring device necessarily needs a dual optical path structure with a shutter arrangement, the shutter arrangement being used to selectively open and close the first optical path for acquiring the first optical path image and correspondingly close and open the second optical path for acquiring the second optical path image, so that the single digital image camera acquires the first optical path image when the first optical path is opened and the second optical path is closed, and acquires the second optical path image when the first optical path is closed and the second optical path is opened.

[0011] The one or more digital image cameras may operate under different EMR spectra, particularly including the visible spectrum, IR spectrum, UV spectrum and the like. Thus, the assay device may include different illumination sources for illuminating the assay device under different predetermined EMR spectra. The illumination sources may illuminate the assay device from different directions. The illumination sources may be associated with one or more specific optical paths. For example, some digital images of pH readings must be color images in the visible spectrum. Some microscope images are also preferably color images in the visible spectrum. Microscope images and / or video scans of the body sample are preferably acquired at 30 to 60 frames per second (FPS) to avoid camera blur at lower rates during motion or when the assay device is moved slowly within the assay device. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] In order to understand the invention and to see how it may be carried out in practice, a preferred embodiment will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which like parts are indicated by like numerals, and in which:

[0013] FIG. 1 corresponds to WO 2018 / 235073 A1 Fig.11 ;

[0014] FIG. 2 corresponds to WO 2018 / 235073 A1 Fig.12 ;

[0015] FIG3 corresponds to FIG18 of WO 2018 / 235073 A1;

[0016] FIG. 4 corresponds to FIG. 19 of WO 2018 / 235073 A1;

[0017] Figure 5 is a diagrammatic view of an assay system including an assay device and a handheld assay apparatus having a preassembled handheld sample collection tool;

[0018] Figure 6 is a top perspective view of a handheld assay device having a built-in liquid reagent dispensing arrangement;

[0019] Figure 7 yes Figure 6 A bottom perspective view of the measuring device;

[0020] Figure 8 A hand-held sample collection tool is shown for clamping to Figure 6 Close-up view of the manually operated clamping arrangement of the assay device;

[0021] Fig. 9 yes Figure 6 an exploded view of the assay device;

[0022] Fig.10 yes Figure 6 Left side elevation view of the measuring device;

[0023] Fig.11 yes Figure 6 A right side elevation view of the measuring device;

[0024] Fig.12 yes Figure 6 a bottom perspective view of a cover of the measuring device;

[0025] Fig.13 yes Figure 6 A bottom perspective view of a sample slide of an assay device;

[0026] Fig.14A Before dispensing of liquid reagents Figure 6 A top plan view of the measuring device;

[0027] Fig. 14B During the dispensing of liquid reagents Figure 6 A top plan view of the measuring device;

[0028] Fig.15A is a slide with its sample along Figure 6Line AA in is at its initial lowermost sample introduction position Figure 6 Longitudinal section of the measuring device;

[0029] Fig. 15B is a slide with its sample along Figure 6 Line AA in is in its final uppermost sample inspection position Figure 6 Longitudinal section of the measuring device;

[0030] Fig.16A is a right top perspective view of a handheld assay device having a built-in liquid reagent dispensing arrangement including a stopcock;

[0031] Fig. 16B is a left top perspective view of the measuring device of FIG16;

[0032] Fig.17A is a schematic diagram of the right stopcock of the assay device of FIG. 16 prior to being actuated by its stopcock actuator;

[0033] Fig. 17B is a schematic diagram of a right stopcock after being actuated by its stopcock actuator;

[0034] Fig.18A is a top plan view of the assay device of FIG16 prior to dispensing of the liquid reagent;

[0035] Fig.18B Before dispensing liquid reagents, Fig.18A FIG16 is a transverse cross section of the measuring device at the stepped line BB;

[0036] Fig.19A is a top plan view of the assay device of FIG16 during dispensing of a liquid reagent;

[0037] Fig.19B During the dispensing of liquid reagents Fig.19A FIG16 is a transverse cross section of the measuring device at the stepped line BB;

[0038] Fig. 20 is used with Figure 6 Combined perspective view and block diagram of an assay device used with the assay device;

[0039] Fig.21A yes Fig. 20 Schematic longitudinal section of an assay device along line CC, wherein the complete tray of the assay device is in its outermost position;

[0040] Fig.21B yes Fig. 20 Schematic transverse section of an assay device along line DD, wherein the complete tray of the assay device is in its outermost position;

[0041] Fig.22A yes Fig. 20 Schematic longitudinal section of an assay device along line CC, wherein the complete tray of the assay device is in its innermost position;

[0042] Fig. 22B yes Fig. 20 Schematic transverse section of an assay device along line DD, wherein the complete tray of the assay device is in its innermost position;

[0043] Fig.23 is an exploded view of a tray of the assay assembly;

[0044] Fig.24A is a front perspective view of a tray of an assay assembly wherein an inner tray component of the assay assembly is in its insertion / ejection position relative to an outer tray component thereof;

[0045] Fig. 24B is a front perspective view of a tray of an assay assembly with an inner tray component of the assay assembly in its actuated position relative to an outer tray component thereof;

[0046] Fig.25A is a schematic longitudinal cross-section of an assay system with a complete tray of assay equipment in its outermost position before an assay device is inserted therein;

[0047] Fig.25B is a schematic transverse cross-section of an assay system with a complete tray of assay equipment in its outermost position prior to insertion of an assay device therein;

[0048] Fig.26A is a schematic longitudinal cross-section of an assay system with a complete tray of assay equipment in its outermost position after the assay device has been inserted therein;

[0049] Fig.26B is a schematic transverse cross-section of an assay system with a complete tray of the assay device in its outermost position after the assay device has been inserted therein;

[0050] Fig.27A is a schematic longitudinal cross-section of an assay system illustrating initial inward movement of an outer tray component of the assay device relative to a stationary inner tray component thereof;

[0051] Fig.27B is a schematic transverse cross-section of an assay system illustrating initial inward movement of an outer tray component of the assay device relative to a stationary inner tray component thereof;

[0052] Fig.28A is a schematic longitudinal cross-section of an assay system showing continued inward movement of an outer tray component of the assay device relative to a stationary inner tray component thereof;

[0053] Fig.28B is a schematic transverse cross-section of an assay device illustrating continued inward movement of an outer tray component of the assay device relative to a stationary inner tray component thereof;

[0054] Fig.29A is a schematic longitudinal cross-section of an assay system showing continued inward movement of an outer tray component of the assay device relative to a stationary inner tray component thereof;

[0055] Fig.29B is a schematic transverse cross-section of an assay system illustrating continued inward movement of an outer tray component of the assay device relative to a stationary inner tray component thereof;

[0056] Fig. 30A is a schematic longitudinal section of the assay system showing continued inward movement of the complete tray of assay equipment toward its innermost position;

[0057] Fig. 30B is a schematic transverse cross-section of the assay system showing continued inward movement of the complete tray of assay equipment toward its innermost position;

[0058] Fig.31A is a schematic longitudinal section of the assay system showing continued inward movement of the complete tray of assay equipment toward its innermost position;

[0059] Fig.31B is a schematic transverse cross-section of the assay system showing continued inward movement of the complete tray of assay equipment toward its innermost position;

[0060] Fig.32A is a schematic longitudinal section of the assay system showing continued inward movement of the complete tray of assay equipment toward its innermost position;

[0061] Fig.32B is a schematic transverse cross-section of the assay system showing continued inward movement of the complete tray of assay equipment toward its innermost position;

[0062] Fig.33A is a schematic longitudinal section of an assay system showing a complete tray of assay equipment in its innermost position;

[0063] Fig.33B is a schematic transverse cross-section of an assay system showing a complete tray of assay equipment in its innermost position;

[0064] Fig.34A is a schematic longitudinal section of an assay system showing the outward movement of a complete tray of an assay device until the outward movement of an outer tray component of the assay device relative to a stationary inner tray component thereof begins;

[0065] Fig.34B is a schematic transverse section of an assay system showing outward movement of a complete tray of an assay device until outward movement of an outer tray component of the assay device relative to a stationary inner tray component thereof begins;

[0066] Fig.35A is a schematic longitudinal section of an assay system showing outward movement of an outer tray component of the assay device relative to a stationary inner tray component thereof;

[0067] Fig.35B is a schematic transverse cross-section of an assay system illustrating outward movement of an outer tray component of the assay device relative to a stationary inner tray component thereof;

[0068] Fig.36A is a schematic longitudinal cross-section of an assay system with a complete tray of assay equipment in its outermost position;

[0069] Fig.36B is a schematic transverse cross-section of an assay system with a complete tray of assay equipment in its outermost position;

[0070] Fig.37A is a schematic longitudinal section of an assay system showing an assay device being ejected from a tray recess of an assay apparatus in its outermost position of a complete tray;

[0071] Fig.37B is a schematic transverse cross-section of an assay system showing an assay device being ejected from a tray recess of an assay apparatus in its outermost position of a complete tray;

[0072] Fig.38 is a combined perspective view and block diagram of an assay device for use with the assay apparatus of FIG. 16; and

[0073] Fig.39 is an exploded view of a tray of the illustrated assay assembly for use with the built-in liquid reagent dispensing arrangement of FIG. 16 . DETAILED DESCRIPTION

[0074] WO 2018 / 235073 Assay device and assay equipment used therewith

[0075] Prior art Figures 1 to 4 correspond to the prior art of the commonly owned WO 2018 / 235073 A1 Fig.11 , Fig.12 , Figure 18 and Figure 19. Prior art Figures 1 to 4 show the reference numerals of WO 2018 / 235073.

[0076] 1 and 2 disclose an assay device 10C and a sample handling tool 100. The assay device 10C comprises a box-shaped housing 12 having a housing bottom 16 and a housing top 18. The housing bottom 16 has a transparent housing bottom panel 22. The housing top 18 has a transparent housing top panel 23 aligned with the transparent housing bottom panel 22. The transparent housing top panel 23 comprises sub-panels 23A and 23B. The assay device 10C comprises a sample slide 21 comprising three working surfaces: a leading working surface 51 having a pH detection surface 54 for indicating the pH value of a body sample; a central working surface 52; and a trailing working surface 53. The leading working surface 51, the central working surface 52, and the trailing working surface 53 are spatially discrete to avoid cross contamination.

[0077] The sample handling tool 100 has a leading sample collection end 101, a handle 102, a swab end 103, and a trailing handle 104. The sample handling tool 100 is longer than the box-shaped housing 12, such that the leading swab end 103 of the sample handling tool extends beyond the housing in one direction and the handle 104 of the sample handling tool extends beyond the housing in the opposite direction. The assay device 10C is preferably preassembled with the sample handling tool 100, such that pulling the sample handling tool 100 through the assay device 10C smears the body sample on the three working surfaces 51, 52, and 53, based on obtaining a body sample on the leading swab end 103 of the sample handling tool.

[0078] The assay device 10C includes a manually operated sample slide elevation arrangement 26 for raising the sample slide 21 from its lowermost sample introduction position to its uppermost sample inspection position in which the working surfaces 51, 52 and 53 are juxtaposed against the underside of the housing top panel 23. The assay device 10C includes an integrated liquid reagent pump arrangement 56 having a central liquid reagent reservoir 57 and a tail liquid reagent reservoir 59. Under manual operation of the sample slide elevation arrangement 26, the integrated liquid reagent pump arrangement 56 automatically dispenses liquid reagents from the central liquid reagent reservoir 57 and the tail liquid reagent reservoir 59 onto the body sample on the central working surface 52 and the body sample on the tail working surface 53, respectively.

[0079] The transparent housing bottom panel 22, the transparent housing top panel 23 and the sample slide 21 are transparent under one or more predetermined EMR spectra, particularly including the visible spectrum, the IR spectrum, the UV spectrum and the like. Thus, in the uppermost sample inspection position, the assay device 10C has one inspection line for inspecting the pH detection surface 54 and two inspection lines for inspecting the body sample on the central working surface 52 and the rear working surface 53.

[0080] 3 and 4 disclose an assay device 10D for use with an assay apparatus 200, typically in the form of a digital microscope. The assay device 10D has a longitudinal assay device centerline 34 and a leading auxiliary end surface 38. The assay device 10D includes a pair of liquid reagent injection ports 64 in its housing top surface 18 for manually injecting liquid reagents onto its working surface. The leading auxiliary end surface 38 includes a pair of slots 62 spaced across its width and below the sample slide 21 in its initial lowermost sample introduction position.

[0081] The measuring device 200 includes a measuring device tray 202 that reciprocates between the measuring device access position of Figure 18 of WO 2018 / 235073 and the measuring device inspection position of Figure 21 of WO 2018 / 235073. The measuring device tray 202 includes a sample slide elevation component 203 for sliding insertion through the slot pair 62 into the measuring device 10D along the longitudinal measuring device centerline 34 of the measuring device, so as to push its sample slide 21 from its lowermost sample introduction position to its uppermost sample inspection position after the injection of the liquid reagent. The sample slide elevation component 203 is preferably a fork shape with spaced-apart elevation forks 204 that do not block the inspection line through the measuring device 10D. The measuring device 200 can be a stand-alone device with built-in information collection and diagnostic capabilities for examining body samples. Alternatively, the measuring device 200 can transmit images and other information obtained from the body sample for remote processing.

[0082] Measurement system

[0083] Figure 5 An assay system 10 for diagnostic purposes of a body sample is shown. The assay system 10 comprises a handheld assay device 100 for use in a tabletop assay device 200 suitable for deployment in outpatient clinics and similar locations. The assay device 200 may be powered by mains electricity, rechargeable batteries, and the like. Similar to the aforementioned WO 2018 / 235073 assay device 200, the assay device 200 may be a stand-alone device with built-in diagnostic capabilities for diagnostic purposes and / or may transmit acquired images and other information for remote processing.

[0084] The assay device 100 is preferably preassembled with the sample collection tool 50 for ease of use. The assay device 100 and the sample collection tool 50 preferably include a manually operated clamping arrangement 107 for initially clamping the sample collection tool 50 to the assay device 100 to prevent relative movement between the sample collection tool and the assay device during transport and also during obtaining a body sample. After obtaining a body sample and before inserting the assay device 100 in the assay apparatus 200 for diagnostic purposes, the manually operated clamping arrangement 107 is released to enable sliding removal of the sample collection tool 50 from the assay device 100. Alternatively, the assay device 100 and the sample collection tool 50 may be provided as discrete items.

[0085] The assay device 200 includes an apparatus housing 201 having a tray 202 that reciprocates between an outermost position and an innermost position. The tray 202 has a longitudinal tray centerline 202A and a longitudinal tray recess 203 centrally located along it for interchangeably receiving an assay device 100. The tray 202 includes a manually operated ejection mechanism 204 having an ejection button 204A for ejecting the assay device 100 from the tray recess 203 after the assay device has been processed to obtain diagnostic information. The tray recess 203 preferably includes one or more micro switches 205 for ensuring that the assay device 100 has been correctly inserted. The tray 200 includes a color target 206 for calibration purposes as explained below. The assay device 200 may include a barcode reader for reading a barcode of an assay device to determine that the assay device 100 is an authorized assay device.

[0086] Assay device including sample collection tool

[0087] Figure 6 15 shows an assay device 100 having a longitudinal assay device centerline 101 and comprising a generally box-shaped cartridge housing 102 having a cartridge housing interior 103 snugly accommodating a sample slide 104 that is slidably raised from an initial lowermost sample introduction position to a final uppermost sample examination position. The cartridge housing 102 is preferably formed of a transparent plastic material, such as polycarbonate and the like. The assay device 100 comprises a sample slide securing arrangement 105 for securing the sample slide 104 in its final uppermost sample examination position. The assay device 100 comprises a built-in liquid reagent dispensing arrangement 106 for dispensing a liquid reagent on a body sample applied to the sample slide 104 in its initial lowermost sample introduction position.

[0088] The sleeve housing 102 includes a sleeve housing top surface 108, a sleeve housing bottom surface 109 opposite to the sleeve housing top surface 108, and a sleeve housing outer peripheral surface 111. The sleeve housing outer peripheral surface 111 includes a pair of opposite main side walls 112 and a main side wall 113 in the same direction as the longitudinal measuring device centerline 101, a leading auxiliary end surface 114 transverse to the longitudinal measuring device centerline 101, and a trailing auxiliary end surface 116 transverse to the longitudinal measuring device centerline 101 and opposite to the leading auxiliary end surface 114. For explanatory purposes, from the point of view of providing a view of the leading auxiliary end surface 114, the main side wall 112 is hereinafter referred to as the main right side wall and the main side wall 113 is hereinafter referred to as the main left side wall. From the point of view of providing a view of the leading auxiliary end surface 114, additional parts are similarly referred to as right and left below.

[0089] The leading auxiliary end surface 114 has a leading through hole 117 and the trailing auxiliary end surface 116 has a trailing through hole 118, both of which are disposed along the longitudinal measuring device centerline 101 to allow the sample collection tool 50 to pass therethrough. The sleeve housing top surface 108 includes a pair of spaced-apart cutouts 119 adjacent to the trailing auxiliary end surface 116 on both sides of the longitudinal measuring device centerline 101. The trailing auxiliary end surface 116 includes a pair of spaced-apart trailing blind holes 121 on both sides of the trailing through hole 118.

[0090] The sample collection tool 50 comprises an elongated shaft 51 having a leading sample collection tip 52 in the form of a brush, swab and the like, and a trailing end 53. The trailing end 53 comprises a semi-elliptical planar handle 54 having a pair of spaced longitudinal slits 56 in the same direction as the shaft 51 for forming a manually depressible release button 57 flexibly connected to a handle surround 58. The release button 57 comprises a pair of spaced leading clips 59 for snap-fitting into a pair of spaced notches 119 of the assay device in the assembled state of the assay device 100 and the sample collection tool 50. The handle surround 58 comprises a pair of spaced circular protrusions 61 for insertion into a pair of spaced trailing blind holes 121 of the assay device in the assembled state of the assay device 100 and the sample collection tool 50.

[0091] Figure 5 The assay device 100 is shown to include a protective foil 122 covering the cartridge housing top surface 108 and the leading auxiliary end surface 114. The protective foil 122 remains in place during the acquisition of a body sample and is removed prior to insertion of the assay device 100 into the assay apparatus 200 for diagnostic purposes. The protective foil 122 prevents fingerprints on the cartridge housing top surface 108, which could degrade the imaging of the assay apparatus 200. The protective foil 122 ensures that the leading auxiliary end surface 114 remains free of any body sample that might otherwise remain when the sample collection tool 50 is slidably removed from the assay device 100 and result in contamination of the interior of the assay apparatus 200.

[0092] The cartridge housing 102 comprises a two-component construction: a base 123 and a cover 124 for mounting on the base 123. The base 123 comprises a cartridge housing bottom surface 109, a tail auxiliary end surface 116, and a tail section of the cartridge housing top surface 108 having a pair of spaced-apart cutouts 119. The cartridge housing 109 is formed with a leading through hole 126 and a tail through hole 127, both of which are disposed along the longitudinal assay device centerline 101 for providing access to the cartridge housing interior 103. The base 123 comprises a pair of opposing main right side walls 128 and main left side walls 129 transverse to the longitudinal assay device centerline 101, which are respectively formed with a longitudinal right barrel 131 and a longitudinal left barrel 132 of the built-in liquid reagent dispensing arrangement 106.

[0093] The cover 124 includes a sleeve housing top surface 108 and a leading auxiliary end surface 114. The leading auxiliary end surface 114 is formed with a pair of spaced leading through holes 133 and 134, which are aligned with a pair of spaced longitudinal right barrels 131 and longitudinal left barrels 132. The sleeve housing top surface 108 includes a longitudinal arrangement of three panels transparent to a predetermined EMR spectrum. The three panels include a generally square leading sleeve housing top surface panel 136 adjacent to the leading auxiliary end surface 114, a generally rectangular intermediate sleeve housing top surface panel 137 midway between the leading auxiliary end surface 114 and the tail auxiliary end surface 116, and a generally rectangular tail sleeve housing top surface panel 138 adjacent to the tail auxiliary end surface 116. The intermediate sleeve housing top surface panel 137 overlies the leading through hole 126. The tail sleeve housing top surface panel 138 overlies the tail through hole 127. Alternatively, the leading quill case top surface panel 136, the intermediate quill case top surface panel 137, and the trailing quill case top surface panel 138 may be formed as a single panel.

[0094] The cartridge housing top surface 108 includes a pair of spaced arrows 139 toward the leading auxiliary end surface 114 , which point in the direction of the leading auxiliary end surface 114 for assisting a user in correctly placing an unused assay device 100 in the assay apparatus 200 . Fig.12 The cartridge housing top surface 108 is shown to include a leading guide member 141 and a trailing guide member 142 depending downwardly into the cartridge housing interior 103 for guiding the handheld sample collection tool 50 to be slid out of the assay device 100 for applying a body sample on the sample slide 104. The leading guide member 141 and the trailing guide member 142 respectively have central apertures 141A and 142A along the longitudinal assay device centerline 101 for the handheld sample collection tool 50 to pass therethrough.

[0095] The sample carrier 104 has three spatially discrete working surfaces along the longitudinal assay device centerline 101, as follows: a leading working surface 143 having a pH detection surface 144 for indicating the pH value of a body sample, a central working surface 146, and a trailing working surface 147. The pH detection surface 144 may be litmus paper or other pH sensitive material. The central working surface 146 has a generally rectangular sample carrier panel 148 oriented longitudinally along the longitudinal assay device centerline 101 and a target 148A toward its front end. The trailing working surface 147 has a generally rectangular sample carrier panel 151 oriented longitudinally along the longitudinal assay device centerline 101 and a target 151A toward its front end. The leading working surface 143 is aligned with the leading sleeve housing top panel 136, the sample carrier panel 148 and the target 148A are aligned with the intermediate sleeve housing top panel 137, and the sample carrier panel 151 and the focal target 151A are aligned with the trailing sleeve housing top panel 138. Sample carrier panel 148 and sample carrier panel 151 are transparent to the same EMR wavelengths as intermediate sleeve housing top panel 137 and aft sleeve housing top panel 138 .

[0096] A pair of opposite longitudinal right barrels 131 and left barrels 132 are associated with the central working surface 146 and the tail working surface 147 of the sample slide, respectively. The right barrel 131 and the left barrel 132 have similar constructions and their corresponding components are indicated as A and B. The right barrel 131 and the left barrel 132 include leading seals 152A and 152B facing the leading auxiliary end face 114. The leading seals 152A and 152B are exposed through the leading through holes 133 and 134. The right barrel 131 and the left barrel 132 include tail sealing components 153A and 153B facing the tail auxiliary end face 116. The right barrel 131 and the left barrel 132 contain liquid reagents 154A and 154B. The leading seal 152 and the tail sealing component 153 are preferably visually distinguishable in the sleeve housing 102 to determine whether the assay device has been used as described below with reference to the assay device 200. The right barrel 131 and the left barrel 132 have liquid reagent dispensing ports 156A and 156B midway along the central working surface 146 and the rear working surface 147 , respectively, for dispensing the liquid reagents 154A and 154B on the working surfaces.

[0097] Fig.14A The assay device 100 is shown in an initial pre-liquid reagent dispensing position in which its leading seals 152A and 152B are positioned adjacent to the leading auxiliary end surface 114, and its trailing seal components 153A and 153B are positioned adjacent to and forward of their respective liquid reagent dispensing ports 156A and 156B relative to the leading auxiliary end surface 114. Fig.14AThe plungers 157A and 157B of the assay assembly 200 are also shown to be inserted into the right barrel 131 and the left barrel 132 .

[0098] Fig. 14B The sliding insertion of the plunger 157A into the right barrel 131 is shown to push the leading seal 152A, the liquid reagent 154A and the trailing seal component 153A along the right barrel 131 until the trailing seal component 153A passes through the liquid reagent dispensing port 156A, thereby enabling the liquid reagent 154A to be dispensed onto the central working surface 146 and the sample carrier panel 148 through the liquid reagent dispensing port 156A.

[0099] Fig. 14B Similarly shown, sliding insertion of the plunger 157B into the left barrel 132 pushes the leading seal 152B, liquid reagent 154B and tail seal component 153B along the left barrel 132 until the tail seal component 153B passes through the liquid reagent dispensing port 156B, thereby enabling the liquid reagent 154B to be dispensed onto the tail working surface 147 and the sample carrier panel 151 through the liquid reagent dispensing port 156B.

[0100] Fig. 14B The assay device 100 is shown near the end of dispensing liquid reagents 154A and 154B, as evidenced by the almost empty right barrel 131 and left barrel 132. Depending on the length of the plungers 157A and 157B inserted into the right barrel 131 and left barrel 132, the leading seals 152A and 152B may also be pushed through the liquid reagent dispensing ports 156A and 156B.

[0101] The sample slide 104 includes a central longitudinally oriented elongated elevation support 158 ​​and a trailing longitudinally oriented elongated elevation support 159, which depend downwardly from the central working surface 146 and the trailing working surface 147, respectively, and are aligned with the leading through hole 126 and the trailing through hole 127, respectively. The central elevation support 158 ​​and the trailing elevation support 159 are lateral to the longitudinal assay device centerline 101 so as not to obstruct EMR transmission through the assay device 100 and scanning along the sample slide panel 148 and the sample slide panel 151.

[0102] The center elevation support 158 ​​and the tail elevation support 159 are pushed upward by the leading elevation member 161 and the tail elevation member 162 of the assay assembly 200 for use in moving the sample slide 104 from its lowermost sample introduction position (see Fig.15A ) to its uppermost specimen inspection position (see Fig. 15B). The sample carrier 104 is respectively away from and adjacent to the sleeve housing top surface 108 in the initial lowermost sample introduction position and the final uppermost sample inspection position. In the final uppermost sample inspection position, the body sample reacting with the liquid reagent 154A on the central working surface 146 is compressed against the lower side of the middle sleeve housing top surface panel 137, and the body sample reacting with the liquid reagent 154B on the rear working surface 147 is compressed against the lower side of the rear sleeve housing top surface panel 138.

[0103] The sample slide securing arrangement 105 for securing the sample slide 104 in its final uppermost sample examination position preferably effects an irreversible single displacement from the initial lowermost sample introduction position to the final uppermost sample examination position to prevent reuse of the assay device 100 . Fig. 9 1. An embodiment of the sample slide securing arrangement 105 is best seen in FIG. 1: the major right side wall 128 of the base 123 has a spaced pair of inwardly directed protrusions 163 (obstructed from view), and the major left side wall 129 thereof has a spaced pair of inwardly directed protrusions 164 opposite the spaced pair of inwardly directed protrusions 163. The sample slide 104 has a spaced pair of outwardly biased clips 166 aligned with the spaced pair of inwardly directed protrusions 163. The sample slide 104 has a spaced pair of outwardly biased clips 167 aligned with the spaced pair of inwardly directed protrusions 164 (obstructed from view). As the sample carrier 104 is displaced upward from its initial lowermost sample introduction position to its final uppermost sample inspection position, a pair of spaced-apart outwardly biased clips 166 irreversibly pass through a pair of spaced-apart inwardly directed protrusions 163, and a pair of spaced-apart outwardly biased clips 167 irreversibly pass through a pair of spaced-apart inwardly directed protrusions 164.

[0104] The assay device 100 may be provided with an alternative built-in liquid reagent dispensing arrangement 106', wherein the right barrel 131 cooperates with the right stopcock 168A and the left barrel 132 cooperates with the left stopcock 168B. The right stopcock 168A and the left stopcock 168B act as tail sealing components. The construction of the latter arrangement 106' is largely similar to the previous arrangement 106, and therefore similar parts are similarly numbered.

[0105] FIG. 16A to FIG. 19BThe right barrel 131 and the left barrel 132 are shown to receive the cocks 168A and 168B in a rotational manner at their liquid reagent dispensing ports 156A and 156B. The right cock 168A and the left cock 168B are permanently disposed at their corresponding liquid reagent dispensing ports 156A and 156B. The right barrel 131 and the left barrel 132 are respectively formed with cock grooves 169A and 169B relative to their liquid reagent dispensing ports 156A and 156B. The cocks 168A and 168B have cock actuation tabs 171A and 171B (see Fig.18B and Fig.19B The assay assembly 200 includes right stopcock actuators 190A and left stopcock actuators 190B for rotating right stopcocks 168A and left stopcocks 168B from an initial closed position in a pre-liquid reagent dispensing position to an open position for liquid reagent dispensing purposes upon forward displacement thereof toward right stopcocks 168A and left stopcocks 168B, respectively.

[0106] Fig.16A The right tap 168A is shown rotated approximately 45° counterclockwise from its initial closed position to its open position as evidenced by the position of its tap actuation tab 171A changing from its closed position shown in solid lines to its open position shown in phantom lines. Fig. 16B The left tap 168B is similarly shown rotated approximately 45° clockwise from its initial closed position to its open position as evidenced by the position of its tap actuation tab 171B changing from its closed position shown in solid lines to its open position shown in phantom lines.

[0107] Fig.17A and Fig. 17B The right stopcock 168A is shown to have a cylindrical body 172 with a rotation axis 173 coaxial with the right barrel 131, the cylindrical body having a leading stopcock face 174 facing the leading auxiliary end face 114, a trailing stopcock face 176 facing away from the leading auxiliary end face 114, and a peripheral stopcock face 177 extending between the leading stopcock face 174 and the trailing stopcock face 176. The right stopcock 168A includes an L-shaped channel 178A extending from its front stopcock face 174A to its peripheral stopcock face 177A. The L-shaped channel 178A has an L-shaped channel inlet 179A in the front stopcock face 174A that is in flow communication with the right barrel 131 and an L-shaped channel outlet 181A in the peripheral stopcock face 177A for selective flow communication with the liquid reagent dispensing port 156A.

[0108] Fig.17A and Fig. 17BThe right stopcock actuator 190A is shown with a leading stopcock actuator taper 191A facing the stopcock actuation tab 171A. The leading stopcock actuator taper 191A gradually narrows from the frontmost innermost tip 192A to the rearmost outermost edge 193A. The stopcock actuator 190A initially contacts the stopcock actuation tab 171A at its frontmost innermost tip 192A. During the subsequent approach of the stopcock actuator 190A and the right stopcock 168A as indicated by arrow A, when the leading stopcock actuator taper 191A moves below the right stopcock actuation tab 171A, the stopcock actuator 190A gradually rotates the right stopcock 168A counterclockwise to its liquid reagent dispensing position as indicated by arrow B.

[0109] The left stopcock 168B is a mirror image of the right stopcock 168A relative to the longitudinal measuring device centerline 101. Similarly, the left stopcock actuator 190B is a mirror image of the right stopcock actuator 190A relative to the longitudinal measuring device centerline 101.

[0110] Fig.18A and Fig.18B The right and left stopcocks 168A, 168B are shown in their initial pre-liquid reagent dispensing positions with their stopcock actuation tabs 171A, 171B directed downwardly adjacent to the major right and left side walls 112, 113 and their L-shaped channel outlets 181A, 181B sealed against the inner surfaces of their respective barrels 131, 132. The plungers 157A, 157B of the assay assembly 200 are to be inserted into the right and left barrels 131, 132. The right and left stopcock actuators 190A, 190B are in front of the right and left stopcocks 168A, 168B, respectively.

[0111] Fig.19A and Fig.19B The plungers 157A and 157B inserted into the right barrel 131 and the left barrel 132 are shown, and the right and left stopcock actuators 190A and 190B have respectively rotated the right and left stopcocks 168A and 168B to their liquid reagent dispensing positions, as evidenced by their stopcock actuation tabs 171A and 171B protruding outward relative to their respective main right side wall 112 and main left side wall 113. The L-shaped channel outlets 181A and 181B are aligned with their respective liquid reagent dispensing ports 156A and 156B. The liquid reagent dispensing arrangement 106' dispenses the liquid reagent 154A onto the sample slide panel 148 through the liquid reagent dispensing port 156A, and dispenses the liquid reagent 154B onto the sample slide panel 151 through the liquid reagent dispensing port 156B.

[0112] Measurement equipment

[0113] Reference now Fig. 2024 an assay apparatus 200 for use with an assay device 100 having a built-in liquid reagent dispensing arrangement 106 is described. Fig.21A and Fig.22A is a schematic longitudinal cross-section of the assay device 200 that has been modified to show components that would not otherwise be shown in the longitudinal cross-section along the longitudinal section line CC. Fig.21A and Fig.22A Included along Fig.23 An assembly of the stepped longitudinal section line EE is shown. Fig.21B and Fig. 22B is a schematic transverse cross-section of an assay device 200 that has been modified to show components that would not otherwise be shown in the transverse cross-section along transverse cross-section line DD.

[0114] As mentioned above Figure 5 As depicted, the assay device 200 includes a device housing 201 having a tray 202 having a longitudinal tray centerline 202A and at an outermost position (see Fig.21A and Fig.21B ) and the innermost position (see Fig.22A and Fig. 22B ). The tray 202 includes a tray recess 203 for interchangeably receiving the assay device 100 so that its longitudinal assay device centerline 101 is oriented in the same direction as the longitudinal tray centerline 202A. The tray 202 includes a manually operated ejection mechanism 204, which includes an ejection button 204A for ejecting the assay device 100 after the assay device has been processed to obtain diagnostic information. The tray 202 has a color target 206 for calibration purposes for accurately determining the pH color reading of the assay device 100. The assay apparatus 200 stops the tray 202 in its outermost position in the event that the assay device 100 has been incorrectly inserted, and issues an audible or visual warning for alerting the user.

[0115] The measuring device 200 includes a controller 207 for controlling its operation, a user interface 208 for inputting information about the clinical procedure, and a start button 209. The measuring device 200 includes a motor arrangement 211 having a motor 212 for driving a helical threaded drive shaft 213 to reciprocate the tray 202 between its outermost position and its innermost position. Clockwise rotation of the drive shaft 213 pushes the tray 202 from its outermost position to its innermost position, and conversely, counterclockwise rotation of the drive shaft 213 pushes the tray 202 from its innermost position to its outermost position.

[0116] The measuring device 200 comprises a digital color acquisition arrangement 214 with a single color camera 216 having an optical axis 217 and a dual optical path as follows: a first optical path 218 (see Fig.21A), which is used to obtain a color target image of the color target 206 of the tray 202 and a color pH reading image of the pH detection surface 144 of the measuring device. And a second optical path 219 (see Fig.22A ), which is used to obtain a microscope image of the body sample from the central working surface 146 and the rear working surface 147 of the assay device after reacting with the liquid reagent 154A and the liquid reagent 154B, respectively. The color camera 216 is, for example, any commercially available 4 to 25 megapixel CMOS image sensor. The assay device 200 preferably acquires a color target image, a color pH reading image, and a microscope image of the assay device 100 during a single continuous inward movement of the tray 202 from its outermost position to its innermost position.

[0117] The digital color acquisition arrangement 214 includes two mirrors along the optical axis 217 and tilted at 45° thereto, as follows: a half-reflective mirror 221 close to the color camera 216, and a full-reflective mirror 222 away from the color camera 216. Thus, the first optical path 218 includes the half-reflective mirror 221 and the full-reflective mirror 222. The digital color acquisition arrangement 214 includes a X10 to X1000 magnification lens system 224 for acquiring microscope images. Thus, the second optical path 219 includes the half-reflective mirror 221 and the X10 to X1000 magnification lens system 224. The digital color acquisition arrangement 214 also preferably includes an autofocus capability along the second optical path 219.

[0118] For use during image acquisition along the first optical pathway 218, the digital color acquisition arrangement 214 includes a first illumination source 226 disposed above the tray 202 for illuminating the assay device 100 from above, and a first optical pathway shutter 227 for selectively opening and closing the first optical pathway 218. For use during image acquisition along the second optical pathway 219, the digital color acquisition arrangement 214 includes a second illumination source 228 disposed below the tray 202 for backlighting the assay device 100 through the tray 202, and a second optical pathway shutter 229 extending inwardly from the tray 202 for selectively opening and closing the second optical pathway 219. The first optical pathway shutter 227 and the second optical pathway shutter 229 work in unison to constitute a shutter arrangement 231 for selectively opening and closing the first optical pathway 218 and correspondingly closing and opening the second optical pathway 219. Therefore, the digital color acquisition arrangement 214 acquires the color target image and the pH reading image by turning on only the illumination source 226, opening the first optical path 218, and closing the second optical path 219. And the digital color acquisition arrangement 214 acquires the microscope image by turning on only the illumination source 228, closing the first optical path 218, and opening the second optical path 219.

[0119] Fig.23Figures 24 show that the tray 202 includes the following components: an outer tray member 232 having a tray recess 203 and an ejection button 204A. An inner tray member 233 reciprocates longitudinally slidably within the outer tray member 232 between a measurement device insertion / ejection position of the measurement device 100 in the tray recess 203 (see Fig.24A ) and an actuated measurement device position of the measurement device 100 in the tray recess 203 (see Fig. 24B ). And a restraint mechanism 234 for selectively restraining the movement of the inner tray member 233 relative to the outer tray member 232. When the restraint mechanism 234 is enabled, the inner tray member 233 can be displaced between its measurement device insertion / ejection position and its measurement device actuation position. When the restraint mechanism 234 is disabled, the inner tray member 233 is coupled to the outer tray member 232 such that, as driven by the drive shaft rod 213, the inner tray member 233 moves in series with the outer tray member 232.

[0120] The outer tray member 232 has opposing longitudinal surfaces 236, each having a leading auxiliary cam surface 237 inclined relative to the longitudinal tray centerline 202A and a trailing main surface 238 parallel thereto. The restraint mechanism 234 consists of a pair of opposing restraint members 239 that act against the opposing longitudinal surfaces 236. The restraint members 239 are preferably spring-biased by a pair of compression springs 241 that have an uncompressed length L1 (see Fig.21B ) in the enabled state of the restraint mechanism 234 for restraining the movement of the inner tray member 233 relative to the outer tray member 233, and a fully compressed length L2 < L1 (see Fig. 22B ) in the disabled state of the restraint mechanism 234 for enabling the inner tray member 233 to move in series with the outer tray member 232.

[0121] The outer tray member 232 includes a main outer tray member assembly 242 and an auxiliary outer tray member assembly 243 fixedly mounted on the main outer tray member assembly 242. The main outer tray member assembly 242 is fixedly mounted on the drive shaft rod 213. The auxiliary outer tray member assembly 243 includes the tray recess 203. The inner tray member 233 reciprocates longitudinally slidably between the main outer tray member assembly 242 and the auxiliary outer tray member assembly 243.

[0122] The main outer tray member assembly 242 has an empty interior for implementing backlighting of the measurement device 100. The main outer tray member assembly 242 includes a longitudinal leading compartment 244 that houses a leading sample slide elevation member 246 and a longitudinal trailing compartment 247 that houses a trailing sample slide elevation member 248. The leading sample slide elevation member 246 and the trailing sample slide elevation member 248 were previously described as Fig.15Aand Fig. 15B 1 and 16. The leading sample carrier elevation component 161 and the sample carrier tail elevation component 162 are shown in FIG. The leading sample carrier elevation component 246 and the tail sample carrier elevation component 248 are preferably spring biased, but may alternatively be displaced by electromechanical components such as small motors, solenoids, and the like. The leading sample carrier elevation component 246 has a top leading sample carrier elevation component surface 249 having a horizontal leading surface 249A and an inclined tail surface 249B. The tail sample carrier elevation component 248 has a top tail sample carrier elevation component surface 251 having a horizontal leading surface 251A and an inclined tail surface 251B.

[0123] Compartments 244 and 247 are on opposite sides of the longitudinal tray centerline 202A, thereby leaving the longitudinal tray centerline 202A unobstructed for scanning along it. A leading sample carrier elevation component 246 is deployed for pushing the center elevation support 158 ​​of the assay device. A trailing sample carrier elevation component 248 is deployed for pushing the trailing elevation support 159 of the assay device. The leading sample carrier elevation component 246 and the trailing sample carrier elevation component 248 together push the sample carrier 104 of the assay device from its initial lowermost sample introduction position to its final uppermost sample inspection position. The leading sample carrier elevation component 246 and the trailing sample carrier elevation component 248 also couple the inner tray component 233 to the outer tray component 232 so that the inner tray component 233 moves in series with the outer tray component 232 as driven by the drive shaft 213.

[0124] The inner tray component 233 has a generally L-shaped configuration including a leading head member 252 and a trailing elongated plate 253. The leading head member 252 includes a color target 206 and a second optical path shutter 229 extending inwardly toward the second optical path 219. The head member 252 includes a right plunger 254 and a left plunger 256 in the direction of the trailing elongated plate 253 for sliding insertion into the right barrel 131 and the left barrel 132 of the assay device, respectively, for dispensing liquid reagent therefrom to react with a body sample in the assay device actuation position of the inner tray component 233. The plungers 254 and 256 were previously described as Fig.14A and Fig. 14B Plunger 157A and 157B are shown.

[0125] The trailing elongated plate 253 includes a longitudinal elongated main slot 257 along the longitudinal tray centerline 202A for enabling backlighting therethrough for scanning purposes along the second optical path 219. The trailing elongated plate 253 includes a longitudinal leading slot 258 associated with the leading sample carrier elevation component 246 and a longitudinal trailing slot 259 associated with the trailing sample carrier elevation component 248. In the assay device insertion / ejection position of the inner tray component, the leading sample carrier elevation component 246 and the trailing sample carrier elevation component 248 are in a blocking position below the plate 253. In the assay device actuation position of the inner tray component, the leading sample carrier elevation component 246 and the trailing sample carrier elevation component 248 exit through the leading slot 258 and the trailing slot 259, respectively.

[0126] Upon sliding displacement of the inner tray component 233 relative to the outer tray component 232 from its assay device insertion / ejection position to its assay device actuated position, the angled tail surface 249B acts against the plate 253 to enable the leading sample carrier elevation component 246 to gradually withdraw through the leading slot 258. More importantly, upon sliding displacement of the inner tray component 233 relative to the outer tray component 232 from its actuated assay device position to its assay device insertion / ejection position, the angled tail surface 249B acts against the plate 253 for gradually pressing the leading sample carrier elevation component 246 to enable it to gradually travel under the plate 253 to its blocking position in the assay device insertion / ejection position of the inner tray component 233.

[0127] Similarly upon sliding displacement of the inner tray component 233 relative to the outer tray component 232 from its assay device insertion / ejection position to its assay device actuated position, the inclined tail surface 251B acts against the plate 253 to enable the trailing specimen carrier elevation component 248 to gradually withdraw through the trailing slot 259. More importantly, upon sliding displacement of the inner tray component 233 relative to the outer tray component 232 from its actuated assay device position to its assay device insertion / ejection position, the inclined tail surface 251B acts against the plate 253 for gradually depressing the trailing specimen carrier elevation component 248 to enable it to gradually travel beneath the plate 253 to its blocking position in the assay device insertion / ejection position of the inner tray component 233.

[0128] The measuring device 200 preferably includes a used measuring device detector 261, which is used to determine whether the measuring device newly inserted in the tray recess 203 is an unused measuring device before the operation of the measuring device 200 for obtaining diagnostic information. Such detection preferably involves determining whether the built-in liquid reagent distribution arrangement of the newly inserted measuring device has been previously actuated. Such detection preferably compares one or more parameters of the newly inserted measuring device with the reference parameters for the unused measuring device. One such reference parameter is the electric motor power consumption of the leading seal of the initial displacement measuring device, because such displacement needs to overcome friction to push the seal along the barrel. The unused measuring device requires a larger electric motor power consumption than the used measuring device. Another method is to optically detect the position of the leading seal and / or the tail seal of the newly inserted measuring device. The leading seal and / or the tail seal of the used measuring device are farther along the barrel than the leading seal and / or the tail seal of the unused measuring device.

[0129] The assay device 200 preferably includes a UV light source 262 for killing bacteria within the device housing 201 .

[0130] Use of the measurement system

[0131] The use of the assay system 10 for acquiring diagnostic information from an assay device 100 will now be described with reference to Figures 25 to 37. Figures 25 to 37 show a complete cycle of operation of the assay device 200 from the insertion of a new assay device 100 to the ejection of the spent assay device 100 after the diagnostic information has been acquired therefrom. After ejecting the spent assay device 100, the assay device 200 is fully reset for the insertion of a new assay device 100.

[0132] FIG. 25A to FIG. 37A is similar to Fig.21A and Fig.22A , and is similarly modified to show components that would not otherwise be shown in the longitudinal section along the longitudinal section line BB. FIG. 25B to FIG. 37B is similar to Fig.21B and Fig. 22B , and is similarly modified to show components that would not otherwise be shown in the transverse section along transverse section line CC.

[0133] Fig.25A and Fig.25BAn assay system 10 is shown with an assay device 200 whose tray 202 is in its outermost position ready for insertion of a new assay device 100 in its tray recess 203. The assay device 100 is suitably prepared by initially sliding its sample collection tool 50 through it for smearing a body sample on its sample slide 104, and subsequently removing its protective foil 122. The user enters information about the current clinical procedure, such as patient details etc. on the user interface 208. The patient details comprise inter alia name, ID number and age.

[0134] In the outermost position of the tray 202, the assay apparatus 200 is arranged as follows: the inner tray component 233 is in its assay device insertion / ejection position relative to the outer tray component 232. The inner tray component 233 blocks the leading sample carrier elevation component 246 and the trailing sample carrier elevation component 248. The color target 206 of the tray is positioned along the first optical path 218. The first optical path shutter 227 is open. The second optical path shutter 229 of the tray closes the second optical path 219. As evidenced by the compression spring being at its fully uncompressed length L1, the restraining mechanism 234 is activated for restraining movement of the inner tray component 233 relative to the outer tray component 232, so that the outer tray component 232 can be displaced inwardly while the inner tray component 233 remains stationary.

[0135] Fig.26A and Fig.26B The assay device 100 is shown snugly inserted into the tray recess 203 and activating the micro switch 205 if correctly inserted. The user presses the start button 209 and the assay device 200 checks that the assay device 100 has been correctly inserted into the tray recess 203 and stops operation if the assay device 100 is incorrectly inserted. If the assay device 100 has been incorrectly inserted, the assay device 200 warns the user. The used assay device detector 261 checks that the assay device 100 is unused and issues a warning if the assay device 100 is a previously used assay device. The controller 207 turns on the illumination source 226 for illuminating the color target 206 of the tray and the digital color camera 216 acquires an image of the color target along the first optical path 218. The illumination source 226 remains on until after the digital color camera 216 acquires the color pH reading image.

[0136] Fig.27A and Fig.27BThe initial inward movement of the outer tray component 232 relative to the stationary inner tray component 233 is shown, which results in the following simultaneous actions: the plungers 254 and 256 enter the barrels 131 and 132 respectively for dispensing liquid reagent 154A on the central working surface 146 and liquid reagent 154B on the trailing working surface 147. The leading elevation component 246 approaches the slot 258. The trailing elevation component 248 approaches the slot 259. The compression spring 241 begins to compress.

[0137] Fig.28A and Fig.28B The outer tray member 232 is shown continuing to move inwardly relative to the stationary inner tray member 233, which results in the following simultaneous actions: the plungers 254 and 256 continue to dispense the liquid reagent 154A and the liquid reagent 154B. The leading sample slide elevation member 246 begins to withdraw upwardly through the leading slot 258 into the tray well 203. The trailing sample slide elevation member 248 begins to withdraw upwardly through the trailing slot 259 into the tray well 203. The compression spring 241 is further compressed to deactivate the restraining mechanism 234.

[0138] Fig.29A and Fig.29B The continued inward movement of the outer tray component 232 relative to the stationary inner tray component 233 is shown to the moment immediately before the restraining mechanism 234 is deactivated, as evidenced by the compression of the compression spring 241 to its fully compressed length L2. The deactivation of the restraining mechanism 234 enables the inner tray component 233 to be coupled to the outer tray component 232 for continued inward movement of the complete tray 202, i.e., both the outer tray component 232 and the inner tray component 233 in series. The inner tray component 233 is in its actuated assay device position relative to the outer tray component 232 as long as the leading sample slide elevation component 246 is further withdrawn upward through the leading slot 258 and the trailing sample slide elevation component 248 is further withdrawn upward through the trailing slot 259 into the tray pocket 203 to latch the inner tray component 233 to the outer tray component 232 for continued inward movement thereof in combination and to push the sample slide 104 of the assay device upward toward its final uppermost sample inspection position.

[0139] Fig. 30A and Fig. 30B Continued inward movement of the complete tray 202 is shown, causing the leading sample carrier elevation component 246 to fully withdraw through the leading narrow slot 258 and the trailing sample carrier elevation component 248 to fully withdraw through the trailing narrow slot 259 into the tray recess 203 to push the sample carrier 104 of the assay device fully upward into its final uppermost sample inspection position.

[0140] Fig.31A and Fig.31BThe full tray 202 is shown continuing to move inwardly until the pH sensing surface 144 of the assay device 100 is positioned along the first optical pathway 218. The digital color camera 216 acquires a color pH reading image. The controller 207 turns off the illumination source 226.

[0141] Fig.32A and Fig.32B The complete tray 202 of the assay device is shown continuing to move inward until the target 148A of the assay device 100 is positioned along the second optical pathway 219. Continued inward movement results in the following simultaneous actions: the controller 207 turns on the illumination source 228 for backlighting the assay device 100. The first optical pathway shutter 227 closes the first optical pathway 218 to block illumination from reaching the color camera 216 via the first optical pathway 218. The digital color acquisition arrangement 214 focuses the color camera 216 on the target 148A backlit by the illumination source 228, ready to begin acquiring a microscope image of the body sample reacting with the liquid reagent 154A on the specimen slide panel 148.

[0142] Fig.33A 3B shows the tray 202 in its innermost position. During the continued inward movement of the complete tray 202 to its innermost position, the following actions occur: As the specimen slide panel 148 passes under the second optical pathway 219, the color camera 216 acquires a series of microscope images of the body sample reacting with the liquid reagent 154A on the specimen slide panel 148. The body sample on the specimen slide panel 148 is backlit by illumination from the illumination source 228 passing through the main outer tray component assembly 242 and the longitudinal slot 257.

[0143] When the target 151A of the assay device 100 is positioned along the second optical pathway 219 , the digital color acquisition arrangement 214 focuses the color camera 216 on the target 151A, ready to begin acquiring a microscopic image of the body sample reacting with the liquid reagent 154B on the specimen slide panel 151 .

[0144] As the specimen slide panel 151 passes beneath the second optical pathway 219, the color camera 216 acquires a series of microscope images of the body sample reacting with the liquid reagent 154B on the specimen slide panel 151. The body sample on the specimen slide panel 151 is backlit by illumination from the illumination source 228 that passes through the main outer tray member assembly 242 and the longitudinal slot 257.

[0145] The illumination source 228 is switched off.

[0146] Fig.34A and Fig.34BThe full tray 202 is shown moving outward until the inner tray component 233 begins to decouple from the outer tray component 232 to enable continued outward movement of the outer tray component 232 relative to the inner tray component 233 so that the inner tray component 233 can be reset to its assay device insertion / ejection position. The first optical path shutter 227 is opened.

[0147] Fig.35A and Fig.35B Outward movement of the outer tray component 232 relative to the stationary inner tray component 233 is shown. The restraining mechanism 234 begins to be activated, as evidenced by the compression spring 241 beginning to extend from its fully compressed length L2. The inner tray component 233 begins to depress the leading sample slide elevation component 246 and the trailing sample slide elevation component 248 beneath it. The plungers 254 and 256 begin to move away from the barrels 131 and 132. The sample slide 104 of the assay device is retained in its final uppermost sample inspection position by means of its sample slide securing arrangement 105, thereby preventing its reuse.

[0148] Fig.36A and Fig.36B Shown as Fig.25A and Fig.25B 202 in the same outermost position, thereby completing a complete operating cycle of the assay device 200 for obtaining diagnostic information from the assay device 100. The restraining mechanism 234 is fully activated, as evidenced by the compression spring 241 being at its fully uncompressed length L1. The leading sample slide elevation component 246 and the trailing sample slide elevation component 248 are blocked by the plate 253. In the outermost position of the tray, the inner tray component 233 is in its assay device insertion / ejection position relative to the outer tray component 232.

[0149] Fig.37A and Fig.37B The ejection of the assay device 100 from the tray well 203 is shown upon manual depression of the ejection button 204A. The spent assay device 100 can be safely discarded. The assay apparatus 200 is reset to snugly receive a new assay device 100 in its tray well 203.

[0150] Fig.38 and Fig.39 An assay device 200' is shown for use with an assay apparatus 100 having a built-in liquid reagent dispensing arrangement 106'. The assay device 200' has a similar construction to the assay device 200 and thus similar parts are similarly numbered. The assay device 200' differs from the assay device 200 in two respects, as follows: First, the internal tray component 233 contains the stopcock actuators 190A and 190B described above (see FIGS. 16 to 17). Fig.19B) for actuating the cocks 168A and 168B of the assay device. And second, the auxiliary outer tray component assembly 243 includes a pair of cutouts 264A and 264B for respectively receiving the cock actuation tabs 171A and 171B of the assay device after the cocks 168A and 168B are actuated to their liquid reagent dispensing positions. The assay device 200' has the same operation as the assay device 200, except that its cock actuators 263A and 263B open the cocks 168A and 168B of the assay device for liquid reagent dispensing purposes.

[0151] While the invention has been described with respect to a limited number of embodiments, it will be appreciated that numerous variations, modifications and other applications of the invention may be made within the scope of the appended claims.

Claims

1. A handheld assay device for use with a handheld sample collection tool, the handheld sample collection tool having a handle, a grip, and a sample collection tip for carrying a body sample, the assay device enabling electromagnetic radiation (EMR) examination of the body sample at at least one predetermined EMR wavelength, the assay device having a longitudinal assay device centerline and comprising: (a) a sleeve housing, comprising a sleeve housing top surface, a sleeve housing bottom surface opposite to the sleeve housing top surface, and a sleeve housing outer peripheral surface between the sleeve housing top surface and the sleeve housing bottom surface for defining the interior of the sleeve housing, The bottom surface of the sleeve housing includes at least one through hole for providing access to the interior of the sleeve housing, The outer peripheral surface of the sleeve shell includes a pair of opposite main side surfaces in the same direction as the center line of the longitudinal measuring device, and a pair of opposite auxiliary end surfaces transverse to the center line of the longitudinal measuring device, wherein the pair of opposite auxiliary end surfaces includes a leading auxiliary end surface and a trailing auxiliary end surface. The outer peripheral surface of the sleeve housing comprises a sample collection tip through hole for providing the sample collection tip with access to the interior of the sleeve housing; (b) a sample slide snugly received within the interior of the cartridge housing and slidably deployable from an initial, lowermost sample introduction position in an unused assay device to a final, uppermost sample inspection position in a used assay device, the initial, lowermost sample introduction position and the final, uppermost sample inspection position being distal and adjacent to the cartridge housing top surface, respectively, The cartridge housing top surface and the sample slide have at least one cartridge housing top surface panel and at least one sample slide panel, respectively, the at least one cartridge housing top surface panel and the at least one sample slide panel being aligned for defining an inspection line through the assay device, the at least one cartridge housing top surface panel and the at least one sample slide panel being transparent at an EMR wavelength of the at least one predetermined EMR wavelength, In an actuated state of the assay device, the sample slide panel is closely juxtaposed against the cartridge housing top panel; and (c) a built-in liquid reagent dispensing arrangement for dispensing liquid reagents onto said at least one specimen slide panel, said built-in liquid reagent dispensing arrangement comprising at least one longitudinally oriented barrel laterally of a centerline of said longitudinal assay device, Each of the barrels includes an exposed leading seal member facing the leading auxiliary end face and a trailing seal member disposed toward the trailing auxiliary end face, each of said barrels containing a liquid reagent between said leading seal and said trailing seal, Each of the barrels has a liquid reagent dispensing port for dispensing liquid reagent onto a corresponding sample slide of the at least one sample slide panel, The leading seal and the trailing seal have an initial pre-liquid reagent dispensing position in an unused assay device and a liquid reagent dispensing position, The leading seal is urged along the barrel from the initial pre-liquid reagent dispensing position to the liquid reagent dispensing position, The assay device enables a user to manipulate the sample collection tip through the sample collection tip through-hole to smear a body sample on the sample carrier in an unused assay device, and then the built-in liquid reagent dispensing arrangement is actuated to dispense liquid reagent on the body sample to react with the body sample, and the sample carrier is raised from its initial lowermost sample introduction position to its final uppermost sample inspection position via the at least one through-hole in the bottom surface of the sleeve housing, thereby preparing the used assay device for inspection of the body sample.

2. A device according to claim 1, wherein the sample carrier comprises at least one visually distinguishable target so that focusing can be performed thereon.

3. The device according to claim 1 further comprises a sample slide fixing arrangement for fixing the sample slide at the final uppermost sample inspection position, wherein the sample slide fixing arrangement realizes an irreversible displacement from the initial lowermost sample introduction position to the final uppermost sample inspection position.

4. The device according to any one of claims 1, wherein the tail sealing component is displaced along the barrel from the front of the liquid reagent dispensing port in the initial liquid reagent pre-dispensing position to pass through the liquid reagent dispensing port relative to the auxiliary front end face in the liquid reagent dispensing position.

5. The apparatus of claim 4, wherein at least one of the leading seal and the trailing seal component is visually distinguishable within the cartridge housing for enabling determination of the position of the at least one along the cartridge housing.

6. The device according to any one of claims 1, wherein the tail sealing component is a plug that is permanently deployed at the liquid reagent dispensing port and is pushed to rotate from a closed position at the initial liquid reagent pre-dispensing position to an open position at the liquid reagent dispensing position for dispensing liquid reagent.

7. The apparatus of claim 6, wherein the leading seal is visually distinguishable within the cartridge housing for enabling determination of the leading seal's position along the cartridge housing.

8. A device according to any one of claims 1 to 7, wherein the measuring device is preassembled with the handheld sample collection tool, and the leading auxiliary end face and the trailing auxiliary end face each include a central through hole, so that the sample collection tip of the handheld sample collection tool extends beyond the leading auxiliary end face and the handle of the handheld sample collection tool extends beyond the trailing auxiliary end face, and the measuring device and the handheld sample collection tool include a manually operated clamping arrangement for clamping the measuring device and the handheld sample collection tool together in a preassembled state before use, thereby preventing relative movement of the handheld sample collection tool relative to the measuring device.

9. The device according to claim 8, wherein the top surface of the sleeve housing includes a guide component, which hangs downward into the interior of the sleeve housing to guide the handheld sample collection tool to be slid out of the handheld measuring device for smearing the body sample on the sample slide.

10. The device according to claim 8, further comprising a removable protective foil for protecting the leading auxiliary end surface and the top surface of the sleeve housing, the protective foil being manually removed after the handheld sample collection tool is slidably removed from the measuring device.

11. An assay apparatus for use with a handheld assay device according to any one of claims 1 to 10 for diagnostic purposes of a body sample, the assay apparatus comprising: (a) Equipment housing, which contains: i) a tray having tray pockets for snugly and interchangeably receiving an assay device, and ii) a motorized arrangement for linear reciprocating movement of the tray between an outermost position relative to the device housing for interchanging assay devices and an innermost position relative to the device housing; (b) a plunger for insertion into the barrel of the assay device for dispensing the liquid reagent onto the body sample; (c) a sample slide elevation member for insertion through an underside through-hole of an assay device for advancing a sample slide of said assay device from its initial lowermost sample introduction position to its final uppermost sample inspection position; (d) a digital image acquisition arrangement for obtaining a digital image of at least a body sample contained in the assay device; and (e) A controller for controlling at least the motorised arrangement and the digital image acquisition arrangement.

12. The apparatus of claim 11, wherein inward movement of the tray from the outermost position to the innermost position results in the plunger being inserted into the barrel of the assay device before the tray reaches the innermost position.

13. An apparatus according to claim 11, wherein the inward movement of the tray from the outermost position to the innermost position causes the sample carrier elevation component to be inserted through the lower through hole of the measuring device before the tray reaches the innermost position for pushing the sample carrier of the measuring device to its final uppermost sample inspection position.

14. Apparatus according to any one of claims 11 to 13, wherein inward movement of the tray from the outermost position to the innermost position causes the digital image acquisition arrangement to acquire a digital image of at least a body sample contained in an assay device.

15. The apparatus of any one of claims 11 to 13, wherein the tray comprises: i) an outer tray part having said tray pocket, ii an inner tray member that longitudinally slides and reciprocates between an assay device insertion / ejection position for assay devices in said tray pockets at said outermost position and an actuated assay device position for assay devices in said tray pockets, and iii) a restraining mechanism for selectively restraining movement of the inner tray component relative to the outer tray component.

16. An apparatus according to claim 15, wherein the inner tray component includes the plunger and the through-slit, and the outer tray component includes a spring-biased sample carrier elevation component, and the arrangement is such that in the assay device insertion / ejection position, the plunger is not inserted into the barrel of the assay device and the inner tray component blocks the spring-biased sample carrier elevation component, and in the assay device actuation position, the plunger is inserted into the barrel of the assay device and the spring-biased sample carrier elevation component exits through the slit and enters the lower through-hole of the assay device for pushing the sample carrier of the assay device from its initial lowermost sample introduction position to its final uppermost sample inspection position.

17. An apparatus according to any one of claims 11 to 13, wherein the digital image acquisition arrangement comprises a single digital image camera, the single digital image camera having a first optical path for acquiring a first optical path image of a body sample and a second optical path for acquiring a second optical path image of the body sample, wherein the digital image acquisition arrangement is operable to instantly acquire images along the first optical path or the second optical path.

18. The apparatus according to any one of claims 11 to 13, further comprising a used assay device detector for determining whether an assay device newly inserted into a recess of the tray is an unused assay device prior to operation of the assay apparatus for diagnostic purposes.

19. The apparatus according to claim 18, wherein the used assay device detector optically detects the position of the seal of a newly inserted assay device, compares it with a reference position for an unused assay device, for determining whether the newly inserted assay device is an unused assay device.

20. The apparatus of claim 18, wherein the used assay device detector determines an electric motor power consumption of a leading seal for an initial displacement assay device, compares it to a reference electric motor power consumption for determining whether the newly inserted assay device is an unused assay device.

21. An apparatus according to any one of claims 11 to 13, for use with an assay device according to claim 6, wherein the apparatus housing comprises a stopcock actuator for rotating a stopcock from a closed position at the initial pre-liquid reagent dispensing position to an open position at the liquid reagent dispensing position for dispensing liquid reagent, the inward movement of the tray from the outermost position to the innermost position causing the plunger to be inserted into the barrel of the assay device before the tray reaches the innermost position.

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