Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-18) in the reply filed on 5/9/26 is acknowledged.
Claims 19-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3, 5-10, 13 and 18 arejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3, line lines 3 and 5, recite “absorption/reflection-based image”. It is not clear if this limitation means --absorption and reflection--, or --absorption or reflection--.
Similarly, claim 5, line 3 recites the same limitation.
Similarly, claim 8, line 3 recites the same limitation.
Likewise, claim 10, line 3 recites the same limitation.
Claim 13, line 3 also recites the same limitation.
Claim 18, line 2 also recites the same limitation.
For examination purposes, the limitation is interpreted as --absorption or reflection--. Clarification is required.
Claims 6, 7 and 9 are rejected since they depend from one of the above claims without further clarifying the vagueness.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 3, 7, 8, 10-12 and 15-17 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by US 20190226985 (hereinafter “Roberts”).
Applicant’s claim 1 recites:
a multi-modal diagnostic test reading apparatus, comprising:
a diagnostic test assembly receiving component;
at least one image sensor;
a plurality of light sources having respective different spectral properties;
and a controller; wherein the controller is configured to:
control operation of the light sources and the at least one image sensor to acquire a plurality of images, each of the acquired images representing at least a corresponding portion of the diagnostic test assembly as illuminated by a corresponding one of the light sources;
and(ii) process the acquired images to determine a diagnostic test result of the diagnostic test, the diagnostic test result being dependent upon the processed images representing illumination by respective ones of the light sources having respective different spectral properties.
Roberts discloses the presently claimed limitations as follows. (See further below for discussion).
According to a first aspect of the invention there is provided an analytical test device including two or more sets of emitters, each set of emitters comprising one or more light emitters configured to emit light within a range around a corresponding wavelength. Each set of light emitters is configured to be independently illuminable. The test device also includes one or more photodetectors arranged such that light from each set of emitters reaches the photodetectors via an optical path comprising a sample receiving portion. The emitters and photodetectors are configured such that, at the sample receiving portion of the optical path, a normalised spatial intensity profile generated by each set of emitters is substantially equal to a normalised spatial intensity profile generated by each other set of emitters. The test device also includes a liquid transport path comprising a first end, a second end and a liquid sample receiving region. The liquid transport path is configured to transport a liquid sample received in the liquid sample receiving region towards the second end and through the sample receiving portion of the optical path. Para. 0009.
Absorbance measurements obtained using the two or more sets of emitters may be de-convoluted (de-mixed) to quantify the concentration of one or more analytes whilst also compensating for optical scattering due to defects or other inhomogeneities of a sample. Para. 0010.
The analytical test device may include a plurality of first and second emitters arranged in an array. Para. 0026.
The photodetectors may take the form of photodiodes, photoresistors, phototransistors, complementary metal-oxide semiconductor (CMOS) pixels, charge coupled device (CCD) pixels, photomultiplier tubes or any other suitable photodetector. Para. 0027.
The optical path may be configured such that the photodetectors receive light transmitted through the sample receiving portion of the optical path. Para. 0028.
The optical path may be configured such that the photodetectors receive light reflected from the sample receiving portion of the optical path. Para. 0029.
The photodetectors may form an image sensor arranged to image all or a portion of the sample receiving portion of the optical path. Para. 0030.
Referring to FIGS. 8 to 10, a lateral flow test strip 18 may be passed through the sample receiving portion 8 of the optical path 7, and the absorbance values A(x) measured as a function of position x along the porous strip 19 of the lateral flow testing device 18. The absorbance values A(x) are determined based on the difference in transmittance or reflectance when a sample 9 occupies the sample receiving portion 8 and a reference condition, for example, the absence of a sample 9. Para. 0140.
Alternatively, for measurements in transmission, a simple calculation may be performed by dividing the transmission of the light 5 from the first emitter 2 by the transmission of the light 6 from the second emitter 3. Para. 0151.
If further samples 9 are to be measured, then the next sample 9 may be placed (step S7). Alternatively, if there are additional regions of interest on the same sample 9, for example if the sample 9 is a lateral flow test strip 18 having more than one test region 20, the sample 9 may be repositioned with the next region of interest within the sample receiving portion 8. Para. 0152.
Referring also to FIG. 14, the optical path 7 may be configured so that the photodetector(s) 4 receive light 5, 6 transmitted through the sample receiving portion 8 of the optical path 7. For measurements in transmission, the light emitter(s) 2, 3 and photodiode(s) 4 may simply be spaced apart by a gap which corresponds to the optical path 7. The sample receiving portion 8 of the optical path 7 then corresponds to the part of the gap which is occupied by a sample 9 when the sample 9 is received into the analytical testing device 1. Para. 0155.
If a sample 9 in the form of a lateral flow test strip 18 is used, the lateral flow test strip 18 may be arranged with a testing region 20 positioned between the light emitter(s) 2, 3 and photodiode(s) 4. The sample receiving portion 8 of the path 7 corresponds to the thickness of the lateral flow test strip 18 which intersects the optical path 7. Para. 0156.
Additional optical components may be included in the optical path 7. For example, the light from the light emitters 2, 3 into the optical path 7 and/or the light from the optical path 7 to the photodiode(s) 4 may be restricted by slits or other apertures. Optionally, a diffuser, one or more lenses and/or other optical components may also be included in the optical path 7. Para. 0157.
Referring also to FIG. 15, an analytical test device 1 may alternatively be configured so that the photodetector(s) 4 receive light reflected from the sample receiving portion 8 of the optical path 7. For example, when the analytical testing device 1 is arranged to receive samples in the form of lateral flow test strips 18, the light emitters 2, 3 may be arranged to illuminate a region of interest of a lateral flow test strip 18 received into the test device 1 at first angle θ.sub.1, and the photodiode(s) 4 may be arranged to receive light reflected from the lateral flow test strip 18. Para. 0158.
Additional optical components may be included in the optical path 7. For example, the light from the light emitters 2, 3 into the optical path 7 and/or the light from the optical path 7 to the photodiode(s) 4 may be restricted by slits or other apertures. Optionally, a diffuser, one or more lenses and/or other optical components may also be included in the optical path 7. Para. 0159.
Referring also to FIG. 16, the analytical test device 1 may include a number of photodetectors 4 arranged in an array to form an image sensor 24. For example, the image sensor 24 may form part of a camera. An image sensor 24 may be arranged to image all of, or a portion of, the sample receiving portion 8 of the optical path 7. For example, when a lateral flow test strip 18 is received into an analytical test device 1, the image sensor 24 may be arranged to image one or more test regions 20 and the surrounding areas of the porous strip 19. A lateral flow test strip 18 may include one or more pairs 25, each pair 25 including a testing region 20 and a control region 26, and the image sensor 24 may be arranged to image the one or more pairs 25 at the same time. An image captured using the second, reference wavelength λ.sub.2 may be subtracted from an image captured using the first, measurement wavelength λ.sub.1, in order to compensate for background variance due to inhomogeneity of the fibres 22 making up the porous strip 19. The subtraction may be weighted using a weighting factor α when the absolute intensity of illumination from the first and second emitters 2, 3 is not substantially equal and/or when the sensitivity of the image sensor 24 differs between the first and second wavelengths λ.sub.1, λ.sub.2. Para. 0160.
An image sensor 24 may be used to image transmitted or reflected light. Additional optical components may be included in the optical path 7. For example, the light from the light emitters 2, 3 into the optical path 7 and/or the light from the optical path 7 to the photodiode(s) 4 may be restricted by slits or other apertures. Optionally, a diffuser, or more lenses and/or other optical components may also be included in the optical path 7. Para. 0161.
The liquid transport path 41 intersects the sample receiving portion 8 of the optical path 7 and the optical absorbance of the porous strip 19 in the sample receiving portion may be monitored as a function of time. Such measurements may sometimes be referred to as “dynamic” or “kinetic” measurements. For example, if a lateral flow test strip 18 is arranged with a test region 20 within the sample receiving portion 8, then the development of the concentration of labelling particles 21 may be tracked as a function of time by measuring the absorbance of the test region 20 at the first and second wavelengths λ.sub.1, λ.sub.2 as a function of time. If a lateral flow test strip 18 includes additional regions of interest, for example control regions 26 or further test regions 20, then the analytical test device 1 may be provided with additional pairs of emitters 2, 3 and photodetector(s) 4. Para. 0164.
The liquid transport path 41 need not be a porous strip 19 of a lateral flow test strip 18. Alternatively, the liquid transport path 42 may take the form of one or more channels of a microfluidic device. Para. 0165.
Referring to FIG. 19, light 5, 6 from the first and second emitters 2, 3 may be introduced onto the optical path 7 through a slit 46 defined by a pair of slit members 47 separated by a gap. Para. 0168.
Optionally, a diffuser 48 may be arranged at a point between the slit 46 and the emitters 2, 3. One or more lenses (not shown) may also be included to collect and/or focus light 5, 6 from the light emitters 2, 3. Para. 0170.
Coupling light 5, 6 from the first and second emitters 2, 3 into the optical path 7 through a slit 46 may be used for measurements in transmission or reflection. Para. 0173.
Referring also to FIG. 22, in some examples of an analytical test device 1, the optical path 7 need not include any conventional optical components. For example, a light emitting diode array 60 may simply be arranged at the other end of a plain optical path 7 to a photodetector 4, i.e. the optical path 7 only includes the sample receiving portion 8. The light emitting diode array 60 includes at least two light emitting diodes, i.e. one first light emitter 2 and one second light emitter 3. The light emitting diode array 60 may be composed of a plurality of light emitting diode pixels of similar dimensions to those found in light emitting diode display devices for computers, televisions and so forth. The light emitting diode array 60 may include a mixture of first and second emitters 2, 3. Para. 0174.
Where samples 9 include multiple regions of interest, the sample 9 may be moved in front of the light emitting diode array 60 to scan the sample 9. Alternatively, the light emitting diode array 60 and corresponding photodetector 4 may be moved to scan the sample 9. Alternatively, a light emitting diode array 60 and one or more photodetectors 4 may be arranged corresponding to each region of interest of the sample 9 so that each region may be measured concurrently. Para. 0175.
When a sample is in the form of a lateral flow test strip 18 which extends longitudinally in a first direction x, transversely in a second direction y and has a thickness in a third direction z, a light emitting diode array 60 may extend for substantially the width of the lateral flow test strip 18 in the transverse y direction and for a relatively shorter distance in the longitudinal x direction. If the lateral flow test strip 18 is mounted in a sample mounting stage 29 including a window for transmission measurements, then the light emitting diode array 60 may extend for substantially the width of the lateral flow test strip 18. Alternatively, the lateral flow test strip 18 may be mounted fixedly with respect to the analytical test device 1, and a pair of an LED array 60 and a photodetector 4 may be provided corresponding to each test region 20 and/or control region 26. Para. 0178.
Referring to FIGS. 25 and 26, one way to implement a light emitting diode array 60 is to stack the first and second emitters 2, 3 on top of each other. Each first light emitter 2 takes the form of a light emitting diode with a peak emission at the first wavelength λ.sub.1 and the corresponding second light emitter 3 takes the form of a light emitting diode with a peak emission at the second wavelength λ.sub.2. The first and second light emitters 2, 3 may be separately addressed to allow for alternating illumination. Para. 0181.
A diffuser 48 may optionally be included between each light emitting diode array 60 and the corresponding slit 46. Para. 0188.
Roberts also discloses that the device comprises a controller to perform the disclosed processes. See for example the following.
The controller 27 may be configured to illuminate the first emitters 2 and obtain a first set of measurements using the photodetectors 4, to illuminate the second emitters 3 and obtain a second set of measurements using the photodetectors 4, and to subtract the second set of measurements from the first set of measurements. The controller may be configured to multiply the second set of measurements by a weighting factor before subtracting the second set of measurements from the first set of measurements. Further details of the methods, processes and calculations carried out by the controller 27 are described hereinafter. Para. 0110.
The analytical test device 1 also includes at least one output device 28. For example, the output device 28 may take the form of one or more light emitting diodes which are arranged for viewing by a user of the analytical test device 1. The controller 27 may be configured to illuminate each light emitting diode in response to a concentration of a specific analyte vector exceeding a predetermined threshold. Para. 0111.
In another example, the at least one output device 28 may take the form of a wired or wireless communications interface for connection to a data processing apparatus (not shown). The data processing apparatus may take the form of, for example, a mobile telephone, tablet computer, laptop, desktop or a server. The controller may be configured to output the measured concentrations of one or more analytes to the data processing apparatus (not shown) via the wired or wireless communications interface. Para. 0113.
A signal obtained using the second light emitter(s) may be subtracted from a signal obtained using the first emitter(s) in order to compensate for optical scattering due to defects or other inhomogeneities in a medium, or substrate which forms part of the sample 9. The subtraction is carried out by the controller 27. Para. 0131.
Referring also to FIGS. 11 to 13, a process of obtaining and correcting absorbance measurements may be carried out by the controller 27 of the analytical test device 1. Para. 0147.
The conjugate portion 64 has been pre-treated with at least one particulate labelled binding reagent for binding an analyte which is being tested for, to form a labelled-particle-analyte complex. A particulate labelled binding reagent is typically, for example, a label particle 21 which has been sensitised to specifically bind to the analyte. The particles provide a detectable response, which is usually a visible optical response such as a particular colour, but may take other forms. For example, particles may be used which are visible in infrared, which fluoresce under ultraviolet light, or which are magnetic. Typically, the conjugate portion 64 will be treated with one type of particulate labelled binding reagent to test for the presence of one type of analyte in the liquid sample 72. However, lateral flow devices 62 may be produced which test for two or more analytes using two or more particulate labelled binding reagents concurrently. The conjugate portion 64 is typically made from fibrous glass, cellulose or surface modified polyester materials. Para. 0190
As the flow front 45 moves into the test portion 65, labelled-particle-analyte complexes and unbound label particles are carried along towards the second end 44. The test portion 65 includes one or more testing regions 20 and control regions 26 which are monitored by a corresponding light emitting diode array 60 and photodiode 4 pair. A testing region 20 is pre-treated with an immobilised binding reagent which specifically binds the label particle-target complex and which does not bind the unreacted label particles. As the labelled-particle-analyte complexes are bound in the testing region 20, the concentration of the label particles 21 in the testing region 20 increases. The concentration increase may be monitored by measuring the absorbance of the testing region 20 using the corresponding light emitting diode array 60 and photodiode 4. The absorbance of the testing region 20 may be measured once a set duration has expired since the liquid sample 72 was added. Alternatively, the absorbance of the testing region 20 may be measured continuously or at regular intervals as the lateral flow strip is developed. Para. 0191.
To provide distinction between a negative test and a test which has simply not functioned correctly, a control region 26 is often provided between the testing region 20 and the second end 44. The control region 26 is pre-treated with a second immobilised binding reagent which specifically binds unbound label particles and which does not bind the labelled-particle-analyte complexes. In this way, if the lateral flow testing device 62 has functioned correctly and the liquid sample 72 has passed through the conjugate portion 64 and test portion 65, the control region 26 will exhibit an increase in absorbance. The absorbance of the control region 26 may be measured by the second pair of a light emitting diode array 60 and a photodiode 4 in the same way as for the testing region 20. The test portion 65 is typically made from fibrous nitrocellulose, polyvinylidene fluoride, polyethersulfone (PES) or charge modified nylon materials. All of these materials are fibrous, and as such the sensitivity of the absorbance measurements may be improved by subtracting the measurements obtained using the second wavelength λ.sub.2 to correct for inhomogeneity of the porous strip 19 material. Para. 0192.
Although not shown in FIG. 28, the self-contained lateral flow testing device 62 also includes the controller 27, which is mounted in the base 67 or the lid 68. Para. 0194.
The first light emitter(s) 2 may be switched off for a period of duration δt.sub.0, so that the photodetector(s) 4 may measure fluorescence excited by the light 5 from the first light emitter(s) 2 (step S3). In a similar way, the so second light emitter(s) 3 may be switched off for a period of δt.sub.0, so that the photodetector(s) 4 may measure fluorescence excited by the light 6 from the second light emitter(s) 2 (step S5). This approach can be used to excite a first fluorescent marker using light 5 of the first wavelength λ.sub.1 and to excite a second fluorescent marker using light 6 of the second wavelength λ.sub.2. Para. 0212.
Concentrations of N−1 different analytes may be determined whilst correcting for inhomogeneity of a porous strip 19, or other such source of background scattering, by sequentially illuminating the sample receiving portion 8 using N different wavelengths. Each of the N wavelengths may be provided by a corresponding set of one or more light emitters. The controller 27 may illuminate each of the N sets of one or more light emitters according to a sequence, such that only one set of emitters is emitting light at any given time. Some of the N−1 analytes may not be of direct interest, for example, some of the N−1 analytes may be substances or compositions which provide the colouration of a sample. However, accounting for analytes providing coloration of a sample can allow more accurate detection and quantification of analytes of interest contained in the sample. Para. 0220.
Regarding Applicant’s claim 1, Roberts discloses an apparatus comprising:
a multi-modal diagnostic test reading apparatus (see abstract and para. 0002), comprising:
a diagnostic test assembly receiving component [see for example test strip received into test device (para. 0158); see for example test strip mounted in a sample mounting stage (para. 0178)];
at least one image sensor [see para. 0030 disclosing that the photodetectors may form an image sensor to image all or a portion of the sample receiving portion of the optical path; and see for example image sensor or camera in paras. 0160 and 0161; and see photodetectors as disclosed above];
a plurality of light sources [see light emitters, for example in paras. 0009, 0010, 0026, 0158, 0174, 0181 and implied elsewhere in the disclosures regarding illumination] having respective different spectral properties [para. 0181, 0220];
and a controller [paras. 0110, 0111, 0113, 0131, 0147, 0194 and 0220]; wherein the controller is configured to:
control operation of the light sources and the at least one image sensor to acquire a plurality of images, each of the acquired images representing at least a corresponding portion of the diagnostic test assembly as illuminated by a corresponding one of the light sources;
and(ii) process the acquired images to determine a diagnostic test result of the diagnostic test, the diagnostic test result being dependent upon the processed images representing illumination by respective ones of the light sources having respective different spectral properties.
Claim 3 recites the apparatus of claim 1, wherein the controller is configured to include an operating mode wherein the plurality of images include:
an absorption/reflection-based image of a first colorimetric signal produced at a first test region of the diagnostic test assembly;
and an absorption/reflection-based image of a second colorimetric signal produced at a second test region of the diagnostic test assembly;
wherein the spectral properties of the first colorimetric signal are different to the spectral properties of the second colorimetric signal.
See Roberts’ disclosures regarding a controller to perform the disclosed processes [paras. 0110, 0111, 0113, 0131, 0147, 0194 and 0220]. See Roberts’ disclosures regarding absorption or reflection detection ([paras. 0161, 0164, 0183, 0185, 0191-0192]. See also Roberts’ disclosures regarding detection of different analytes [para. 0220] and different wavelengths [para. 0192].
See also Roberts’ disclosure that when a lateral flow test strip 18 is received into an analytical test device 1, the image sensor 24 may be arranged to image one or more test regions 20 and the surrounding areas of the porous strip 19. A lateral flow test strip 18 may include one or more pairs 25, each pair 25 including a testing region 20 and a control region 26, and the image sensor 24 may be arranged to image the one or more pairs 25 at the same time. An image captured using the second, reference wavelength λ.sub.2 may be subtracted from an image captured using the first, measurement wavelength λ.sub.1, in order to compensate for background variance due to inhomogeneity of the fibres 22 making up the porous strip 19. The subtraction may be weighted using a weighting factor α when the absolute intensity of illumination from the first and second emitters 2, 3 is not substantially equal and/or when the sensitivity of the image sensor 24 differs between the first and second wavelengths λ.sub.1, λ.sub.2. Para. 0160.
Claim 7 recites the apparatus of claim 3, wherein the first and second test regions are first and second immunoassay capture lines of a lateral flow strip. See Roberts’ disclosure regarding a lateral flow strip and test lines in paragraph 0178, 0196 and 0200-0203.
Claim 8 recites the apparatus of claim 1, wherein the controller is configured to include an operating mode wherein the plurality of images include:
an absorption/reflection-based image of a modified sample contained within a diagnostic test assembly, relating to a first property of the sample;
and multiple fluorescence-based images of a fluorescent signal produced by the modified sample relating to a second property of the sample.
See Roberts’ disclosures regarding absorption or reflection detection [paras. 0161, 0164, 0183, 0185, 0191-0192].
See Roberts’ disclosures regarding fluorescence detection [paras. 0190, 0212].
See Roberts’ disclosure regarding an image captured using the second, reference wavelength λ.sub.2 may be subtracted from an image captured using the first, measurement wavelength λ.sub.1, in order to compensate for background variance due to inhomogeneity of the fibres 22 making up the porous strip 19. Para. 0160.
Claim 10 recites the apparatus of claim 1, wherein the controller is configured to include an operating mode wherein the plurality of images include:
a first, absorption/reflection-based image of one or more visual features within a test area of the diagnostic test assembly; and a second image of at least a signal produced at a test region of the diagnostic test assembly,
the second image being an image of either: a fluorescent signal; or a colorimetric signal; wherein the diagnostic test result is dependent upon the one or more visual features and the signal of the processed images.
See Roberts’ disclosures regarding absorption or reflection detection [paras. 0161, 0164, 0183, 0185, 0191-0192].
See Roberts’ disclosures regarding fluorescence detection [paras. 0190, 0212].
See Roberts’ disclosure regarding an image captured using the second, reference wavelength λ.sub.2 may be subtracted from an image captured using the first, measurement wavelength λ.sub.1, in order to compensate for background variance due to inhomogeneity of the fibres 22 making up the porous strip 19. Para. 0160.
Claim 11 recites the apparatus of claim 10, wherein the one or more visual features comprise one or more of:
flow of a coloured sample through a fluidic test cartridge;
flow of a coloured sample along a lateral flow strip;
wetting of a lateral flow strip due to flow of a transparent sample;
variation in illumination;
background staining on a lateral flow strip;
dirt, dust, or imperfections of a lateral flow strip;
and reflections from a reflective surface of the viewing window.
See Roberts’ disclosures regarding an image captured using the second, reference wavelength λ.sub.2 may be subtracted from an image captured using the first, measurement wavelength λ.sub.1, in order to compensate for background variance due to inhomogeneity of the fibres 22 making up the porous strip 19. Para. 0160.
Claim 12 recites the apparatus of claim 11 wherein:
the one or more visual features comprise background staining and variation in illumination level; and the controller is configured to subtract the first image from the second image to produce a third image with reduced contribution from the background staining or variation in illumination level, wherein the third image is used to determine the diagnostic test result.
See Roberts’ disclosure of an image captured using the second, reference wavelength λ.sub.2 may be subtracted from an image captured using the first, measurement wavelength λ.sub.1, in order to compensate for background variance due to inhomogeneity of the fibres 22 making up the porous strip 19. The subtraction may be weighted using a weighting factor α when the absolute intensity of illumination from the first and second emitters 2, 3 is not substantially equal and/or when the sensitivity of the image sensor 24 differs between the first and second wavelengths λ.sub.1, λ.sub.2. Para. 0160. [Examiner notes that it is understood that the subtraction between the images result in a third image.]
Claim 15 recites the apparatus of claim 1, further comprising one or more optical diffusers positioned between one or more of the light sources and a diagnostic test assembly received in the apparatus to improve illumination of the diagnostic test assembly.
See Roberts’ disclosure of a diffuser in paragraphs 0161, 0170, 0180 and 0188.
Claim 16 recites the apparatus of claim 1, wherein the controller is configured to automatically determine one or more operating modes for acquiring the plurality of images, and to control operation of the light sources and the at least one image sensor in accordance with the determined one or more operating modes to acquire the plurality of images.
See Roberts’s disclosures regarding a controller to perform the disclosed processes [also discussed above] in paragraphs 0110, 0111, 0113, 0131, 0147, 0190, 0191, 0192, 0194, 0212 and 0220.
Claim 17 recites the apparatus of claim 1, wherein the controller is configured:
(a) to control operation of the light sources and the at least one image sensor to acquire at least one image of the plurality of images;
(b) to process the at least one image to determine one or more operating modes for acquiring one or more other images of the plurality of images;
and (c) to control operation of the light sources and the at least one image sensor in accordance with the determined one or more operating modes to acquire the one or more other images of the plurality of images.
See Roberts’s disclosures regarding a controller to perform the disclosed processes [also discussed above] in paragraphs 0110, 0111, 0113, 0131, 0147, 0190, 0191, 0192, 0194, 0212 and 0220.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 2 and 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 20190226985 (hereinafter “Roberts”).
Applicant’s claim 2 recites the apparatus of claim 1, further comprising an optical filtering component operable by the controller to selectably locate a corresponding optical filter of one or more optical filters between the image sensor and the diagnostic test assembly to filter corresponding wavelengths from the image sensor when acquiring one or more corresponding images of the acquired images.
Roberts, discussed further above, discloses that the analytical test device may include a simplified optical path which does not require optical components such as filters or monochromators to perform dual-wavelength measurements. Thus, the analytical test device may be less bulky and simpler to manufacture. Para. 0012.
However, it would have been obvious to one skilled in the art that while Roberts discloses that filters are not required, filters, as well-known optical components in the art, may be utilized with minor, obvious modification such as in size and shape of the device disclosed by Roberts to accommodate filters.
Claim 5 recites the apparatus of claim 1, wherein the controller is configured to include an operating mode wherein the plurality of images include:
an absorption/reflection-based image of a colorimetric signal produced at a first test region of the diagnostic test assembly;
and a fluorescence-based image of a fluorescent signal produced at a second test region of the diagnostic test assembly.
See Roberts’ disclosures regarding absorption or reflection detection [paras. 0161, 0164, 0183, 0185, 0191-0192].
See Roberts’ disclosure regarding an image captured using the second, reference wavelength λ.sub.2 may be subtracted from an image captured using the first, measurement wavelength λ.sub.1, in order to compensate for background variance due to inhomogeneity of the fibres 22 making up the porous strip 19. Para. 0160.
See Roberts’ disclosures regarding fluorescence detection [paras. 0190, 0212].
See Roberts’ disclosure regarding measuring gold nanoparticle in test lines [para. 0196].
The wavelengths corresponding to each set of light emitters may be selected in dependence upon the absorbance spectrum of one or more target analytes. The wavelength corresponding to each set of light emitters may be selected such that a target analyte has relatively higher absorbance at said wavelength than at a wavelength corresponding to each other set of light emitters. A target analyte may be any suitable labelling molecule or particles such as, for example, gold nanoparticles. Para. 0022.
The first and second wavelengths may be selected in dependence upon the absorbance spectrum of a target analyte. The first and second wavelengths may be selected such that a target analyte has relatively higher absorbance at the first wavelength than at the second wavelength. The ratio of target analyte absorbance at the first and second wavelengths may be at least two, up to an including five, up to an including ten or more than ten. A target analyte may be any suitable labelling molecule or particles such as, for example, gold nanoparticles. Para. 0023.
Roberts discloses use of fluorescence detection and gold nanoparticles detection, though it is not clear if Roberts teaches that both alternatives are provided in the same device. It would have been obvious to one skilled in the art to provide both known labelling techniques in the same apparatus as may be desirable since it is known, as shown by Roberts, that either labelling method can be used.
Claim(s) 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 20190226985 (hereinafter “Roberts”) in view of US 20180306709 (hereinafter “Zaccari”).
Claim 4 recites the apparatus of claim 1, wherein the image sensor includes a Bayer filter, and while acquiring respective images of the plurality of images, the controller is configured to selectively use only respective different subsets of pixels of the image sensor selected from three subsets of pixels of the image sensor with red, blue and green Bayer filter elements, respectively.
Roberts, discussed further above, including a controller for performing the disclosed processes, is silent as to a Bayer filter and use of the controller for selectively using pixels as recited.
However a Bayer filter and its use is known in the art, as shown by Zaccari, and modification to configure the Roberts’ controller to control the image sensor as recited would have been obvious to one skilled in the art in order to use such known elements in a familiar manner.
More specifically, Zaccari discloses a first filter mosaic 27 for an image sensor 2. Para. 0114.
An image sensor 2 having multiple different colour channels may be provided using a filter mosaic 27 overlying an array of light sensors. Each such light sensor is sensitive to the wavelengths of light which are transmitted by the overlying filter. The first filter mosaic is a Bayer filter (or RGBG filter) for a red-green-blue, or RGB image sensor 2. Only four repeating units of the first filter mosaic are shown in FIG. 5A. RGB image sensors 2 are the most commonly employed image sensors 2 used in digital cameras, smart phones and so forth. Alternative mosaics of R, G and B filters may be used. Para. 0115.
Referring also to FIG. 5B, a second filter mosaic 28 for an image sensor 2 is shown. Para. 0116.
Although RGB image sensors 2 are commonly employed, other types of image sensors 2 are possible which use alternative colour channels. For example, the alternative cyan (C), yellow (Y), magenta (M) colour scheme may be used instead of an RGB colour scheme. The second filter mosaic 28 is a CYYM filter mosaic for a CYM image sensor 2. Para. 0117.
Referring also to FIG. 5C, a third filter mosaic 29 for an image sensor 2 is shown. Para. 0118.
Image sensors 2 are not restricted to only three colour channels, and a greater number of colour channels may be included. The third filter mosaic 29 includes R, G and B filters, and additionally includes infrared (IR) filters. An infrared colour channel for an image sensor will typically transmit near infrared (NIR) light. Including a colour channel for IR/NIR can be useful for the methods of the present specification. In particular, materials which are different (visible) colours may often have very similar reflectance/transmittance at IR/NIR wavelengths. The third mosaic filter 29 is an RGBIR mosaic filter for an RGBIR image sensor 2. Para. 0119.
Referring also to FIG. 5d, a fourth filter mosaic 30 for an image sensor 2 is shown. Para. 0120.
Image sensors 2 are not restricted to three visible colour channels. Some image sensors 2 may use filter mosaics which combine four different visible colour channels, for example, the fourth filter mosaic 30 is a CYGM filter mosaic for a CYGM image sensor 2. Para. 0121.
An image sensor 2 may include non-visible colour channels other than IR/NIR, for example an image sensor 2 may include an ultraviolet colour channel. Para. 0122.
The mobile device 49 includes one or more processors. The step of extracting the first and second mono-colour arrays L.sup.1, L.sup.2 or images I.sup.1, I.sup.2 (step S2 in FIG. 14) may be carried out by the one or more processors. The step of determining the filtered array or image based on the first and second mono-colour arrays (step S3 in FIG. 14) may be carried out by the one or more processors (not shown) of the mobile device 49. Para. 0167.
If the computing power of the mobile device 49 is sufficient, a preview image displayed on the display 51 may show filtered images I.sup.F instead of the initial, unprocessed sample image I.sup.S before the camera of the mobile device 49 is activated to obtain an image. This may help a user to arrange the mobile device 49 in the right position with respect to the lateral flow device 10. Para. 0168.
In this way, the mobile device 49 may be used to perform qualitative colorimetric analysis of the lateral flow device 10 with an improved limit of detection provided by use of the filtered array or image. Para. 0169.
Thus a Bayer filter (or RGBG filter) for a red-green-blue, or RGB image sensor, is known in the art, as shown by Zaccari, and modification to configure the Roberts’ controller to control the image sensor as recited would have been obvious to one skilled in the art in order to use such known elements in a familiar manner.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over US 20190226985 (hereinafter “Roberts”), as applied to claim 5 above, in view of US 20160349251 (hereinafter “Hao”).
Claim 6 recites the apparatus of claim 5, wherein: the colorimetric signal is a signal produced by colloidal gold labelled particles; and the fluorescent signal is a signal produced by europium chelate fluorescence labeled particles.
Roberts has been discussed above (see discussion of claims 1 and 5).
However, regarding claim 6, Roberts is silent as to europium chelate being the fluorescence labeled particles. However, such fluorescence particles are known in the art for use as labels, as shown by Hao.
Hao teaches that fluorescent europium chelates are known to exhibit large Stokes shifts (˜290 nm) with no overlap between the excitation and emission spectra and very narrow (10-nm bandwidth) emission spectra at 615 nm. In addition, the long fluorescence lifetimes (measurable in microseconds instead of the nanosecond lifetimes measurable for conventional fluorophores) of the chelates help filter out noise and other interference having a low fluorescent lifetime. The long fluorescent lifetimes thus permit use of the chelates for microsecond time-resolved fluorescence measurements, which further reduce the observed background signals. Additional advantages of using europium chelates include that europium chelates are not quenched by oxygen. Para. 0015.
The fluorescent labels (such as europium chelates) can be conjugated to the antibody using conventional techniques in immunology. Fluorescence can be quantified using a fluorimeter or UV/vis spectrophotometer using the known extinction coefficient of the fluorescent label. Para. 0095.
While Roberts is silent as to europium chelate being the fluorescence labeled particles, such fluorescence particles are known in the art for use as labels, as shown by Hao. Providing europium chelate as the fluorescent label in the Roberts invention would have been obvious to one skilled in the art as a known fluorescent label alternative, with advantages such as disclosed by Hao.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over US 20190226985 (hereinafter “Roberts”) in view of US 20190357827 (hereinafter “Li”).
Roberts has been discussed above (see discussion of claims 1 and 8 above).
However, Roberts does not disclose the limitations of Applicant’s claim 9, which recites the apparatus of claim 8, wherein: the modified sample is blood mixed with a buffer solution; the first sample property is an amount of haemoglobin in the sample; the second sample property is an amount of nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) produced while running the test;wherein the controller is configured to determine, based on changes in the multiple fluorescence-based images over time, an amount of glucose-6-phosphate dehydrogenase (G6PD) present in the sample; and wherein determining the test result comprises calculating the amount of G6PD relative to the amount of haemoglobin in the sample.
However, these are known analytes tested and studied in the art, as shown by Li (para.0289). Modification of the Roberts invention to test for these analytes requires routine skills in the art given that such analysis and the required reagents for such analysis are known in the art.
Claims 13, 14 and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 20190226985 (hereinafter “Roberts”) in view of US 20180100869 (hereinafter “Niemeyer”).
Roberts has been discussed above.
Applicant’s claim 13 recites the apparatus of claim 1, wherein the controller is configured to include an operating mode wherein the plurality of images include one or more absorption/reflection-based images of one or more features of the diagnostic test assembly, the diagnostic test result being dependent upon the one or more visual features,
and wherein the one or more features comprise one or more of:
the outline of the diagnostic test assembly;
a viewing window of the diagnostic test assembly;
a data code printed or etched on the diagnostic test assembly;
and a label of or affixed to the diagnostic test assembly.
Roberts discloses the limitations above (see further above) with exception of a data code printed or etched on the diagnostic test assembly, and a label of or affixed to the diagnostic test assembly.
See for example Roberts’ disclosure regarding a lateral flow test strip mounted in a sample mounting stage including a window for transmission measurements, or alternatively a lateral flow test strip mounted fixedly with respect to the analytical test device. Para. 0178.
However, Roberts is silent as to a data code on the analytical test device.
Niemeyer however discloses the following.
Niemeyer discloses an analysis system that comprises an analysis device and a cartridge for testing the sample, the cartridge preferably being designed for receiving the sample. The analysis device is designed to receive the cartridge or to connect said cartridge electrically, thermally and/or pneumatically. The analysis device is preferably designed to subsequently carry out the test using the received cartridge. The cartridge can be inserted or loaded into the analysis device, whereupon the analysis device can act on the cartridge in order to carry out the test. Para. 0023.
Niemeyer discloses retrieving control information 510, calibration information 520 and/or evaluation information 530 from the database 500 independently, disconnected or separately from the analysis device 200, preferably by optically reading out the cartridge identifier 100C from the cartridge 100. Alternatively or additionally, a memory means 100D of the cartridge 100 that can be read out electronically makes it possible for the cartridge identifier 100C to be read out without there being an optical connection to or visual contact with the cartridge 100, for example when said cartridge is inserted into the analysis device 200. Para. 0265.
The respective cartridges 100 are preferably identified at least twice or cartridge identifier 100C is read out and used at least twice, namely preferably once directly by the operating instrument 400 in order to retrieve control information 510 and/or calibration
information 520 and/or evaluation information 530 and a second time by means of or via the analysis device 200 in order to ensure that the test is carried out using control information 510,
calibration information 520 and/or evaluation information 530 that corresponds to the cartridge 100 and/or in order to ensure and/or verify that the control information 510, calibration information 520 and/or evaluation information 530 corresponds to the cartridge 100. Para. 0267.
The memory device of the cartridge as described by Niemeyer is equivalent to Applicant’s data code as well as label on the analysis device [or alternatively the cartridge identifier is equivalent to Applicant’s label]. It would have been obvious to one skilled in the art to provide in the Roberts’ device a memory device, as taught by Niemeyer, in order to ensure that the test is carried out using control information, calibration information and/or evaluation information that corresponds to the cartridge and/or in order to ensure and/or verify that the control information, calibration information and/or evaluation information corresponds to the cartridge. Para. 0267.
Applicant’s claim 14 recites the apparatus of claim 13, wherein:
the one or more features comprise the data code,
the controller is configured to obtain information from the data code;
and the controller processes the information obtained from the data code to determine parameters including a test identifier,
wherein one or more of the parameters are used to determine the diagnostic test result, and are displayed together with the diagnostic test result.
The memory device of the cartridge as described by Niemeyer is equivalent to Applicant’s data code. It would have been obvious to one skilled in the art to provide in the Roberts’ device a memory device, as taught by Niemeyer, in order to ensure that the test is carried out using control information, calibration information and/or evaluation information that corresponds to the cartridge and/or in order to ensure and/or verify that the control information, calibration information and/or evaluation information corresponds to the cartridge. Para. 0267.
Claim 18 recites the apparatus of claim 17, wherein the at least one image includes at least one absorption/reflection-based image of one or more of:
an outline of the diagnostic test assembly;
a data code printed on or etched into the diagnostic test assembly;
and a label of or affixed to the diagnostic test assembly;
wherein the controller is configured to determine an operating mode for acquiring at least one of the one or more other image by processing the at least one image to determine at least one of:
a type of the diagnostic test assembly represented in the image;
and a type of the diagnostic test of the diagnostic test assembly.
The memory device of the cartridge as described by Niemeyer is equivalent to Applicant’s data code and Neimeyer’s cartridge identifier is equivalent to Applicant’s test identifier. It would have been obvious to one skilled in the art to provide in the Roberts’ device a memory device and cartridge identifier, as taught by Niemeyer, in order to ensure that the test is carried out using control information, calibration information and/or evaluation information that corresponds to the cartridge and/or in order to ensure and/or verify that the control information, calibration information and/or evaluation information corresponds to the cartridge. Para. 0267.
Conclusion
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/Ann Montgomery/Primary Examiner, Art Unit 1678
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