Structured Biological Sample Carriers for Sequential Mass Cytometry
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Solution Overview
Problem
Mass cytometry and imaging mass spectrometry face inefficiencies in introducing biological samples, with commercial mass cytometers having only 30% cell introduction efficiency and low pixel recording rates due to washout times and aerosol plume contamination, limiting throughput and accuracy.
Innovation Solution
Structured biological material is arranged on a carrier with discrete sites for sequential introduction into an ionization source, eliminating multimers and improving processing rates by maintaining sample separation and minimizing contamination through controlled desorption and gas flow management.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If laser ablation is used to extract elemental tags from tissue pixels, then imaging mass cytometry can be performed, but the washout time of the laser ablation cell and gas conduits limits the pixel recording rate to about 30 pixels per second
Solution Approach 1:
The tissue sample is divided into discrete pixels that are sequentially introduced into the mass spectrometer. Each pixel is processed individually through structured sample preparation where tissue is sectioned and positioned in a grid pattern, allowing systematic sequential analysis that maximizes instrument throughput while maintaining spatial resolution.
Solution Approach 2:
Tissue samples are pre-sectioned, pre-stained with affinity probes, and pre-positioned on carriers in a structured manner before analysis. This preliminary preparation eliminates the need for real-time sectioning and positioning during analysis, allowing the system to operate at maximum pixel recording rates without sacrificing imaging capability.
2Quantity of substance
If aerosol plume is formed during laser ablation and transported through gas conduit, then sample can be introduced to ICP source, but aerosol plume contamination of neighboring pixels and loss during transport occurs
Solution Approach 1:
The harmful aerosol plume formation step is extracted and eliminated from the sample introduction process. Instead of using laser ablation that creates aerosols requiring long washout times, the patent employs direct desorption methods that release material without forming contaminating aerosol plumes, thereby eliminating cross-contamination between pixels and improving signal fidelity.
Solution Approach 2:
A carrier gas system with optimized flow dynamics serves as an intermediary to transport desorbed material directly to the ICP source without forming aerosol plumes. The gas flow is carefully controlled to maintain discrete material packets and prevent mixing between adjacent pixels, eliminating contamination while enabling efficient sample introduction.
3Measurement precision
If commercial mass cytometer is used for cell analysis, then mass cytometry can be performed, but cell introduction efficiency is only about 30%
Solution Approach 1:
Cells are segmented and presented individually in a structured format on carriers. The sample introduction system is designed to deliver cells one at a time in a controlled manner, ensuring that each cell is properly introduced into the mass cytometer without loss, thereby achieving near 100% introduction efficiency while maintaining analytical precision.
Solution Approach 2:
The physical and chemical parameters of the sample introduction system are optimized to match the requirements of the mass cytometer. This includes adjusting gas flow rates, pressure conditions, and temporal spacing between cell introductions to maximize efficiency. The system parameters are tuned to ensure optimal cell delivery without aggregation or loss, achieving high throughput while maintaining measurement accuracy.
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 enhances sample processing rates and simplifies data analysis by ensuring discrete, sequential introduction of biological material, reducing contamination and increasing the precision of mass spectrometry results.
Implementation Method 1
performing laser ablation of a sample using laser radiation
Implementation Method 2
desorbing a slug of sample material using laser radiation
Implementation Method 3
ionizing the desorbed sample material
Data Source
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AI summary
Apparatus and methods for delivering biological samples to an ICP source of a mass cytometer are disclosed. Biological material is disposed on a plurality of discrete sites on a carrier. The plurality of discrete sites are configured to retain biological material and to release the biological material upon application of energy. The carrier is positioned in proximity to a gas conduit and upon release from the discrete sites, the biological material becomes entrained in a gas flow, which delivers discrete portions of biological material through the conduit to the ICP source for analysis by mass cytometry. The apparatus and methods can provide a continuous stream of discrete portions of biological material to a mass cytometer.