Polynucleotide Conjugates for Multiplexed Antibody Detection

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Solution Overview

Problem

Current methods for analyte detection, such as DNA microarrays and peptide or protein arrays, face challenges including high background noise, limited dynamic range, and difficulty in manufacturing and screening, particularly in detecting specific antibodies or antigens in biological samples.

Innovation Solution

The development of polypeptide-polynucleotide conjugates, which comprise a polypeptide with an epitope for specific binding and a polynucleotide with identifying, engaging, and optional primer sequences, allowing for specific binding and analysis of antibodies or antigens through hybridization and sequencing, enabling sensitive detection and multiplexed assays.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If DNA microarrays are used for comprehensive gene expression analysis, then the ability to study labeled molecules is improved, but background noise increases and dynamic range decreases due to non-specific hybridization

Engineering Contradiction:

Improveability to study labeled moleculesVSAvoidbackground noise and dynamic range

Core Design Contradiction:

Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent introduces a polynucleotide conjugate as an intermediary component that bridges the analyte binding element and the detection element. This conjugate comprises a polynucleotide sequence that specifically hybridizes to the analyte while carrying a detectable label, thereby mediating the interaction between the analyte and detection system to reduce non-specific binding and improve signal-to-noise ratio

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies the detection parameters by using polynucleotide-based detection instead of traditional fluorescent labeling. The detection sensitivity is enhanced through PCR amplification of the polynucleotide conjugate, transforming the detection mechanism to achieve lower background noise and extended dynamic range while maintaining the ability to study multiple labeled molecules

Inventive Principle:

Principle #35Parameter changes

2Productivity

If peptide or protein arrays are used for high-throughput screening, then the screening capability is improved, but manufacturing difficulty increases and the number of labeled molecules that can be screened simultaneously is limited

Engineering Contradiction:

Improvehigh-throughput screening capabilityVSAvoidmanufacturing difficulty

Core Design Contradiction:

ProductivityVSEase of manufacture

Solution Approach 1:

The patent segments the detection system into separate functional components: analyte binding elements, polynucleotide conjugates, and detection probes. This segmentation allows for independent optimization of each component and simplifies manufacturing, as each element can be produced and quality-controlled separately before assembly in the final assay

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The polynucleotide conjugate serves multiple functions simultaneously: it acts as an analyte binder, a carrier for the detectable label, and a template for PCR amplification. This multi-functionality reduces the number of separate components needed, simplifying manufacturing while enabling high-throughput screening of multiple analytes in parallel

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Reliability

If traditional immunoassays are used for antibody detection, then specificity is improved, but sensitivity and dynamic range are limited

Engineering Contradiction:

ImprovespecificityVSAvoidsensitivity and dynamic range

Core Design Contradiction:

ReliabilityVSMeasurement precision

Solution Approach 1:

The patent employs PCR amplification to create multiple copies of the polynucleotide conjugate bound to the analyte. This copying mechanism dramatically increases the signal intensity and extends the dynamic range of detection while maintaining specificity, as the amplification process faithfully replicates the original conjugate sequence without introducing non-specific signals

Inventive Principle:

Principle #26Copying

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach enhances the sensitivity and dynamic range of analyte detection, reduces background noise, and allows for the analysis of multiple analytes simultaneously, improving the ability to detect specific antibodies or antigens in complex biological samples.

Implementation Method 1

a first polynucleotide comprising a first identifying sequence that identifies the first polypeptide, a first engaging sequence

Methodology Applied

Scientific EffectHybridization:

Data Source

PatentUS10288608B2Polynucleotide conjugates and methods for analyte detection

Publication Date: 2019.05.14 PROGNOSYS BIOSCIENCES INC

AI summary

The present disclosure provides polynucleotide conjugates, methods, and assay systems for use in detecting the presence, absence, and/or amount of an analyte in a sample. Various polynucleotide conjugates, conjugate pairs, sets, libraries, and assay systems comprising the same are disclosed. In particular, methods and assay systems for antibody detection and analysis are provided. For example, assays capable of high levels of multiplexing are used for antibody detection and analysis in a biological sample, e.g., Lyme disease patient samples. The presently disclosed polynucleotide conjugates, methods, and assay systems can be used to provide sensitive and reliable diagnosis, even at early stages of a disease or condition. Use for monitoring disease progression and prognosis is also disclosed.