Quantitative Phase Imaging for Tumor Therapy Screening
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Solution Overview
Problem
Current cell-based assays for determining drug responses in cancer treatment are limited by their inability to capture dynamic single-cell responses and require longer turnaround times, making them costly and less effective in rapidly informing patient care.
Innovation Solution
The development of a quantitative phase imaging (QPI) system that enables real-time, label-free measurement of individual cell growth by quantifying changes in mass over time, allowing for rapid determination of drug sensitivity, cytotoxicity, and response heterogeneity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional endpoint assays (e.g., CellTiter-Glo) are used to measure cell viability, then reproducible drug response data with high signal-to-noise ratio can be obtained, but the ability to capture dynamic single-cell responses is lost
Solution Approach 1:
The patent replaces traditional biochemical endpoint assays with quantitative phase imaging (QPI) microscopy that uses optical interference patterns to measure cell mass and growth dynamics. This substitution enables non-invasive, label-free real-time monitoring of individual cell responses while maintaining measurement precision through phase shift detection.
Solution Approach 2:
The invention implements continuous real-time imaging of cell cultures throughout the drug exposure period, capturing temporal dynamics of cell growth and death. This continuous monitoring provides uninterrupted data streams that reveal cytostatic versus cytotoxic responses, replacing discrete endpoint measurements with ongoing observation.
2Loss of time
If real-time imaging assays (e.g., Incucyte) are used to measure cell proliferation, then temporal dynamics of drug response can be elucidated, but the system complexity and cost increase
Solution Approach 1:
The patent employs simple, inexpensive optical components including LED illumination sources and standard phase contrast microscopy equipment rather than complex automated imaging systems. This approach reduces device complexity and cost while maintaining real-time imaging capability through straightforward phase imaging analysis.
Solution Approach 2:
The QPI system requires minimal intervention once set up, with automated image acquisition and processing that eliminates the need for complex operational procedures. The system self-calibrates using reference measurements and automatically generates drug response parameters from phase imaging data.
3Measurement precision
If suspended microchannel resonators are used to measure cell mass accumulation, then highly sensitive changes in cell growth can be detected, but the system is limited to non-adherent cell types and requires flow through individual resonators
Solution Approach 1:
The patent develops a QPI microscopy system that can universally image both adherent and non-adherent cell types in standard culture formats. The phase imaging technique is not limited by cell attachment properties, enabling broad applicability across diverse cancer cell lines and tissue types while maintaining high measurement precision.
Solution Approach 2:
The invention divides the measurement field into multiple imaging zones within a single well plate, allowing parallel monitoring of numerous individual cells or small clusters. This segmentation approach provides statistical robustness equivalent to resonator arrays while maintaining simplicity of a single optical platform.
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
QPI provides a multiparametric approach that can characterize cytostatic/cytotoxic responses and track the emergence of resistant subpopulations, offering a richer understanding of cell dynamics and response variability compared to traditional endpoint assays.
Implementation Method 1
QPI measures the growth rate of individual cells by quantifying changes in mass versus time
Data Source
AI summary
A microscope imaging system including a microscope having a stage with a well plate having a plurality of therapy treatment samples, an array of light emitting diodes (LEDs) to illuminate the plurality of therapy treatment samples, and a camera to capture images of the plurality of therapy treatment samples over a period of time using the array of LEDs. The microscope imaging system including an electronic controller configured to receive a plurality of images of the plurality of therapy treatment samples over the period of time from the camera, determine a cell mass for each therapy treatment sample based on each image, track the cell mass over the period of time for each therapy treatment sample, determine a plurality of response parameters for each therapy treatment sample based on the tracked cell mass, and determine a treatment response for each therapy treatment sample based on the plurality of response parameters.