Virus Sample Quality Measurement Using Dynamic DNA Extinction Coefficients

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current technologies for measuring quality attributes of virus samples, such as adeno-associated virus (AAV), face challenges due to the lack of accurate encapsulated DNA extinction coefficients, which vary with DNA length and are not well known, leading to inaccurate measurements when assuming a 100% full AAV sample is not available.

Innovation Solution

A computer-implemented method and system that receives light scattering, differential refractive index, and ultraviolet absorbance data, calculates protein fraction and DNA extinction coefficient using known molecular weights and refractive index increments, and determines quality attribute values based on these calculations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If current technologies assume a 100% full AAV sample, then the measurement process is simplified, but the measurement precision deteriorates because the encapsulated DNA extinction coefficients are not well known and vary with DNA length

Engineering Contradiction:

Improvemeasurement process simplicityVSAvoidDNA extinction coefficient accuracy

Core Design Contradiction:

Ease of operationVSMeasurement precision

Solution Approach 1:

The patent changes the approach from assuming fixed extinction coefficients to dynamically calculating them based on measured protein fractions and multiple detection signals (light scattering, dRI, UV absorbance). This parameter transformation resolves the contradiction by making the measurement process more complex but achieving accurate DNA extinction coefficients that account for varying DNA lengths

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent replaces the simple assumption-based calculation method with a multi-detector system that uses light scattering data, differential refractive index data, and UV absorbance data to computationally determine DNA extinction coefficients. This substitution of measurement mechanics achieves both accuracy and operational feasibility

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If multiple detection methods (light scattering, dRI, UV absorbance) are used to calculate DNA extinction coefficients, then measurement precision improves, but device complexity increases

Engineering Contradiction:

ImproveDNA extinction coefficient accuracyVSAvoidmulti-detector system complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent employs a multi-functional detection system where light scattering, dRI, and UV absorbance detectors work together to provide complementary information for calculating DNA extinction coefficients. Each detector serves multiple purposes: characterizing virus particles, measuring concentration, and determining protein fractions, thereby justifying the increased device complexity through enhanced measurement capabilities

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent uses protein fraction calculations as an intermediary that connects the multiple detection methods to the final DNA extinction coefficient determination. This intermediary computational step integrates data from all detectors and translates them into accurate DNA extinction coefficients, managing the complexity through systematic data processing

Inventive Principle:

Principle #24Intermediary (Mediator)

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

Enables accurate measurement of DNA extinction coefficients at 260 and 280 nm, improving the precision of AAV quality attribute assessments.

Implementation Method 1

receiving, by a computer system, light scattering data from a light scattering detector analyzing separations of a virus sample

Methodology Applied

Scientific EffectLight scattering: Scattering

Implementation Method 2

differential refractive index (dRI) data from a differential refractometer analyzing the separations

Methodology Applied

Scientific EffectDifferential refractive index: Refraction

Implementation Method 3

ultraviolet (UV) absorbance data, A, from a UV detector at at least one wavelength analyzing the separations

Methodology Applied

Scientific EffectUV absorbance: Absorption (EM radiation)

Data Source

PatentUS12385819B2Measuring quality attributes of a virus sample

Publication Date: 2025.08.12 WYATT TECHNOLOGY CORP

AI summary

The present disclosure describes a computer implemented method, a system, and a computer program product of measuring quality attributes of a virus sample. In an embodiment, the method, system, and computer program product include (1) receiving light scattering (LS) data from a light scattering detector analyzing separations of a virus sample, dRI data, and UV data, (2) receiving a molecular weight of a protein component of the sample, Mprotein (expected), a refractive index increment of the protein component, (dn/dc)protein, a refractive index increment of a DNA component of the sample, (dn/dc)DNA, and an extinction coefficient of the protein component, εprotein, (3) calculating a protein fraction of the sample, xprotein, with respect to the LS data, the dRI data, the Mprotein (expected), the (dn/dc)protein, the (dn/dc)DNA, and an optical constant, K, (4) calculating a DNA extinction coefficient of the sample, εDNA, and (5) calculating quality attribute values of the sample.