Biodynamic digital holography was used to obtain phenotypic profiles of canine non-Hodgkin B-cell lymphoma biopsies treated with standard-of-care chemotherapy. Biodynamic signatures from the living 3D tissues were extracted using fluctuation spectroscopy from intracellular Doppler light scattering in response to the molecular mechanisms of action of therapeutic drugs that modify a range of internal cellular motions. The standard-of-care to treat B-cell lymphoma in both humans and dogs is a combination CHOP therapy that consists of doxorubicin, prednisolone, cyclophosphamide and vincristine. The proportion of dogs experiencing durable cancer remission following CHOP chemotherapy was 68%, with 13 out of 19 dogs responding favorably to therapy and 6 dogs failing to have progression-free survival times greater than 100 days. Biodynamic signatures were found that correlate with inferior survival times, and biomarker selection was optimized to identify specific Doppler signatures related to chemoresistance. A machine learning classifier was constructed based on feature vector correlations and linear separability in highdimensional feature space. Hold-out validation predicted patient response to therapy with 84% accuracy. These results point to the potential for biodynamic profiling to contribute to personalized medicine by aiding the selection of chemotherapy for cancer patients.
Intracellular dynamics in living tissue are dominated by active transport driven by bioenergetic processes far from thermal equilibrium. Intracellular constituents typically execute persistent walks. In the limit of long mean free paths, the persistent walks are ballistic, exhibiting a “Doppler edge” in light scattering fluctuation spectra. At shorter transport lengths, the fluctuations are described by lifetime-broadened Doppler spectra. Dynamic light scattering from transport in the ballistic, diffusive, or the crossover regimes is derived analytically, including the derivation of autocorrelation functions through a driven damped harmonic oscillator analog for light scattering from persistent walks. The theory is validated through Monte Carlo simulations. Experimental evidence for the Doppler edge in three-dimensional (3D) living tissue is obtained using biodynamic imaging based on low-coherence interferometry and digital holography.
The creation of pseudo-magnetic fields in strained graphene has emerged as a promising route to investigate intriguing physical phenomena that would be unattainable with laboratory superconducting magnets. The giant pseudo-magnetic fields observed in highly deformed graphene can substantially alter the optical properties of graphene beyond a level that can be feasible with an external magnetic field, but the experimental signatures of the influence of such pseudo-magnetic fields have yet to be unveiled. Here, using time-resolved infrared pump-probe spectroscopy, we provide unambiguous evidence for slow carrier dynamics enabled by the pseudo-magnetic fields in periodically strained graphene. Strong pseudo-magnetic fields of ~100 T created by non-uniform strain in graphene on nanopillars are found to significantly decelerate the relaxation processes of hot carriers by more than an order of magnitude. Our findings offer alternative opportunities to harness the properties of graphene enabled by pseudo-magnetic fields for optoelectronics and condensed matter physics.
The ability to precisely control moiré patterns in two-dimensional materials has enabled the realization of unprecedented physical phenomena including Mott insulators, unconventional superconductivity, and quantum emission. Along with the twist angle, the application of independent strain in each layer of stacked two-dimensional materials—termed heterostrain—has become a powerful means to manipulate the moiré potential landscapes. Recent experimental studies have demonstrated the possibility of continuously tuning the twist angle and the resulting physical properties. However, the dynamic control of heterostrain that allows the on-demand manipulation of moiré superlattices has yet to be experimentally realized. Here, by harnessing the weak interlayer van der Waals bonding in twisted bilayer graphene devices, we demonstrate the realization of dynamically tunable heterostrain of up to 1.3%. Polarization-resolved Raman spectroscopy confirmed the existence of substantial heterostrain by presenting triple G peaks arising from the independently strained graphene layers. Theoretical calculations revealed that the distorted moiré patterns via heterostrain can significantly alter the electronic structure of twisted bilayer graphene, allowing the emergence of multiple absorption peaks ranging from near-infrared to visible spectral ranges. Our experimental demonstration presents a new degree of freedom towards the dynamic modulation of moiré superlattices, holding the promise to unveil unprecedented physics and applications of stacked two-dimensional materials.
Three-dimensional (3D) tissue cultures are replacing conventional two-dimensional (2D) cultures for applications in cancer drug development. However, direct comparisons of in vitro 3D models relative to in vivo models derived from the same cell lines have not been reported because of the lack of sensitive optical probes that can extract high-content information from deep inside living tissue. Here we report the use of biodynamic imaging (BDI) to measure response to platinum in 3D living tissue. BDI combines low-coherence digital holography with intracellular Doppler spectroscopy to study tumor drug response. Human ovarian cancer cell lines were grown either in vitro as 3D multicellular monoculture spheroids or as xenografts in nude mice. Fragments of xenografts grown in vivo in nude mice from a platinum-sensitive human ovarian cell line showed rapid and dramatic signatures of induced cell death when exposed to platinum ex vivo, while the corresponding 3D multicellular spheroids grown in vitro showed negligible response. The differences in drug response between in vivo and in vitro growth have important implications for predicting chemotherapeutic response using tumor biopsies from patients or patient-derived xenografts.
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