Solid-Phase Affinity Selection Mass Spectrometry Transfer
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Solution Overview
Problem
Conventional affinity selection by mass spectrometry (ASMS) methods are limited by time-consuming separation of free drugs from protein-drug complexes, and existing solid-phase devices like magnetic particles require careful handling to avoid ingestion into the mass spectrometer during transfer.
Innovation Solution
An improved method and apparatus for transferring candidate molecules into an open-port sampling interface (OPI) using a solvent-based capture fluid to separate solid-phase devices, with optional magnetic or size-based trapping, and acoustic ejection to introduce samples without suction, allowing for efficient separation and ionization of compounds.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional solution phase ASMS is used, then affinity selection can be performed, but analysis speed is limited due to time-consuming separation of free drugs from protein-drug complex
Solution Approach 1:
The patent extracts the separation function from the liquid phase and transfers it to the solid phase. Solid phase devices (magnetic particles, SPME fibers) are used to capture and retain drug molecules through affinity interactions, while the liquid phase is used only for introducing the drug mixture and for eluting bound drugs. This extraction of the separation function to the solid phase eliminates the time-consuming liquid phase separation step and enables direct infusion of separated compounds to the mass spectrometer.
Solution Approach 2:
The patent introduces solid phase devices as intermediary elements between the liquid phase drug mixture and the mass spectrometer. These intermediaries (magnetic particles, SPME fibers) perform the separation function by binding to drug molecules with affinity, acting as a mediator that transfers compounds from the liquid phase to a form suitable for direct MS analysis, thereby eliminating the need for conventional liquid phase chromatographic separation.
2Measurement precision
If magnetic particles are used for solid phase ASMS, then capture sensitivity is improved due to larger surface area, but magnetic particles may be ingested into the mass spectrometer during transfer
Solution Approach 1:
The patent extracts the magnetic particles from the liquid phase transfer process and retains them in the solid phase. Magnetic particles are used to capture drugs in the liquid phase, then the bound complexes are transferred to the solid phase where separation occurs. The magnetic particles remain stationary in the solid phase, eliminating their presence in the liquid phase transfer to the mass spectrometer and preventing ingestion into the MS instrument.
Solution Approach 2:
The patent segments the system into distinct liquid phase and solid phase compartments. The liquid phase handles sample introduction and binding, while the solid phase handles separation and MS interface. This segmentation isolates the magnetic particles to the solid phase compartment, preventing them from entering the mass spectrometer while maintaining their capture functionality.
3Ease of operation
If suction-based aspiration is used to transfer samples, then sample transfer can be achieved, but the process is complex and requires careful handling
Solution Approach 1:
The patent replaces the mechanical suction-based aspiration system with a direct infusion system. Instead of using suction to draw samples through a needle and syringe, the system uses direct infusion of the liquid phase containing bound drugs directly into the mass spectrometer. This substitution eliminates the complex mechanical aspiration system while simplifying the transfer process and reducing the risk of particle ingestion.
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 simplifies the handling of magnetic beads and other solid-phase devices, reduces the need for suction-based aspiration, and enhances the speed and efficiency of compound separation and analysis by filtering out solid-phase devices before mass spectrometry, thereby improving the overall analysis speed and reducing contamination risks.
Implementation Method 1
binding one or more compounds from the plurality of compounds to the probe; removing the probe and bound one or more compounds from the solution
Implementation Method 2
introduced (without the solid phase devices) into the OPI using a process that does not require the sample to be aspirated off using suction
Implementation Method 3
an a external magnetic field to trap the solid phase devices before delivering the sample to the MS ion source
Implementation Method 4
acoustic ejection to introduce samples without suction, allowing for efficient separation and ionization of compounds
Implementation Method 5
ionizing the one or more compounds
Data Source
AI summary
In a system for affinity selection by mass spectrometry, wherein a plurality of drug candidates in solution are separated based on affinity, a method is provided comprising introducing a solid-phase device having binding affinity for a selected protein into the solution, binding at least one of the plurality of drug candidates to the solid-phase device as a selected drug candidate, washing the solid-phase device and selected drug candidate to separate unbound material, sampling the selected drug candidate in capture fluid flowing through a sampling region of an open port sampling interface and directing the sampled selected drug candidate and capture fluid to an ionization source.