Newborn Screening Using Immuno-SRM for Low-Abundance Disease Peptides
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Solution Overview
Problem
Current newborn screening methods are inadequate for detecting primary immunodeficiencies, cystinosis, and Wilson disease, as they lack reliable, cost-effective assays to identify low-abundance markers associated with these disorders, often leading to irreversible damage or fatality by the time symptoms emerge.
Innovation Solution
Development of multiplexed assays using peptide immunoaffinity enrichment coupled to selected reaction monitoring mass spectrometry (immuno-SRM) to detect specific peptides associated with SCID, WAS, XLA, cystinosis, and Wilson disease from dried blood spots, employing high-affinity antibodies to enrich for these peptides.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional newborn screening methods are used, then existing disorders can be detected, but primary immunodeficiencies, cystinosis, and Wilson disease cannot be reliably detected due to lack of sensitive assays for low-abundance markers
Solution Approach 1:
The patent extracts and enriches specific low-abundance peptides from complex dried blood spot samples using immunoaffinity enrichment. This extraction step isolates the target peptides (e.g., CD3ε for SCID, WASp for WAS, BTK for XLA, CTNS for cystinosis, ATP7B for Wilson disease) from the complex biological matrix, enabling their detection despite low concentrations.
Solution Approach 2:
The patent employs high-affinity antibodies as intermediaries to bridge the gap between low-abundance target peptides and the detection system. These antibodies specifically bind to target peptides with high affinity, amplifying the detectable signal and enabling reliable detection of disorders that were previously undetectable by conventional methods.
2Measurement precision
If multiplexed assays with immunoaffinity enrichment are implemented, then detection sensitivity for low-abundance markers improves, but assay complexity and cost increase
Solution Approach 1:
The patent merges multiple detection functions into a single multiplexed assay platform. By combining immunoaffinity enrichment with selected reaction monitoring mass spectrometry, the system can simultaneously detect multiple low-abundance peptides from a single dried blood spot sample, enabling screening for multiple disorders (SCID, WAS, XLA, cystinosis, Wilson disease) in one test.
Solution Approach 2:
The patent creates a universal screening platform that can detect multiple different disorders using a common technical approach. The same immunoaffinity enrichment and mass spectrometry methodology is applied across different target peptides, making the system adaptable and scalable for detecting various primary immunodeficiencies and metabolic disorders.
3Loss of time
If early detection before symptom emergence is achieved, then patient outcomes improve, but current screening methods lack the capability to detect these disorders early
Solution Approach 1:
The patent performs preliminary detection of disease markers immediately after birth using dried blood spots collected at routine newborn screening. By detecting low-abundance peptides associated with primary immunodeficiencies, cystinosis, and Wilson disease before clinical symptoms emerge, the system enables early intervention and treatment, preventing irreversible damage and improving patient outcomes.
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
The assays enable early and reliable diagnosis of these disorders, improving patient outcomes by detecting them before clinical symptoms appear, utilizing existing newborn screening procedures.
Implementation Method 1
peptide immunoaffinity enrichment coupled to selected reaction monitoring mass spectrometry (immuno-SRM) to detect specific peptides associated with SCID, WAS, XLA, cystinosis, and Wilson disease from dried blood spots, employing high-affinity antibodies to enrich for these peptides
Implementation Method 2
peptide immunoaffinity enrichment coupled to selected reaction monitoring mass spectrometry (immuno-SRM) to detect specific peptides
Data Source
AI summary
Newborn screening for primary immunodeficiencies, cystinosis, and Wilson disease is described. The newborn screening can detect these disorders from dried blood spots already routinely collected at the time of birth. Early detection of these disorders will greatly improve patient outcome as each of them can be fatal once symptoms emerge.