Patent Publication Number: US-2023160444-A1

Title: Apparatus for quickly displaying coronavirus test result

Description:
CROSS REFERENCE TO RELATED APPLICATION 
     This application is a continuation of U.S. application Ser. No. 17/069,808, filed Oct. 13, 2020. The contents of the above-identified application is incorporated herein by reference in their entirety. 
    
    
     FIELD OF THE INVENTION 
     The present invention generally relates to the technology of reading fluorescent signals for coronavirus test result. More particularly, the invention is related to an apparatus for quickly displaying coronavirus test result by providing consistent and accurate on-site readings of fluorescence signals, with which an ordinary person can operate a coronavirus test at home without need a medical professional&#39;s assistance. 
     BACKGROUND OF THE INVENTION 
     Fluorescence and Colloidal Gold Conjugate are two main signal rendering methods in the diagnostic fields. Fluorescent immunoassay functions by marking the target analyte with a specially designed antibody, which emits light after exposure to UV light sources. 
     While the fluorescent method is generally more sensitive than the Colloidadel Gold method, tests targeting OTC or Point of Care market use mostly Colloidal Gold method. The main reason is that current Colloidal Gold immunoassay design performs better in terms of usability and consistency in non-professionals. The colloidal gold allows direct coloration on the test strips, where no additional equipment or training is needed; meanwhile, using fluorescent immunoassay requires a specialized reader that shines UV light and reads the response signals. 
     The readers in the market right now are usually designed for high-throughput laboratories, which means they are capable for automated high-volume testing but they are too expensive and they require much more sophisticated training for the public. This is a significant drawback as having the sensitivity advantage not available to the public significantly reduces chances of early diagnosis. 
     In the context of COVID-19 pandemic, what is needed is an apparatus for consistent and accurate on-site readings of fluorescence signals in a coronavirus test, with which an ordinary person can operate a coronavirus test at home or work place without need of a medical professional&#39;s assistance. 
     SUMMARY OF THE INVENTION 
     The present invention discloses an apparatus for quickly displaying coronavirus test result by providing consistent and accurate on-site readings of fluorescence signals, with which an ordinary person can operate a coronavirus test at home without need a medical professional&#39;s assistance. 
     In one preferred embodiment, the present invention teaches an apparatus for consistent and accurate on-site readings of fluorescence signals, wherein a user directly reads a fluorescent light qualitatively instead of using electronic sensors. The fluorescent light is excited from a fluorescent source in a site of interest of a target assay. The apparatus includes a light source for generate an excitation light for exciting the fluorescent source of the assay to generate a fluorescent light, a component for accurately transmitting the excitation light and the fluorescent light with less noise or reflection, a component for consistent detecting of the fluorescent source by bare eyes with minimal health risks, and a user control system that requires minimal training. 
     In another preferred embodiment of the present invention, the apparatus further includes a semi-closed chamber which is used as a backbone to contain all other components. Preferably, the chamber is made of impermeable materials that can shield the light transmission channels from suspending particles and environmental light noises. 
     In another preferred embodiment of the present invention, the apparatus backbone is made of a designated color to better contrast the signal fluorescent light. 
     In another preferred embodiment of the present invention, the apparatus contains a docking space, through which the apparatus is designed to a shape such that the docking space closely fits and stationizes the assay to be analyzed. The apparatus further includes a plurality of anchor points that reduce spatial variability of all other components, consequently limiting the user&#39;s variability in terms of shaking or wrong direction during reading process. 
     In another preferred embodiment of the present invention, wherein the chamber is made of PVC. 
     In another preferred embodiment of the present invention, the light source is generated by using two UV-C LED lights, each of the UV-C LED lights having frequency approximately 365 nm and power approximately 0.5 Watts. 
     In another preferred embodiment of the present invention, the apparatus further includes a viewing window and a plurality of spectral filtrations which is applied either to the viewing window or the light source in order to avoid coincidence of the fluorescent light and the excitation light and prevent the user&#39;s body from exposure to the lights. 
     In another preferred embodiment of the present invention, the excitation light source is arranged to be not directly exposed or imposing any strong reflection into the user&#39;s eyes for safety and sensitivity concerns. 
     In another preferred embodiment of the present invention, the excitation light sources are installed in an arrangement such that the excitation light primarily illuminates the site of interest of the assay to be analyzed. 
     In another preferred embodiment of the present invention, the site of interest of the assay to be analyzed and the excitation light source is placed at a 45 degrees angle and 10 mm distance, which results in least deflection. 
     In another preferred embodiment, the present invention teaches a method for operating the apparatus for assist analysis of the fluorescence source of the assay to be analyzed and the apparatus further includes a program, size and a plurality of specifications of the excitation light source, a docking space and a power button. The method includes the following steps: (1) making sure the program, size and the plurality of specifications of the excitation light source matching the assay to be analyzed; (2) inserting the assay to be analyzed into the docking space; (3) turning on the apparatus by pressing the power button; (4) emitting the excitation light to shine on the site of interest of the assay to be analyzed and excite the fluorescent source within the assay to be analyzed, which then emits fluorescent light as responses; and (5) observing the site of interest by the user according to the instruction for use of the assay to be analyzed. 
     The advantages of this invention are numerous. First, the invention is economic and easy to use, which allows for the public to afford and operate fluorescent-based tests at frequent interval without professional guidance. This allows rapid fluorescent testing at small or medium events like sport festival, which was not feasible priorly due to the complexity and cost of laboratory-level fluorescence readers. As mentioned in the background of the invention, fluorescence-based tests are generally more sensitive than current OTC methods. This difference in sensitivity, when amplified by mass implementations, can save a significant number of people. Second, the invention enables consistent and safe reading of fluorescent signals comparing to other lower-priced on-site fluorescence reading methods, such as handheld ultraviolet lights. This is an important improvement as the readability of fluorescence signals are sensitive to environments and users&#39; habits, which could lead to false readings. 
    
    
     
       BRIEF DESCRIPTION OF DRAWINGS AND TABLES 
         FIG.  1    is a schematic representation of a perspective view of the casing of the apparatus according to the present invention, with a sliding member for holding assay holder  301 ; 
         FIG.  2    is a schematic representation of a lateral view of the apparatus of  FIG.  1   , with the assay holder  301  inserted; 
         FIG.  3    is a schematic representation of a posterior view of the apparatus of  FIG.  1   ; 
         FIG.  4    is a schematic representation of a top view of the apparatus of  FIG.  1   , with the assay holder  301  inserted; 
         FIG.  5    is a schematic representation of a bottom view of the apparatus of  FIG.  1   , with the assay holder  301  inserted; 
         FIG.  6    is a schematic representation of a perspective section view of the apparatus of  FIG.  1   , with the assay holder  301  inserted but the upper casing  101  removed; 
         FIG.  7    is a schematic representation of a perspective section view of the apparatus of  FIG.  1   , without showing the upper casing  101  and the assay holder  301 ; 
         FIG.  8    is a schematic representation of a perspective section view from the bottom of the apparatus of  FIG.  1   , showing the assay holder  301  inserted, but not showing the lower casing  102 ; 
         FIG.  9    is a schematic representation of a perspective section view from the bottom of the apparatus of  FIG.  1   , without showing the lower casing  102 ; and 
         FIG.  10    illustrates an exploded view of the apparatus assembly of the preferred embodiment, including the assay holder  301  as a reference. 
         FIG.  11    illustrates an exploded view of the assembly and sub-components of the assay holder  301  and the assay to be analyzed  401 . 
         FIG.  12    illustrates a perspective section view of the assay to be analyzed  401  placed in the bottom casing  3011  of the assay holder  301 . 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Terms and Definitions 
     In this invention, a user is the operator who physically handles the apparatus, and a subject is the human or animal whose specimen were drawn. 
     An assay refers to or means a test mechanism that analyzes clinical specimens and inform about specimen composition, and an analyte refers to a substance of interest that could be found in specimen. 
     A fluorescent source refers to or means a fluorophore, or a biochemical compound that can re-emit light upon light excitation. For example, a fluorescent source could refer to Green Fluorescent Proteins or fluorescent microspheres such as Polystyrene nanoparticles. 
     A site of interest refers to or means a place, an area, a component, a channel, or a side of the assay where results are delivered, or places where reaction happens most intensively. For example, it could be the antibody-labeled band for immunoassays, where fluorescence signal at the band informs about the detectable presence of the target analyte; or, it could refer to the reaction chamber for microfluidics. 
     A light source for generating an excitation light, or excitation light source means an apparatus or mechanism that is capable of emitting light of frequencies within the significant adsorption spectrum of the fluorescent source at reasonable intensity. For example, a 0.5 W light emitting diode of frequency 365 nm is qualified as a excitation light source, as the light it emits can induce fluorescence of polystyrene fluorescent microsphere continuously, and the fluorescent light emitted is at the intensity visible to average users. 
     The present invention discloses an apparatus for consistent and accurate on-site readings of fluorescence signals, wherein a user directly reads a fluorescent light qualitatively instead of using electronic sensors. While the present invention may be embodied in many different formulas for the purpose of promoting an understanding of the principles of the invention, reference will be made to the embodiments illustrated in the drawings, tables and specific language will be used to describe the same. It will nevertheless be understood that no limitation or restriction of the scope of the invention is thereby intended. Any alterations and further implementations of the principles of the invention as described herein are contemplated as would normally occur to one skilled in the art to which the invention relates. 
     In one preferred embodiment as illustrated in  FIGS.  1 - 10   , the invention teaches an apparatus for quickly displaying coronavirus test result by providing consistent and accurate on-site readings of fluorescence signals, with which an ordinary person can operate a coronavirus test at home without need a medical professional&#39;s assistance. Using the apparatus, a user directly reads a fluorescent light qualitatively without the necessity of electronic sensors. 
       FIG.  1    shows a perspective view of the casing of the apparatus according to the present invention, with an assay holder  301  which is slidably inserted into the internal chamber of the apparatus.  FIG.  2    shows a lateral view of the apparatus, with the assay holder  301  slidably inserted. The apparatus is symmetric to its longitudinal direction.  FIG.  3    shows a posterior view of the apparatus.  FIG.  4    shows a top view of the apparatus, with the assay holder  301  inserted.  FIG.  5    shows a bottom view of the apparatus, with the assay holder  301  slidably inserted.  FIG.  6    shows a perspective section view of the apparatus&#39;s lower casing  102 , with the assay holder  301  slidably inserted but the upper casing  101  is removed for illustration purpose.  FIG.  7    shows a perspective section view from the bottom of the apparatus&#39;s lower casing  102  without showing the upper casing  101 , and the assay holder  301  is not inserted.  FIG.  8    shows a perspective section view from the bottom of the apparatus, with the assay holder  301  slidably inserted, without showing the lower casing  102  for illustration purpose.  FIG.  9    shows a perspective section view from the bottom of the apparatus&#39;s internal structure, without the lower casing  102 .  FIG.  10    shows an exploded view of the apparatus assembly of the preferred embodiment, including the assay holder  301  as a reference.  FIG.  11    shows an exploded view of the assay/holder complex  301  and  401  of the preferred embodiments.  FIG.  12    shows a perspective section view of the assay to be analyzed  401  placed in the bottom casing  3011  of the assay holder  301 . 
     The apparatus is used to analyze an assay that test a specimen of human saliva, blood, respiratory swabs, etc. The assay uses fluorescence signal to deliver the result of the test. The assay, therefore, contains a fluorescent source that interact with the target analyte present in the specimen, and is delivered to the site of interest when the assay is ready to be analyzed. The assay is analyzed by shining excitation light to the area of interest. If fluorescent source is present, the excitation light activates the fluorescent source and induces fluorescent emission, namely fluorescent signal. The apparatus also includes an excitation light source for generating an excitation light for exciting said fluorescent source of said target assay to generate said fluorescent light, a component for accurately transmitting the excitation light and the fluorescent light with less noise or reflection, a component for consistent detecting of the fluorescent source by bare eyes with minimal health risks, and a user control system that requires minimal training. Here, the component for accurately transmitting the excitation light means apparatus design, electronics, optics, or spatial arrangements that impact direction, intensity, spread, or frequency of light, or noise-to-signal ratio of the fluorescent signal, or temporal stability of light emission. For example, and it can be the arrangement of directly placing excitation light source facing the site of interest, or it could be optics that focus excitation light on the site of interest. The component for consistent and safe detecting of the fluorescent source means apparatus design, gadgets, electronics, or programs that limits user&#39;s variability in terms of shaking, timing, angle, distance, directions, or apparatus design, gadgets, electronics, programs and optics that prevent overheating or operator&#39;s harmful exposure to lights. For example, it could be automated program that turns off the excitation light source—which usually covers ultraviolet spectrum—after an interval of time. The user control system includes an interface that the user can physically interact with to change the parameters or functioning status of the apparatus. For example, it could be a button, a knob, a screen, or it could be a separate computer program. 
     For many usage scenarios like respiratory viral infection test, pregnancy test, or serological cancer screening, the assay is made of a long and narrow lateral flow test strip that takes in liquid specimen. This is especially the case for rapid or POC/OTC claim tests for timesaving and reducing required sample volume. In one preferred embodiment of the present invention, also referring to  FIG.  11   , the assay is a rapid COVID-19 fluorescent immunoassay  401 . Although the test strip itself often contains all components needed for running valid tests, assay strips are usually enclosed in assay holders for stability considerations.  FIG.  11    demonstrates an example of test strips enclosed in an assay holder that is designed more for non-professional uses.  301 . The assay  401  includes a sequence of components that processes the test-ready sample, from first to contact with the specimen to the last are: Sample Pad  405 , Fluorescent Microsphere Reservoir  404 , Area of the interest  402 , which can be further broke down into the Positive Band (T Band)  4021  and the Control band (C Band)  4022 , and finally Adsorption Pad  403 . All of these components are laid on a backing made of impermeable materials (e.g. PVC) and a nitrocellulose membrane for capillary action. When clinical specimens are well-prepared, such as completed dissolved in buffer or completed chemolysis, samples are added to the sample pad  405 . The sample pad  405  slight adsorbs the specimen and keep the specimen inside the assay  401 . The adsorbed specimen will move towards the other end due to capillary action. As the specimen travels the assay, it encounters the fluorescent source of this assay: analyte specific fluorescent microsphere reservoir  404 . The fluorescent microsphere travel along with the specimen, but when COVID-19 analyte, e.g. SARS-CoV-2 n protein or s protein, is present in the specimen, the fluorescent microsphere, or fluorophore, binds with the COVID-19 analyte by antibody labeling. As it passes through site of interest  402 , COVID-19 analyte is captured by the antibodies precoated on Positive band  4021  that is specific to the COVID-19 analyte. As a result, fluorophores that attached to COVID-19 analytes are also stopped at the Positive Band  402 . The aggregation of fluorophore makes it capable of emitting fluorescent signal that are observable by average user with bare eyes. Those fluorophores that are not attached or do not have COVID-19 analyte to attached to continue to travel with the rest of the specimen. These eventually reach and get stored by the Adsorption Pad  403 , which prevents back-flow. The C-line  4022  works in a similar mechanism. 
     Although the test strip itself often contains all components needed for running valid tests, assay strips are usually enclosed for stability considerations.  FIG.  11    demonstrates an example of test strips enclosed in an assay holder that is designed for non-professional uses. The assay holder  301  includes an upper casing  3011  and a bottom casing  3012 . As  FIG.  12    indicates, the test assay is placed in the bottom casing  3012  and secured by walls  3016 . The two casings  3011  and  3012  are joined by pairs of connectors  3015  found on both pieces. There are two openings on the upper casing  3011 , including an inlet  3013  where clinical specimen, such as serum or respiratory samples dissolved in transfer media, or other liquid reagents are loaded; and a view window  3014  that allows user to read fluorescent signals from site of interest  402 , particularly the bands  4021  and  4022 . The sample inlet  3013  is aligned with the sample pad  405 . The view window  3014  is aligned with and should cover the area of interest  402  so that user may get a full view. The casing  3011  and  3012  shields components of the assay  402  that are irrelevant to result reading from the users. 
     The above mechanisms and arrangement of the rapid COVID-19 fluorescent immunoassay  401  and assay holder  301  is a good representation of similar tests in the industry. 
     In another preferred embodiment of the present invention, the apparatus further includes a semi-closed chamber defined by the upper casing  101  and the bottom casing  102 , which is used as a backbone to contain all other components including the slidable assay holder  301 . The casings of the chamber are made of impermeable materials that can shield the light transmission channels from suspending particles and environmental light noises. 
     In another preferred embodiment of the present invention, the apparatus backbone is made of a designated color, such as black or dark gray, to better contrast the signal fluorescent light. 
     In another preferred embodiment of the present invention, the apparatus contains a docking space  108 , wherein the apparatus is designed to a shape such that the docking space  108  closely fits and stationizes the assay to be analyzed  401  or assay/holder complex  401  and  301 . The apparatus further includes a plurality of anchor points, that reduces spatial variability of all other components, consequently limiting the user&#39;s variability in terms of shaking or wrong direction during reading process. 
     In another preferred embodiment of the present invention, the sample inlet of the assay holder  301  is intentionally left outside the apparatus&#39;s docking space  108  in order for the user to visually monitor the specimen, for situations such specimen running dry. 
     In another preferred embodiment of the present invention, wherein the casing of the chamber  101  and  102 , is made of PVC. 
     In another preferred embodiment of the present invention, the light source  107  includes two UV-C LED lights with 365 nm frequency and 0.5 Watts power. 
     In another preferred embodiment of the present invention, the apparatus further includes a viewing window  103  and a plurality of spectral filtrations, such as colored translucent PVC films that blocks light with certain frequency. The plurality of spectral filtrations are applied either to the viewing windows  103  or the light source  107  in order to prevent coincidence of the fluorescent light and the excitation light or avoid human body&#39;s direct exposure to unnecessary and unintended lights. 
     In another preferred embodiment of the present invention, the excitation light source  107  is arranged to be not directly exposed or imposing any strong reflection into the user&#39;s eyes for safety and sensitivity concerns. 
     In another preferred embodiment of the present invention, the excitation light sources  107  are installed in an arrangement such that the excitation light primarily illuminates the site of interest  402  of the assay to be analyzed  401   
     In another preferred embodiment of the present invention, the site of interest of the assay to be analyzed and the excitation light source is placed at a 45 degrees angle and 10 mm distance, which results in least deflection. 
     In another preferred embodiment, the present invention teaches a method for operating the apparatus for assist analysis of the fluorescence source of the assay to be analyzed and the apparatus further includes a program, size and a plurality of specifications of the excitation light source, a docking space and a power button. The method includes the following steps:
         (a) Make sure the program, size and the plurality of specifications of the excitation light source matching the assay to be analyzed;   (b) Insert the assay to be analyzed into the docking space;   (c) Turn on the apparatus by pressing the power button;   (d) Emit the excitation light to shine on the site of interest of the assay to be analyzed and excite the fluorescent source within the assay to be analyzed, which then emits fluorescent light as responses; and   (e) The user observes the site of interest according to the instruction for use of the assay to be analyzed.       

     Referring to  FIG.  10    that illustrates an exploded view of the apparatus assembly of the preferred embodiment and  FIG.  11    that illustrates a component of the assay to be analyzed/holder complex. The components of the assay can be grouped into two categories: the apparatus category, and the assay category. 
     The apparatus category includes the casing and main components, and interface components. More particularly, the apparatus includes the following parts:
       101 —Upper Casing     102 —Lower Casing     103 —View Window     104 —Insert Opening     105 —Connector     106 —Printed Circuit Board (lighting)     107 —Excitation Light Source (light beads)     108 —Main Docking Space     109 —Printed Circuit Board (Control Panel)     110 —Placeholder     111 —Opening for the Button     112 —Opening for the Charging Port     113 —Docking space   

     And the interface includes the following:
       201 —Status Light     202 —Button Interface     203 —Charging Port     204 —Chargeable Battery     205 —Button Trigger   

     There are many ways assays can be designed and used with the apparatus based on intended use.  FIG.  10    and  FIG.  11    illustrates one example, with a commercially common setup that uses lateral flow fluorescent immunoassay as the assay to be analyzed, including the following:
       301 —Assay holder     3011 —Upper casing of the Assay holder (sub-component of  301 )     3012 —Lower casing of the Assay holder (sub-component of  301 )     3013 —Inlet for Sample/Buffer/Analyte Addition (sub-component of  301 )     3014 —View window of the Assay holder (sub-component of  301 )     3015 —Connectors of the Assay holder (sub-component of  301 )     3016 —Plate for Assay to be analyzed Placement (sub-component of  301 )     3017 —Cavity (sub-component of  301 )     401 —Assay to be analyzed (Test strip)     402 —Area of Interest of the Assay to be analyzed (sub-component of  401 )     4021 —Control Line of the Assay to be analyzed (sub-component of  402 )     4022 —Diagnostic Line of the Assay to be analyzed (sub-component of  402 )     403 —Adsorption Pad of the Assay to be analyzed (sub-component of  401 )     404 —Fluorescent Microsphere Reservoir of the Assay to be analyzed (sub-component of  401 )     405 —Sample Pad of the Assay to be analyzed (sub-component of  401 )   

     In terms of spatial arrangements, all essential components of the apparatus are coupled together in the space between the upper casing  101  and lower casing  102 . The two casings are fixed to each other by pairs of connectors  105 . 
     Internally, the upper and lower casing tightly connect to each other, which secures smaller components in space, including: excitation light emitter  107 , printed circuit board for lights  106 , and the control/power components  202 ,  205 ,  109 ,  204 . The excitation light emitter  107  is soldered to PCB  106 , forming a light/board complex. Two light/board complexes are installed on top of the edge of the lower casing  102 , one on each side, with the excitation light emitter  107  facing the main docking space  108 . The PCB  106  both serves to power to emitter  107  and to prevent light from reflecting into the docking space. In the preferred embodiment of this invention, the excitation light emitter  107  is positioned in 45 degrees angle with 10 mm distance to the site of interest  402 . This arrangement hides the light emitter  107  from the user&#39;s eyes, but also the excitation light to fully cover the site of interest. 
     The control/power components are located in the posterior cavity. The button interface  202  is on the topmost layer, which is resting on top of the trigger  205 . Both the button  202  and the button trigger  205  are stationed on the main control PCB  109 . The cable charging port  203  is attached to the side of the main control PCB  109 . The rechargeable battery  204  is stored in the lower compartment, underneath the control PCB. In some embodiments, replaceable dry batteries will be used instead of the rechargeable battery  204 , and consequently the charging port  203  will be removed. 
     Externally, the casing has several openings for different purposes. In the front there is an entry opening for assay  104  which leads to the main docking space  108 . The shape of outer casing  101  and  102 , the entry opening  104 , and the main docking space  108  should fit the assay holder  301 , such that the area of interest  402  can be fully illuminated by the excitation light emitter  107 . In the back there is an entry-port opening  112  that fits a cable charging port  203 . On the top there are two large openings. One of them is the view window  103 . The view window  103  is vertically above the area of interest  402  and aligning the view window of the assay holder  3014 , so that users may view the area of interest  402  without distortions. The dimension of the view window  103  should be the same size as the area of interest  402 ; however, the view window  103  should not be too wide such that the excitation light emitters  107  are directly exposed to the user, such that the user may get a full view of the area of interest without safety concerns. The other opening is the opening for the button interface  111 , which leaves space for the button set  202  &amp;  205  and the status light  201 . 
     In one preferred embodiment, the upper and lower casings  101 ,  102  were made of PVC, which is an example of impermeable materials that can shield the light transmission channels from suspending particles and environmental light noises. Further, the color of the casings  101 ,  102  are set to be black to better contrast the signal fluorescent light, which is conventionally light blue or green. 
     In one preferred embodiment, two UV-C LED lights of 365 nm frequency and 0.5 Watts power were used as excitation light emitter  107 . Choice of light source could vary substantially based on use, but most commercially available fluorophores in the diagnostic fields are excited to visible level by this wavelength and power. Although not needed in most cases, spectral filtrations can be applied either to the viewing window or the light source in order to prevent coincidence of the fluorescent and excitation light, or to filter out dangerous frequencies of lights. 
     The electronic circuits of the invention are implanted in Printed Circuit Boards  107  &amp;  109  for portability concerns. The electronics are powered by the rechargeable battery  204 . When the user presses the button  202 , the signal activates the status light  201  and excitation light emitter  107 . The system turns on for 20 seconds and automatically turns off afterwards to prevent overheating and potential damage to the assay or eyes. 
     The above detailed description of the apparatus for consistent and accurate on-site readings of fluorescence signals is illustrative but not restrictive. Many more embodiments may be added within the limit of the scope. 
     Any modifications and adoptions without departing from the scope and spirit as set forth in the claims will still be within the protection of this invention.