14
C. Hu and G. Popescu
[110], and malaria infection [111]. Combining with artificial intelligence, QPI-based
tissue imager opens new directions for achieving automated diagnosis [112–114].
1.4.2 Cellular Dynamics
The cell growth and proliferation is a complicated process, which involves various
activities such as producing proteins, communication with neighboring cells, interacting with the extracellular matrix, and migration [115]. Accurately recording and
monitoring these phenomena, in general, is challenging. Since QPI reports the nonaqueous content within the sample referred to as dry mass, this label-free imaging
modality offers an alternative means to measure cellular-level mass production in a
noninvasive manner [61, 116, 117]. The local dry mass, ρ, is calculated as
ρ =
λϕ
2πγ
(1.19)
where λ is the central wavelength of illumination light, ϕ the measured phase shift,
and γ = 0.2 ml/g the refractive increment of protein. Thus, the total mass of a
region of interest is then calculated by integrating over the area. This simple math
operation allows quantitative investigation of dynamics at cellular level, e.g., cell
growth and division, emergence of neuronal network [61, 118–121]. In addition, by
fitting the QPI data to a diffusion equation, biophysical features, e.g., advection and
diffusion, can also be extracted to interpret the mass transport capabilities of the
studied sample [43, 73, 122–126]. Recently, we have seen that several other models
are invented to probe a sample’s biophysical properties, further expanding the scope
of QPI applications.
1.4.3 Tomography
Tomographic imaging is an invaluable method for understanding the internal structure and dynamics in biological cells and tissue. In the past, 3D live cell imaging was
mostly done by fluorescent-based techniques, such as confocal microscopy, which
have limitations due to photobleaching and phototoxicity [127]. QPI tomography
produces refractive index distribution in 3D and directly offers chemical composition and structural information of a sample, which is complementary to conventional
methods [40, 128, 129]. For example, spiculated red blood cell structure was visualized by a white-light diffraction tomography [130]. A time-lapse tomogram of a
chimeric antigen receptor T cell killing a leukemic B cell was obtained using optical
diffraction tomography [1]. More recently, QPI tomography has been extended to
measure thick specimen such as embryos, brain slices and organoids. Figure 1.10
shows 3D structural changes in a bovine embryo over several days [24].
C. Hu and G. Popescu
[110], and malaria infection [111]. Combining with artificial intelligence, QPI-based
tissue imager opens new directions for achieving automated diagnosis [112–114].
1.4.2 Cellular Dynamics
The cell growth and proliferation is a complicated process, which involves various
activities such as producing proteins, communication with neighboring cells, interacting with the extracellular matrix, and migration [115]. Accurately recording and
monitoring these phenomena, in general, is challenging. Since QPI reports the nonaqueous content within the sample referred to as dry mass, this label-free imaging
modality offers an alternative means to measure cellular-level mass production in a
noninvasive manner [61, 116, 117]. The local dry mass, ρ, is calculated as
ρ =
λϕ
2πγ
(1.19)
where λ is the central wavelength of illumination light, ϕ the measured phase shift,
and γ = 0.2 ml/g the refractive increment of protein. Thus, the total mass of a
region of interest is then calculated by integrating over the area. This simple math
operation allows quantitative investigation of dynamics at cellular level, e.g., cell
growth and division, emergence of neuronal network [61, 118–121]. In addition, by
fitting the QPI data to a diffusion equation, biophysical features, e.g., advection and
diffusion, can also be extracted to interpret the mass transport capabilities of the
studied sample [43, 73, 122–126]. Recently, we have seen that several other models
are invented to probe a sample’s biophysical properties, further expanding the scope
of QPI applications.
1.4.3 Tomography
Tomographic imaging is an invaluable method for understanding the internal structure and dynamics in biological cells and tissue. In the past, 3D live cell imaging was
mostly done by fluorescent-based techniques, such as confocal microscopy, which
have limitations due to photobleaching and phototoxicity [127]. QPI tomography
produces refractive index distribution in 3D and directly offers chemical composition and structural information of a sample, which is complementary to conventional
methods [40, 128, 129]. For example, spiculated red blood cell structure was visualized by a white-light diffraction tomography [130]. A time-lapse tomogram of a
chimeric antigen receptor T cell killing a leukemic B cell was obtained using optical
diffraction tomography [1]. More recently, QPI tomography has been extended to
measure thick specimen such as embryos, brain slices and organoids. Figure 1.10
shows 3D structural changes in a bovine embryo over several days [24].