Multi-chambered Rotating Apparatus for Homogenous Cell Block Uniformity
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Solution Overview
Problem
Current methods for creating cell blocks for immunohistochemistry and in situ hybridization lack reliable, uniformly distributed cell controls, leading to inconsistent staining and analysis, which hampers the use of immunohistochemistry as a 'top-tier' biomarker assay.
Innovation Solution
A multi-chambered-tiered Homogenous Cell Mixture (HCM) apparatus ensures even distribution of cells by rotating tiers and using interchangeable top chambers with holes to separate single cells, combined with a fixation solution to create a homogenous cell block with precise ratios of cell types, suitable for use as a standard in immunohistochemistry studies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If cell pellets are fixed in formalin and embedded in paraffin using conventional methods, then cell blocks can be created, but the cells become clumped and unevenly distributed, leading to inconsistent staining and analysis
Solution Approach 1:
The apparatus divides the cell embedding process into multiple sequential chambers (first chamber, second chamber, third chamber) that process cells in stages. Each chamber performs a specific function in the embedding sequence, allowing controlled distribution of cells throughout the paraffin block rather than creating clumps in a single step.
Solution Approach 2:
The apparatus employs rotating tiers with interchangeable top chambers that can be swapped during operation. This dynamic configuration allows different chamber arrangements to be used for different cell types or experimental requirements, maintaining consistent cell distribution while adapting to various imaging and analysis needs.
2Manufacturing precision
If cell blocks are created without controlled distribution methods, then the process is simpler and faster, but cell densities vary throughout the block, preventing consistent use as standards in immunohistochemistry
Solution Approach 1:
The embedding process is divided into multiple chambers that sequentially process cells. The first chamber receives cells, the second chamber distributes them through rotating tiers, and the third chamber completes the embedding. This segmentation ensures uniform cell density while managing complexity through modular design.
Solution Approach 2:
The rotating tiers with interchangeable top chambers serve multiple functions: they distribute cells uniformly, accommodate different cell types, and adapt to various experimental requirements. This multi-functionality reduces the need for separate apparatus for different applications, managing overall system complexity.
3Reliability
If conventional embedding methods are used, then the apparatus is simpler, but cell blocks cannot provide homogeneous tissue with controlled cell ratios for reliable biomarker analysis
Solution Approach 1:
The apparatus segments the embedding process into controlled stages across multiple chambers, each contributing to the final homogeneous cell distribution. This segmentation enables precise control over cell ratios and tissue homogeneity, which are critical for reliable biomarker analysis, while the modular nature manages apparatus complexity.
Solution Approach 2:
The apparatus controls embedding parameters such as cell density, distribution pattern, and tissue homogeneity through adjustable processes in each chamber. By changing and optimizing these parameters during the embedding process, the system achieves reliable cell blocks for biomarker analysis while managing the complexity through systematic parameter control.
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
The apparatus produces cell blocks with evenly distributed cells, ensuring consistent cell ratios throughout, enhancing the reliability of immunohistochemistry assays and allowing for precise biomarker analysis.
Implementation Method 1
a multi-chambered-tiered Homogenous Cell Mixture (HCM) apparatus, for creating a cell block comprising a homogenous mixture of cells
Implementation Method 2
embedding cellular materials within a formalin fixed paraffin substrate
Implementation Method 3
embedding cellular materials within a formalin fixed paraffin substrate
Data Source
AI summary
Homogenous DNA or RNA cell blocks used as a standard and comprising uniformly distributed cells, or ratio of cells, for use as a positive control for a biomarker in immunohistochemistry slide scanning and image analysis. The cell blocks are made using a Homogenous Cell Mixture (HCM) apparatus comprising a rotating multi-tiers that de-clump and filter single cells downward to mix with a fixation liquid-3% agarose. The uniform rotation of the tiers is under the operational control of a motorized mechanism, and results in a cell mixture comprising a constant density of cells, which is then transferred into molds to make formalin fixed paraffin embedded (FFPE) cell blocks. The size of the molds is also determined based upon a computation that factors in the total number of cells (e.g. density) in a cell block that a user desires, and the total cell volume for a specific cell type selected.