Affinity Transport Particles for Rapid Biological Sample Analysis
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Solution Overview
Problem
Current methods for analyzing biological samples, such as LC and HPLC, are inefficient due to long separation times, high costs, and the inability to handle complex samples like whole blood, which contain thousands of molecular species, making rapid and high-volume analysis challenging.
Innovation Solution
The method involves using affinity transport particles (ATPs) to selectively bind analytes of interest, followed by a size-restricted sorbent to retain unbound agents, and a disassociating/enriching column configuration to isolate and separate analytes quickly, allowing for mass spectrometric analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If LC and HPLC are used to analyze biological samples, then sensitivity and selectivity are improved, but separation time increases significantly
Solution Approach 1:
The invention divides the separation process into two distinct stages: a rapid preliminary separation stage using a first column with large pores to separate major components, followed by a targeted analysis stage using mass spectrometry. This segmentation allows the bulk of the separation work to be done quickly while maintaining the precision needed for sensitive detection of specific analytes.
Solution Approach 2:
The method performs preliminary separation of biological samples using a first column with large pores (0.01-10 μm) before mass spectrometry analysis. This preliminary action removes the bulk of interfering substances and separates major components, reducing the complexity of the sample presented to the mass spectrometer and enabling faster overall analysis while maintaining sensitivity.
2Measurement precision
If traditional chromatography is used for high-volume analysis, then separation capability is improved, but device complexity and cost increase
Solution Approach 1:
The invention changes the key parameter of column pore size from the conventional small pores (0.1-10 μm) to large pores (0.01-10 μm). This parameter change enables faster flow rates and reduced backpressure while maintaining adequate separation capability for the intended application, thereby reducing device complexity and operational cost for high-volume analysis.
3Measurement precision
If reverse-phase chromatography is used to separate biological agents, then separation by hydrophobic interaction is improved, but the number of peaks and interfering substances increases
Solution Approach 1:
The invention extracts and removes interfering substances from the biological sample using a first column with large pores before the sample reaches the mass spectrometer. By taking out these interfering components in a preliminary separation step, the method reduces the number of peaks and interfering substances that would otherwise complicate the analysis, while still maintaining the ability to separate and detect target analytes.
4Measurement precision
If affinity transport particles are used to bind analytes, then selectivity is improved, but the complexity of the binding domain increases
Solution Approach 1:
The invention applies local quality by concentrating the binding functionality in a specific region (the binding domain) of the affinity transport particle, while keeping the rest of the particle structure simple. The binding domain is specifically designed to interact with target analytes, while the core particle structure remains straightforward, thereby achieving high selectivity without excessive overall complexity.
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 enables rapid and efficient analysis of biological samples by reducing preparation time and costs, effectively isolating analytes of interest from complex samples, facilitating qualitative and quantitative analysis.
Implementation Method 1
one or more stripping columns, the stripping column including a stationary phase comprising a size-restricted access sorbent configured to retain biological agents not bound to an affinity transport particle
Implementation Method 2
affinity transport particles (ATPs) to selectively bind analytes of interest
Data Source
AI summary
The present invention relates to methods for continuous or near-continuous separation and purification of samples, particularly biological samples, to reduce the number or volume of non-targeted analytes in those samples to enable improved mass spectrometric analysis of analytes of interest, and apparatuses for conducting those methods, utilizing a transport agent with a core domain and a binding domain, the transport agent exceeding 200 kiloDaltons or 10 nm, and the binding domain targeted to the analytes of interest, in conjunction with size-exclusion based chromatography to separate the transport agent-analyte of interest complex from non-targeted analytes that are not bound, or are only non-specifically bound, to the transport agent.