Motility Contrast Imaging for Deep Tissue Cellular Motion
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current microscopic imaging techniques struggle to effectively image cellular motion in three-dimensional tissues deep within living organisms, as they suffer from degradation in resolution with increasing probe depth and lack the ability to non-destructively detect motility throughout a volume, which is crucial for assessing the effects of anti-cancer drugs.
Innovation Solution
Motility contrast imaging (MCI) uses digital off-axis holography with coherence-domain gating to provide volume sectioning, allowing for the imaging of cellular motion up to 1 mm in depth by utilizing fully-developed speckle fields and interference patterns to differentiate types of sub-cellular motion, enabling the use of multicellular tumor spheroids for in vitro drug testing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional microscopic imaging techniques are used to image cellular motion in three-dimensional tissues, then imaging capability is provided, but resolution degrades with increasing probe depth
Solution Approach 1:
The patent introduces optical coherence tomography (OCT) as an intermediary technique that uses low-coherence light to achieve depth sectioning. The OCT system acts as a mediator between the light source and the tissue, using coherence gating to isolate signals from specific depths, thereby maintaining resolution at various probe depths within the tissue volume.
Solution Approach 2:
The patent transitions from conventional two-dimensional surface imaging to three-dimensional volumetric imaging by introducing the depth dimension through OCT technology. This allows cellular motion to be tracked throughout the entire volume of the tissue, not just at the surface, effectively adding a spatial dimension to the imaging capability.
2Volume of stationary object
If conventional imaging methods are used to detect motility throughout a volume, then volume imaging is attempted, but the ability to non-destructively detect motility is lost
Solution Approach 1:
The patent replaces mechanical or invasive imaging methods with optical coherence tomography, which uses non-ionizing low-coherence light to image tissue. This substitution of the imaging mechanism allows for non-destructive, non-invasive detection of cellular motion throughout the tissue volume, maintaining tissue viability while achieving volumetric imaging.
3Measurement precision
If single-mode optical coherence tomography is used for imaging, then spatial resolution is achieved, but the ability to simultaneously image multiple diffraction-limited areas is limited
Solution Approach 1:
The patent extends the OCT system to perform multiple functions simultaneously: it can image multiple diffraction-limited areas in parallel, track cellular motion dynamics, and provide three-dimensional volumetric information. This multi-functionality allows the same optical system to achieve both high spatial resolution and high productivity by capturing multiple regions of interest simultaneously.
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
MCI effectively tracks cellular motility changes in response to anti-cancer drugs, providing high-contrast images of active and inactive areas within tumor spheroids, enabling the differentiation of drug effects on viable and necrotic regions, and allowing for the construction of volumetric motility images, thus overcoming the limitations of existing imaging methods.
Implementation Method 1
a reference beam intersects the backscattered object beam at an angle to produce a series of interference fringes that modulate Fourier-domain information
Implementation Method 2
The speckle-fields of MCI arise from the interference of multiple scatterers with random phases within a coherence volume inside the tissue
Implementation Method 3
The holographic coherence gate localizes the detected motion to within a thin slab inside the tissue with a thickness determined by the coherence length of the laser
Data Source
AI summary
A system for motility contrast imaging a biological target within tissue comprising a CCD array; an illumination source for generating an incoming beam; a first beam splitter for receiving the incoming beam and producing an object beam and a reference beam; a second beam splitter for illuminating a multitude of biological targets with the object beam and for directing backscattered object beams towards the CCD array; a computer-controlled delay stage for zero-path-matching the reference beam to the backscattered object beams; a reference beam that intersects the backscattered object beams at an angle to produce a series of interference fringes that modulate Fourier-domain information; and a computer for receiving a time series of Fourier-domain information. The interference fringes between the backscattered object beam and the reference beam are recorded by the CCD array and passed to the computer which constructs a digital hologram at successive times.