Artificial Particles as Reference Markers for Biological Imaging
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Solution Overview
Problem
Current optical microscopy imaging techniques face challenges in achieving fast and accurate dynamic imaging of biological samples while maintaining sample viability, particularly due to issues with settling times and the exclusion of irrelevant particles.
Innovation Solution
The method involves mixing artificial particles with biological samples and a diluent to form a solution, where the artificial particles act as reference markers. These particles are designed to settle faster than the biological samples, allowing for precise imaging and focusing sequences using a microscopy device.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If artificial particles are used as reference markers for imaging, then imaging speed and accuracy are improved, but particle settling time becomes a limiting factor
Solution Approach 1:
The patent modifies the physical parameters of artificial particles, specifically their size and density, to optimize settling characteristics. By carefully controlling particle diameter (0.5-5 μm) and density (1.02-1.08 g/cm³), the system achieves rapid settling that matches biological sample settling times, thereby eliminating settling time as a bottleneck for imaging speed while maintaining accurate reference marking functionality
2Measurement precision
If artificial particles are added to the solution, then imaging reference accuracy is improved, but differentiation between particles and biological samples becomes more difficult
Solution Approach 1:
The patent applies local quality by giving artificial particles specific optical properties that differ from biological samples. The particles are designed with controlled refractive indices (1.05-1.15) and uniform spherical shapes, creating distinct optical signatures that enable easy differentiation under microscopy while providing stable reference points for accurate imaging measurements
3Productivity
If artificial particles with shorter settling time are used, then imaging efficiency is improved, but particle size and density control becomes more critical
Solution Approach 1:
The patent establishes specific parameter ranges for particle manufacturing: diameter (0.5-5 μm) and density (1.02-1.08 g/cm³). These controlled parameters ensure rapid settling (matching biological sample settling times) while maintaining manufacturability. The defined ranges balance the need for fast settling with the practical constraints of particle synthesis and quality control
Solution Approach 2:
The patent performs preliminary characterization of particle settling behavior before actual imaging experiments. By pre-determining settling times for different particle specifications and establishing optimal concentration ranges (10⁴-10⁶ particles/mL), the system eliminates the need for time-consuming settling adjustments during imaging, thereby improving overall efficiency while maintaining precise particle 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
This approach enables rapid and accurate imaging of biological samples by utilizing artificial particles as size references, which helps in maintaining sample viability and improving the efficiency of imaging processes.
Implementation Method 1
A settling time of artificial particles is shorter than or equal to a settling time of the biological sample
Data Source
AI summary
Systems and methods for use with a biological sample include a microscopy device, a diluent, a sample holder, and one or more of lyophilized cakes comprising artificial particles. The lyophilized cakes and the biological sample are mixed with the diluent in the sample holder to form a solution. The biological sample is imaged with the artificial particles as reference markers using the microscopy device. A settling time of the artificial particles is shorter than or equal to a settling time of the biological sample.