Modular Particle Analyzer for Label-Free Small Particle Detection
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Solution Overview
Problem
Conventional flow cytometers have fixed architectures that are ill-suited for analyzing small particles like extracellular vesicles and bacteria, and require exogenous fluorescent labels, leading to delays and high costs, while techniques like culturing and microscopy lack speed and statistical significance.
Innovation Solution
A configurable flow cytometry apparatus with modular components, including adjustable excitation sources, detection modules, and fluidic control, enabling flexible operation for various samples, and label-free analysis using endogenous fluorescence.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional flow cytometry with fixed architecture is used, then the device structure is simple, but it is ill-suited for analyzing small particles like extracellular vesicles and bacteria
Solution Approach 1:
The flow cytometer is divided into modular components including interchangeable flow cells, selectable excitation sources, and configurable detection modules. Each module can be independently selected or replaced based on the specific analysis requirements, enabling adaptation to different particle sizes and sample types without redesigning the entire system.
Solution Approach 2:
The system incorporates adjustable flow rates, variable excitation wavelengths, and configurable detection parameters that can be dynamically changed between measurements. This dynamic configurability allows the same device to be optimized for different applications, from small extracellular vesicles to larger bacterial cells.
2Measurement precision
If exogenous fluorescent labels are used, then detection sensitivity is improved, but operational time and cost increase
Solution Approach 1:
The system exploits the endogenous fluorescence naturally present in biological particles such as bacteria and cells. By detecting intrinsic fluorescent molecules without requiring exogenous labels, the system eliminates incubation steps while maintaining detection sensitivity, thereby reducing operational time and cost.
3Productivity
If high flow rate is used, then productivity is improved, but detection sensitivity for small particles decreases
Solution Approach 1:
The flow rate is dynamically adjusted based on the size and concentration of particles being analyzed. For small particles like extracellular vesicles, lower flow rates are used to increase transit time and detection sensitivity, while higher flow rates are employed for larger particles or when sample concentration is high, thus optimizing both productivity and detection precision for each specific application.
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
Enables rapid, sensitive, and cost-effective analysis of small particles and cells, adaptable to different samples without exogenous labels, improving statistical significance and reducing operational complexity.
Implementation Method 1
Flow cytometry has the benefit of rapid interrogation of larger sample sizes, along with the capacity for high event detection rates, but generally requires the use of added ('exogenous') fluorescent biochemical labels to mark and help detect cells or other biological or microbiological particles of interest
Implementation Method 2
a first detection module... a first photodetector configured to detect the third substantially collimated light beam, and a second photodetector configured to detect the fourth substantially collimated light beam
Data Source
AI summary
This disclosure relates to configurable particle analyzer apparatuses and methods. In some embodiments, a modular particle analyzer includes a stray light blocking module including a focusing lens, a pinhole, and a collimating lens. The focusing lens is configured to focus light emitted from the flowcell through the pinhole. The pinhole is configured to block stray or scattered light emitted from the flowcell. The collimating lens is configured to substantially collimate the light exiting the pinhole to output a substantially collimated light beam. A modular particle analyzer may alternatively, or additionally, include a rod-and-cage architecture. A particle analyzer may alternatively, or additionally, include a sheath pressure control module and a sample pressure control module. Further, a particle analyzer may alternatively, or additionally, include a sample probe wash. Any of the embodiments described herein may be combined with any one or more of the other embodiments described herein.