Flow Cytometry Ribbon Core Stream Volumetric Throughput
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Solution Overview
Problem
Current flow cytometry technologies face limitations in analyzing rare events, such as Circulating Tumor Cells (CTCs) and fetal cells, due to low volumetric sample delivery and analytical throughput, leading to inefficiencies and potential false negatives, which can impact patient outcomes.
Innovation Solution
A particle analyzer utilizing a non-Gaussian, substantially nondiffracting light beam to create a ribbon-like core stream in a flowcell, allowing for increased volumetric throughput and improved detection capabilities by maintaining a uniform light intensity across a larger core stream, enabling faster and more reliable analysis and sorting of cells based on multiple selection criteria.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional flow cytometry is used for rare-event analysis, then detection capability is maintained, but volumetric throughput is insufficient leading to long analysis times and potential false negatives
Solution Approach 1:
The patent transitions from conventional point-by-point flow cytometry to a planar imaging approach, where a wide-field illumination source illuminates an entire plane of the core stream simultaneously. This dimensional change from 1D (single file) to 2D (parallel planes) enables thousands of cells to be analyzed in parallel while maintaining detection reliability through spatially-resolved detection across the illuminated area.
Solution Approach 2:
The patent divides the core stream into multiple parallel planes that can be simultaneously illuminated and detected. By segmenting the analysis into spatial zones across the width of the core stream, the system processes multiple cell layers in parallel, dramatically increasing volumetric throughput while maintaining the ability to detect rare events in each segment.
2Adaptability or versatility
If surface-antigen binding technology is used, then magnetic separation is achieved, but cell populations not defined by surface antigens are missed
Solution Approach 1:
The patent creates a universal flow cytometry platform that can detect cells through multiple mechanisms beyond surface-antigen binding. The wide-field illumination and spatially-resolved detection enable identification of cells based on intrinsic optical properties, morphology, and multiple markers simultaneously, making the system adaptable to various cell types including those without surface antigens, thereby reducing false negatives.
3Ease of operation
If conventional flow cytometry protocols are used, then cell analysis is performed, but complex sample preparation steps are required
Solution Approach 1:
The patent performs preliminary enrichment of rare cells in the core stream before the actual analysis step. By using the wide-field illumination to pre-identify and spatially separate target cells during the flow process, the system reduces the need for complex post-preparation steps and enables faster turnaround from sample to result.
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 significantly enhances the analysis rate of flow cytometry, allowing for rapid and accurate detection of rare cells, potentially improving cancer patient outcomes by enabling earlier and more sensitive metastatic process detection, and simplifying sample preparation procedures.
Implementation Method 1
A particle analyzer utilizing a non-Gaussian, substantially nondiffracting light beam to create a ribbon-like core stream in a flowcell, allowing for increased volumetric throughput and improved detection capabilities by maintaining a uniform light intensity across a larger core stream
Implementation Method 2
a detector configured to detect a signal from said core stream, the signal resulting from an interaction of a particle in said core stream with said light beam
Data Source
AI summary
A particle analyzer, comprising a source of a substantially nondiffracting light beam; a flow path configured to produce in a flowcell a ribbon-like core stream having a specific cross-sectional aspect ratio; the flowcell being configured to expose a segment of the core stream to the light beam; a detector configured to receive a signal resulting from an interaction of a particle in the core stream with the light beam; a first sorting actuator connected with the flowcell, downstream of the exposed segment of core stream; a plurality of sorting channels in fluid connection with the flow path and downstream of the first actuator; the actuator having multiple actuation states, each state configured to direct at least one part of the core stream to a corresponding channel; a second sorting actuator connected with the flowcell, opposite the first actuator, and operable in coordination with the first actuator.