Selective Procalcitonin 1-116 Detection via N-Terminal Antibody Segmentation
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Solution Overview
Problem
Current methods for determining procalcitonin (PCT) immunoreactivity in biological samples are limited in their ability to rapidly detect changes in secretion, making it difficult to assess the success of treatment or detect recurrence of infections, as they measure stable analytes with long clearance rates, leading to cumulative and interpretable concentration values.
Innovation Solution
Development of novel antibodies that selectively recognize and determine procalcitonin fractions with the first two amino acids (Ala-Pro) of PCT 1-116, allowing for the selective measurement of PCT 1-116 in biological samples without interference from PCT 3-116, using a sandwich immunoassay format.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If conventional PCT determination methods are used, then total PCT immunoreactivity is measured, but the detection of acute changes in secretion is delayed due to long clearance rates of stable analytes
Solution Approach 1:
The patent segments the total PCT analyte into two distinct components: stable PCT fragments (3-116) and unstable native PCT (1-116). By developing antibodies that specifically recognize only the native PCT 1-116 form, the method isolates the acute secretion marker from the stable background, enabling rapid detection of secretion changes without the masking effect of long-clearance fragments.
Solution Approach 2:
The invention applies local quality by creating antibodies with highly specific binding characteristics targeting only the N-terminal region (amino acids 1-116) of procalcitonin. This localized recognition ensures that only the unstable, clinically relevant native PCT form is detected, while stable processed fragments are excluded, providing acute diagnostic information.
2Loss of time
If total PCT measurement is performed, then cumulative concentration values are obtained, but rapid recognition of treatment success or infection progression is hindered
Solution Approach 1:
The measurement is segmented into two parallel assays: one for total PCT and one specifically for native PCT 1-116. The native PCT assay provides precise, time-sensitive information about treatment response, while the total PCT assay provides cumulative background data. This segmentation allows clinicians to rapidly assess treatment success through the native PCT marker without being confounded by stable fragment accumulation.
Solution Approach 2:
The method performs preliminary differentiation of PCT forms through specific antibody binding before measurement. By pre-selecting for native PCT 1-116 using N-terminal-specific antibodies, the assay prepares the sample in a way that directly reflects acute secretion status, enabling immediate and precise treatment monitoring without waiting for cumulative changes in total PCT.
3Stability of the object's composition
If antibodies recognizing PCT fragments are used, then stable analytes with long clearance rates are measured, but the ability to detect recurrence of infection is reduced
Solution Approach 1:
Instead of measuring stable PCT fragments as traditionally done, the invention inverts the approach by specifically measuring the unstable native PCT 1-116 form. This inversion allows detection of infection recurrence through rapid changes in native PCT levels, providing high productivity in detecting acute events while using stability-specific antibodies to ensure precise target recognition.
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 selective determination of PCT 1-116 provides more direct and rapid reflection of acute patient status, enabling quicker recognition of treatment success and infection progression, with concentrations of PCT 1-116 being about 1/5 to 1/8 of total PCT, offering improved diagnostic clarity.
Implementation Method 1
Development of novel antibodies that selectively recognize and determine procalcitonin fractions with the first two amino acids (Ala-Pro) of PCT 1-116
Implementation Method 2
using a sandwich immunoassay format
Data Source
AI summary
The present invention provides an immunodiagnostic method for determining procalcitonin and procalcitonin derivatives in a biological sample of a patient, in particular in the monitoring and control of treatment and the monitoring of the progression of a local or systemic bacterial infection, inflammation, sepsis or neurodegenerative disease. In particular, the method detects molecular forms of intact procalcitonin 1-116, or procalcitonin partial peptides derived therefrom that retain amino acids alanine and proline (Ala-Pro, AP) in positions 1 and 2 of the amino terminus of the complete procalcitonin 1-116. The method uses antibodies that selectively bind an epitope comprising amino acids 1 and 2 of procalcitonin 1-116 (SEQ ID NO: 1) and can distinguish between intact procalcitonin 1-116 and for example, procalcitonin 3-116.