Quantification of neurofilament light chain in physiological samples
Inventors
HRUSOVSKY, Edward Kevin • Wilson, David • Shan, Dandan • Chang, Lei • Song, Linan • Jeromin, Andreas • TOBOS, Carmen Ioana • PATEL, Purvish Prahlad
Assignees
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Publication Number
US-12287343-B2
Publication Date
2025-04-29
Expiration Date
Abstract
The present disclosure relates to immunoassays for NF-L performed on liquid samples derived from physiological fluids such as venous blood to detect the presence or absence of a physiological condition by quantifying one or a combination of NF-L determinations at concentrations indicative of the condition.
Core Innovation
The invention provides a method of testing for a neurological condition in a human subject by forming a liquid sample from a blood or plasma sample and diluting it in a diluent. The diluent comprises one or more immunoglobulins, a detergent, urea, and one or more blocking agents. The method obtains a concentration of neurofilament light chain (NF-L) in the liquid sample via a singleplex immunoassay or a single molecule array.
The method determines an NF-L concentration from the human subject and compares it with an NF-L concentration from a healthy control sample. Based on the comparison, the method assigns a risk of the neurological condition, and an increase in the NF-L concentration from the human subject compared to the healthy control is indicative of the neurological condition.
The invention includes a subject/control comparison framework that derives a classification value from the NF-L concentration using a classification model and assigns by comparing the classification value to threshold value(s), including using at least one ratio between the NF-L concentration from the human subject and the healthy control. The framework is directed to detecting and/or classifying neurological conditions where NF-L is informative, including traumatic brain injury and multiple sclerosis.
Claims Coverage
The claim set includes one independent method claim and dependent claims that refine the method with classification mechanics, specific immunoglobulin identities and concentration constraints, and diagnostic-performance constraints for traumatic brain injury.
Diluent for NF-L singleplex measurement
forming a liquid sample by diluting a blood or plasma sample taken from the subject in a diluent, wherein the diluent comprises one or more immunoglobulins, a detergent, urea, and one or more blocking agents
Singleplex NF-L concentration determination
obtaining a concentration of neurofilament light chain (NF-L) in the liquid sample via a singleplex immunoassay or a single molecule array
Subject versus healthy control comparison
comparing the NF-L concentration from the human subject with a NF-L concentration from a healthy control sample
Risk assignment from increased NF-L
assigning a risk of the neurological condition based on the comparison, wherein an increase in the NF-L concentration from the human subject compared to the NF-L concentration from the healthy control is indicative of the neurological condition
Classification value and threshold-based assignment
calculating at least one classification value based on a classification model using the obtained concentration of NF-L as an input, and assigning by comparing the at least one classification value to at least one threshold value
NF-L subject/control ratio for classification
calculating at least one classification value by determining a ratio of the NF-L concentration from the human subject compared to the NF-L concentration from the healthy control
Specific immunoglobulin identities in the diluent
wherein the one or more immunoglobulins include human IgG, bovine gamma globulin (BgG), or a combination of both
Human IgG concentration range in diluent
wherein human IgG is at a concentration between 1 mg/mL and 10 mg/mL
Traumatic brain injury performance constraints
identifying traumatic brain injury with a true positive rate of at least 75% while maintaining a false positive rate below 25%
Overall claim coverage centers on measuring NF-L from a blood or plasma-derived liquid sample using a singleplex immunoassay or single molecule array, using a diluent containing immunoglobulins, detergent, urea, and blocking agents, and assigning risk by comparing subject NF-L to healthy control NF-L. Dependent claims further specify subject/control ratio and classification model outputs with threshold values, define immunoglobulin types including human IgG and bovine gamma globulin, and impose quantitative diagnostic-performance constraints for identifying traumatic brain injury.
Stated Advantages
Assigning a risk of a neurological condition based on an increase in NF-L concentration compared to a healthy control.
Using a diluent that comprises immunoglobulins, detergent, urea, and blocking agents in obtaining an NF-L concentration via a singleplex immunoassay or a single molecule array.
Deriving classification assignment using at least one classification value from a classification model compared to at least one threshold value.
Supporting classification using a ratio of the NF-L concentration from the human subject compared to the NF-L concentration from the healthy control.
Providing quantitative performance constraints for traumatic brain injury identification (true positive rate at least 75% with false positive rate below 25%).
Documented Applications
Testing for a neurological condition in a human subject based on NF-L measurement and comparison to a healthy control sample.
Identifying traumatic brain injury using classification-model-based assignment and quantitative true/false rate constraints.
Multiple sclerosis is included among the neurological conditions refined in dependent claim scope.
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