Sentinel MRM Screening for Retention Time Variability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Conventional MRM workflows in targeted protein assays and drug compound quantification face challenges with retention time variability, instrument transferability, and reliance on costly antibody enrichment processes, leading to inconsistent LC methods and increased complexity in clinical and toxicology laboratories.
Innovation Solution
Implementing a scout or sentinel MRM transition system that triggers groups of MRM transitions and adjusts separation parameters, such as LC gradient time, to maintain consistency across instruments and reduce retention time variability, eliminating the need for antibody enrichment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If manual handling of assay plates is used, then flexibility in assay design is maintained, but labor intensity and error rates increase
Solution Approach 1:
The automation system is divided into separate functional modules: a first robotic arm for picking probes, a second robotic arm for placing probes, and a third robotic arm for plate manipulation. Each module operates independently but coordinates through a control system, allowing the system to handle complex assays while maintaining modularity and reducing overall system complexity.
Solution Approach 2:
The robotic arms are designed with universal capabilities to perform multiple functions: probe picking, probe placement, plate picking, plate placing, and seal application. This multi-functionality allows a single automated system to replace multiple manual operations, reducing labor intensity without requiring separate specialized devices for each task.
2Productivity
If automated robotic arms are used, then labor intensity decreases, but system complexity and cost increase
Solution Approach 1:
Multiple robotic arms are merged into a single integrated workstation that shares common infrastructure including the control system, coordinate mapping database, and workspace environment. This consolidation allows high-throughput automation while managing complexity through shared resources rather than independent systems for each function.
Solution Approach 2:
The system uses coordinate mapping to transform physical positions into standardized coordinates, allowing the robotic arms to operate with precise parameter control. This parameter-based approach enables high throughput by efficiently managing motion paths and timing without requiring overly complex mechanical designs.
3Measurement precision
If coordinate mapping is performed, then positioning precision improves, but data processing time increases
Solution Approach 1:
Coordinate mapping is performed in advance during an initialization phase before actual assay operations begin. The system maps the positions of all plates, wells, and features once, storing this spatial information in a database. During subsequent high-throughput operations, the pre-mapped coordinates are retrieved and used directly, eliminating the need for real-time mapping and maintaining both precision and speed.
4Productivity
If multiple robotic arms operate simultaneously, then assay throughput increases, but coordination complexity increases
Solution Approach 1:
The control system continuously monitors the positions and states of all robotic arms, making real-time adjustments to coordinate their operations. This feedback mechanism allows multiple arms to operate in parallel with precise timing, managing coordination complexity through active control rather than rigid pre-programming, thereby maintaining high throughput.
Data Source
Figure 1
Figure 2
Figure 3
AI summary
One or more known compounds are separated from a mixture using a separation device that allows processor-controlled adjustment of a separation parameter. The separated compounds are ionized and, for each cycle of a plurality of cycles, a mass spectrometer executes on the ion beam a series of MRM transitions read from a list. Two or more contiguous groups of MRM transitions to be monitored separately are received. Each group includes at least one sentinel transition that identifies a next group that is to be monitored and identifies a value for the separation parameter for the next group. A first group is placed on the list. When a sentinel transition of the first group is detected, a next group identified by the sentinel transition is placed on the list and the separation parameter is adjusted to a value identified by the sentinel transition for the next group.