Calibrated Cell Counting Chambers for High-Throughput Accuracy
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Solution Overview
Problem
Existing cell counting technologies require significant time for large sample analysis, lack adequate calibration, and fail to provide confidence in measurement accuracy due to variations in sample concentration and composition, especially for diverse biological samples.
Innovation Solution
Incorporation of well-defined microscale markings and features in sample chambers, analysis units, and multi-well plates for automated calibration and assurance of cell measurements, including varying chamber heights, fluorescent colors, and focus registration to ensure accurate cell counting and viability assessment without dilution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If automated cell counters are used for single sample detection, then operation time is reduced and operator-dependent variations are minimized, but a great amount of time is still required when a large number of samples need to be analyzed
Solution Approach 1:
The system divides the cell counting process into multiple independent imaging chambers with different chamber heights (e.g., 10 µm, 20 µm, 30 µm, 40 µm, 50 µm, 100 µm). Each chamber can be imaged independently and in parallel, allowing the system to process multiple samples simultaneously. This segmentation enables the automated counter to handle large numbers of samples efficiently while maintaining ease of operation.
Solution Approach 2:
The invention introduces chamber height as an additional dimension for sample analysis. By varying the chamber height across multiple imaging chambers, the system creates a vertical dimension that enables simultaneous multi-depth imaging. This dimensional approach allows parallel processing of samples at different concentrations and depths, dramatically increasing throughput while maintaining automated operation.
2Adaptability or versatility
If traditional hemocytometer manual counting is used, then flexibility in analysis is maintained, but significant time is required and operator-dependent variations occur
Solution Approach 1:
The imaging chambers are pre-configured with defined features at specific depths and positions before sample loading. These features include reference markers, depth indicators, and calibration elements that are already in place to guide automated imaging and analysis. This preliminary preparation eliminates the need for manual focusing and measurement during the counting process, reducing counting time while maintaining analysis flexibility.
Solution Approach 2:
The system creates multiple copies of imaging chambers with identical structural features but different chamber heights. Each chamber contains replicated reference features and measurement markers that can be imaged automatically. This copying approach allows the system to maintain the flexibility of manual analysis methods while eliminating the time-consuming aspects through automated imaging of replicated structures.
3Productivity
If automated image-based cell counting is performed on biological samples with varying concentration and composition, then high-throughput analysis is achieved, but confidence in measurement accuracy is reduced without proper calibration
Solution Approach 1:
The invention introduces defined features as intermediary reference elements within the imaging chambers. These features include fluorescent beads, reflective markers, and depth reference structures that serve as mediators between the imaging system and the biological samples. The defined features provide known reference points for calibration, allowing the automated system to accurately measure cell concentration, size, and depth across varying sample conditions while maintaining high throughput.
Solution Approach 2:
The system utilizes multiple chamber heights as varying parameters to accommodate samples with different concentrations and compositions. By changing the chamber height parameter, the system can optimize imaging conditions for different sample types without compromising measurement accuracy. The defined features at various depths and heights provide reference points that remain valid across parameter changes, ensuring precision during high-throughput analysis.
4Productivity
If multiple imaging chambers with varying heights are used for parallel sample analysis, then high-throughput capability is achieved, but device complexity increases
Solution Approach 1:
The invention merges multiple imaging chambers with different chamber heights into a single integrated device. The chambers are arranged in an array configuration and share common structural elements, fluidic connections, and imaging optics. This merging approach allows parallel processing of multiple samples while avoiding the complexity of operating completely separate devices. The unified design maintains high throughput while simplifying operation through a single integrated system.
Solution Approach 2:
The imaging chambers are designed with universal features that allow them to serve multiple functions. Each chamber contains defined features that can be used for calibration, depth reference, and concentration measurement across different sample types. The chambers can accommodate various sample concentrations and compositions while maintaining consistent measurement capabilities. This multi-functionality reduces device complexity by eliminating the need for specialized chambers for different analysis requirements.
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, high-throughput, and calibrated cell counting with built-in quality assurance, ensuring consistent focus, size measurement, and fluorescence calibration, thereby improving the reliability of cell count data across diverse biological samples.
Implementation Method 1
comprises one or more optically transparent windows suitable for observation or analysis of the liquid sample inside the imaging chamber
Implementation Method 2
the defined features exhibit one or more fluorescent colors in one or more intensities
Data Source
AI summary
The invention provides novel sample chambers, units and multi-well plates, and systems and methods thereof, for built-in measurement assurance of cell counting methods and calibrated and/or quality-assured measurement and analysis of diverse types of biological cells, e.g., cell count, cell size, cell concentration, cell sub-population, cell morphology, cell viability, etc.