Self-verifying diagnostic architecture with intrinsic authentication and environmental history recording

Abstract

A verification system comprises a substrate carrying a recognition layer configured to undergo a target-dependent structural change upon binding of a target molecule; a first transducer configured to

Claims

905.6Self-Verifying Diagnostic Architecture with Intrinsic Authentication and Environmental History RecordingAMENDED CLAIMSClaim 1.A diagnostic test device for detecting a target analyte in a biological sample, comprising:a substrate defining a fluidic path;a biorecognition element configured to selectively bind the target analyte, thereby undergoing a target-dependent structural change;a first transducer configured to generate a first verification signal in response to the structural change via a first physical transduction mechanism;a second transducer configured to generate a second verification signal in response to the same structural change via a second physical transduction mechanism that is mechanistically distinct from the first physical transduction mechanism, such that any single failure mode that eliminates the first verification signal does not eliminate the second verification signal;a comparator configured to derive a comparison value characterising the degree of agreement between the first and second verification signals; anda decision module configured to release a diagnostic result only when the comparison value satisfies a predetermined agreement condition, and to generate an invalid-test indication otherwise.14 05 26Claim 2.A diagnostic testing system for detecting a target analyte in a biological sample, comprising:a first test device comprising a first substrate carrying a first recognition layer and a first transducer configured to generate a first verification signal via a first physical transduction mechanism upon binding of the target analyte;a second test device comprising a second substrate separate from the first substrate, the second test device carrying a second recognition layer and a second transducer configured to generate a second verification signal via a second physical transduction mechanism upon binding of the target analyte, the second physical transduction mechanism being mechanistically distinct from the first physical transduction mechanism, such that any single failure mode that eliminates the first verification signal does not eliminate the second verification signal;a comparator configured to derive a comparison value characterising the degree of agreement between the first and second verification signals; anda decision module configured to release a diagnostic result only when the comparison value satisfies a predetermined agreement condition, and to generate an invalid-test indication otherwise.Claim 3.A method of performing a self-verifying diagnostic test for a target analyte in a biological sample, comprising:(a) contacting the biological sample with a first transducer to generate a first verification signal via a first physical transduction mechanism and with a second transducer to generate a second verification signal via a second, mechanistically distinct physical transduction mechanism, the first and second transducers being carried on a common substrate or on separate substrates;(b) deriving a comparison value characterising the degree of agreement between the first and second verification signals;(c) releasing a diagnostic result only when the comparison value satisfies a predetermined agreement condition; and14 05 26(d) generating an invalid-test indication when the agreement condition is not satisfied.Claim 4.A readout apparatus for use with a device according to claim 1 or a system according to claim 2, the readout apparatus comprising:a first measurement circuit configured to measure the first verification signal;a second measurement circuit configured to measure the second verification signal, operating on a different physical principle from the first measurement circuit;a processor configured to execute the comparator and the decision module; and an output interface configured to display a diagnostic result or an invalid-test indication.Claim 5.Use of the device of claim 1 or the system of claim 2 for point-of-care in vitro diagnosis of a medical condition in a subject, wherein a valid diagnostic result is released only when the comparison value satisfies the predetermined agreement condition such that a device presenting discordant signals cannot produce a reportable diagnostic result.Claim 6.The device of claim 1 or the system of claim 2, configured such that degradation or failure of one transducer does not prevent generation of a signal by the other transducer, and such that the degraded or failed state is detectable as a divergence in the comparison value exceeding a predetermined threshold, causing the decision module to output an invalid-test indication rather than a diagnostic result.Claim 7.The device of claim 1 or the system of claim 2, wherein the first physical transduction mechanism comprises a change in bulk electrical resistance or impedance arising from alteration of inter-particle spacing within a composite material comprising conductive particles dispersed in an insulating matrix.14 05 26Claim 8.The device or system of claim 7, wherein the conductive particles are dispersed in the insulating matrix at a concentration proximal to a percolation threshold, such that the structural change produces a discrete threshold-type change in bulk electrical resistance sufficient for unambiguous binary classification of analyte concentration.Claim 9.The device or system of claim 7 or claim 8, wherein the insulating matrix is a stimuli-responsive polymer and the conductive particles are selected from carbon nanotubes, graphene, reduced graphene oxide, carbon black, gold nanoparticles, or silver nanowires.Claim 10.The device of claim 1 or the system of claim 2, wherein the second physical transduction mechanism comprises molecular absorption or colourimetric change, fluorescence emission, plasmonic absorption or scattering, or chemiluminescence or bioluminescence.Claim 11.The device of claim 1 or the system of claim 2, wherein the biorecognition element is physically separated from but functionally coupled to the first transducer, enabling independent optimisation of binding specificity and signal magnitude.Claim 12.The device of claim 1 or the system of claim 2, wherein the comparator is configured to classify each verification signal into one of three states comprising POSITIVE, NEGATIVE and INDETERMINATE based on comparison with upper and lower threshold values, and to generate an invalid-test indication if either signal falls within the INDETERMINATE state.14 05 26Claim 13.The device of claim 1 or the system of claim 2, wherein the comparator is configured to monitor temporal evolution of each verification signal at a plurality of time points during an assay, to fit a kinetic model to each signal evolution, and to derive the comparison value based on comparison of kinetic parameters between the first and second verification signals.Claim 14.The device of claim 1 or the system of claim 2, wherein the fluidic path comprises a lateral flow path.Claim 15.The device of claim 1 or the system of claim 2, wherein the target analyte is selected from cardiac markers, inflammatory markers, infectious disease antigens or antibodies, hormones, cancer biomarkers, coagulation markers, drugs of abuse, therapeutic drugs, food safety analytes, environmental analytes, or veterinary analytes.Claim 16.The device of claim 1 or the system of claim 2, further comprising an authentication layer deposited on the substrate of at least one of the test devices, the authentication layer comprising luminescent material arranged in a spatially random manner so as to form a physically unclonable function configured to undergo progressive, irreversible stochastic degradation in response to environmental exposure, thereby generating a spatially unique degradation pattern having boundary morphology characteristic of intrinsic stochastic degradation processes and not reproducible by deterministic printing or lithographic processes;wherein the decision module is further configured to release a diagnostic result only when both:(a) the comparison value satisfies the predetermined agreement condition; and(b) a feature vector extracted from an image of the authentication layer matches an enrolled reference captured at manufacture within a predetermined authenticity14 05 26threshold and exhibits a fractal dimension characteristic of stochastic degradation rather than deterministic printing;and to generate an invalid-test indication when either condition is not satisfied.Claim 17.The device or system of claim 16, wherein the authentication layer comprises quantum dots with spatially varying shell thickness, including a stable reference zone incorporating thick-shell quantum dots exhibiting substantially unchanged fluorescence over the intended storage period, and a labile zone incorporating thin-shell quantum dots configured to undergo progressive irreversible degradation producing the fractal degradation pattern.Claim 18.The device or system of claim 16 or claim 17, wherein the decision module is further configured to estimate cumulative environmental exposure of the device from the observed extent of degradation of the authentication layer using a kinetic degradation model, and to withhold the diagnostic result if the estimated cumulative exposure is inconsistent with declared storage conditions.Claim 19.A readout apparatus according to claim 4, further comprising an optical imaging module configured to capture an image of the authentication layer of a device according to claim 16 and to extract therefrom a feature vector for comparison against the enrolled reference.Claim 20.A method of manufacturing a diagnostic test device according to claim 1, comprising:printing conductive electrodes on a substrate;depositing a stimuli-responsive percolation composite proximal to its percolation threshold over the electrodes to form the first transducer;14 05 26immobilising a biorecognition element at a test zone of a fluidic path defined on the substrate, the biorecognition element being physically separated from but functionally coupled to the first transducer;depositing a visual indicator to form the second transducer operating via a mechanistically distinct physical transduction mechanism; andassembling lateral flow components to form the fluidic path.Claim 21.The method of claim 20, further comprising:depositing an authentication layer on the substrate, the authentication layer comprising luminescent material arranged in a spatially random manner so as to form a physically unclonable function configured to undergo progressive, irreversible stochastic degradation; andimaging the authentication layer at manufacture to capture an enrolled reference.Claim 22.A non-transitory computer-readable medium comprising instructions which, when executed by a processor in a readout apparatus, cause the readout apparatus to:receive a first verification signal and a second verification signal arising from mechanistically distinct physical transduction mechanisms, such that any single failure mode affecting one signal does not affect the other;derive a comparison value characterising the degree of agreement between the signals;determine whether the comparison value satisfies a predetermined agreement condition; andoutput a diagnostic result only when the agreement condition is satisfied, otherwise output an invalid-test indication.Claim 23.The computer-readable medium of claim 22, further comprising instructions to:extract from an image of an authentication layer a feature vector comprising at least a fractal dimension;compare the feature vector against an enrolled reference; andoutput a diagnostic result only when both the agreement condition and the authenticity condition are satisfied, otherwise output an invalid-test indication.Claim 24.The device of claim 1, wherein the first transducer comprises interdigitated electrodes beneath a percolation composite amplification layer and contact pads at the device edge for external electrical readout.Claim 25.CXIThe device of claim 1 or the system of claim 2 when dependent on claim 16, wherein theluminescent material of the authentication layer comprises semiconductor quantum dots or non-quantum-dot luminophores.T +44(0)30 0300 2000Search report under Section 17 of the Patents Act 1977Application No.: GB2604905.6Claims searched: 1 to 21,24 and 25Date search completed: 11 May 2026International classificationSubclass and subgroup Valid from G01N33 / 543 01 / 01 / 2006Field of searchWorldwide search of patent documents classified in the following areas of the IPC: G01NDatabases used in the preparation of this search report:SEARCH-NPL; SEARCH-PATENTDocuments considered to be relevantPatent literatureCategory Relevant to claims Document of relevance A - US 2020 / 0041497 A1 (CASS et al.) - See especially paragraphs [0074] to [0076] and figure 9B. A - US 2009 / 0113980 A1 (HIRAI et al.) - See especially paragraphs [0001] to [0006].{clm:-Non-patent literature[None]CategoriesLetter or symbol DescriptionT +44(0)30 0300 2000Letter or symbol Description X Document indicating lack of novelty or inventive step. Y Document indicating lack of inventive step, if combined with another document of the same category. & Member of the same patent family. A Document indicating technological background. P Document published on or after the priority date but before the filing date of the present application. E Earlier application published on or after the filing date of the present application.

Images