Elastography of 3D microtissue
We developed a new method of elastography designed for the study of micro/mesocale tissues. Our method is unique in that it uses differential interference contrast (DIC)/confocal microscopy, rather than commonly used ultrasound imaging or optical coherence tomography. See our recent publication.
The figure shows the analysis of tumor-fibroblast co-culture spheroid. (a) Von Mises strain map calculated from DIC images. (b) Overlay confocal fluorescence of tumor cells (red) and fibroblast cells (green). We found solid fibroblast cells formed a core stiffer than surrounding cancer cells, which would not have been found only with conventional fluorescence images. Scale bars = 100 µm.
A movie clip (link) is available from the article website.
Analysis of microtissues through mechanical manipulation
The key tool we developed is the chop-stick-like micromanipulator. It not only allows for the manipulation of micro/mesoscale tissues, but is capable of characterizing mechanical properties the sample. We can measure the stiffness by studying bending of the cantilevers through image analysis. To our knowledge, our study is the first to quantify the elastic moduli of cancer spheroids! Read our publication for details.
We can measure the stiffness of microtissues sized ~100 micrometer to 1 mm.
Image Analysis of Tissue Deformation
Here we explain the principle of image analysis-based strain (deformation) mapping. The photographs below show composite (core-shell) tissue phantoms made of two types of kitchen sponges (scale bar = 5 mm). One has the softer sponge in the core, and the other has the stiffer one in the core. Can you tell which is which? It is difficult just from still images.
However, when you apply a deformation, you can see the difference. Softer materials deform more than stiffer materials, which can be observed as the amount of deformation distributed within the samples.
We used this technique to study the mechanical heterogeneity in silk fibroin protein-based, bioengineered biomaterials. Please read our publication for details.
Not only for research, now we use these tissue phantoms and the indentation system for K-12 education. See also Outreach Activities page for details.