Ex Vivo Motility Contrast Imaging for 3D Tissue Drug Response
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Solution Overview
Problem
Current methods for assessing tissue viability and drug response in three-dimensional (3D) tissues are limited by the need for invasive and potentially toxic assays, and lack the ability to effectively measure multicellular resistance, which is critical for understanding cancer drug sensitivities and tumor microenvironment effects.
Innovation Solution
Biodynamic imaging (BDI) using optical coherence imaging (OCI) and motility contrast imaging (MCI) provides a label-free, non-invasive method to extract subcellular motions and functional responses in 3D tissues, allowing for the generation of drug response spectrograms and identification of regions with maximum ascent/descent to predict therapeutic responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If exogenous vital dyes are used to measure cellular viability and metabolic activity, then measurement capability is improved, but tissue toxicity and invasiveness increase
Solution Approach 1:
The patent replaces chemical staining methods with optical coherence imaging, a non-invasive optical technique that measures tissue viability through light scattering properties without requiring exogenous dyes or chemicals, thereby eliminating tissue toxicity while maintaining measurement capability
Solution Approach 2:
The patent introduces optical coherence imaging as an intermediary measurement method that indirectly assesses cellular viability through optical properties of intact tissue, avoiding direct chemical interaction with cells that would cause toxicity
2Ease of manufacture
If two-dimensional monolayer cultures are used for drug response assays, then assay simplicity is improved, but biological relevance and genomic profile preservation deteriorate
Solution Approach 1:
The patent transitions from two-dimensional monolayer cultures to three-dimensional tissue constructs, adding the vertical dimension to better replicate in vivo tissue architecture, cell-cell interactions, and pharmacokinetics while maintaining assay feasibility through optical imaging capabilities
3Measurement precision
If standard two-dimensional chemosensitivity assays are used, then measurement capability is improved, but ability to detect multicellular resistance deteriorates
Solution Approach 1:
The patent uses three-dimensional tissue constructs that preserve multicellular interactions and gradients, enabling detection of multicellular resistance phenomena that are absent in two-dimensional monolayer cultures where cells lack natural morphology and microenvironment
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 the evaluation of tissue viability and drug response in 3D tissues, capturing dynamic processes and motions, and providing unique fingerprints of drug action, thereby improving the prediction of drug efficacy and mechanisms of action.
Implementation Method 1
Biodynamic imaging (BDI) using optical coherence imaging (OCI) and motility contrast imaging (MCI) provides a label-free, non-invasive method to extract subcellular motions
Data Source
AI summary
In a method for ex vivo evaluation of tissue response, a target biological sample is placed in a chamber of a sample holder. Biodynamic imaging (BDI) is performed on the sample to extract BDI data of the entire sample, optical coherence imaging (OCI) data is generated from the BDI data; and then motility contrast imaging (MCI) data is generated from the OCI data. The MCI data is used to select an area of the ex vivo sample having the highest normalized standard deviation (NSD) value, indicative of a region of desirable responsiveness to a stimuli. The sample is subjected to a perturbation or external condition and an MCI analysis is performed on the selected area to determine the tissue response to the perturbation or external condition. In one aspect, the selected area or region of interest is obtained using a gradient descent method.