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1. Optical coherence tomography detects necrotic regions and volumetrically quantifies multicellular tumor spheroids

   Huang, Yongyang ; Wang, Shunqiang ; Guo, Qiongyu ; Kessel, Sarah ; Rubinoff, Ian ; Chan, Leo Li-Ying ; Li, Peter ; Liu, Yaling ; Qiu, Jean ; Zhou, Chao ( October 2017 , Cancer research)

   Three-dimensional (3D) tumor spheroid models have gained increased recognition as important tools in cancer research and anti-cancer drug development. However, currently available imaging approaches employed in high-throughput screening drug discovery platforms e.g. bright field, phase contrast, and fluorescence microscopies, are unable to resolve 3D structures deep inside (>50 μm) tumor spheroids. In this study, we established a label-free, non-invasive optical coherence tomography (OCT) imaging platform to characterize 3D morphological and physiological information of multicellular tumor spheroids (MCTS) growing from ~250 μm up to ~600 μm in height over 21 days. In particular, tumor spheroids of two cell lines glioblastoma (U-87more »MG) and colorectal carcinoma (HCT 116) exhibited distinctive evolutions in their geometric shapes at late growth stages. Volumes of MCTS were accurately quantified using a voxel-based approach without presumptions of their geometries. In contrast, conventional diameter-based volume calculations assuming perfect spherical shape resulted in large quantification errors. Furthermore, we successfully detected necrotic regions within these tumor spheroids based on increased intrinsic optical attenuation, suggesting a promising alternative of label-free viability tests in tumor spheroids. Therefore, OCT can serve as a promising imaging modality to characterize morphological and physiological features of MCTS, showing great potential for high-throughput drug screening.« less
2. The shape of (7) Iris as evidence of an ancient large impact?

   https://doi.org/10.1051/0004-6361/201834541  

   Hanuš, J. ; Marsset, M. ; Vernazza, P. ; Viikinkoski, M. ; Drouard, A. ; Brož, M. ; Carry, B. ; Fetick, R. ; Marchis, F. ; Jorda, L. ; et al ( April 2019 , Astronomy & Astrophysics)

   Context. Asteroid (7) Iris is an ideal target for disk-resolved imaging owing to its brightness ( V ~ 7–8) and large angular size of 0.33′′ during its apparitions. Iris is believed to belong to the category of large unfragmented asteroids that avoided internal differentiation, implying that its current shape and topography may record the first few 100 Myr of the solar system’s collisional evolution. Aims. We recovered information about the shape and surface topography of Iris from disk-resolved VLT/SPHERE/ZIMPOL images acquired in the frame of our ESO large program. Methods. We used the All-Data Asteroid Modeling ( ADAM ) shapemore »reconstruction algorithm to model the 3D shape of Iris, using optical disk-integrated data and disk-resolved images from SPHERE and earlier AO systems as inputs. We analyzed the SPHERE images and our model to infer the asteroid’s global shape and the morphology of its main craters. Results. We present the 3D shape, volume-equivalent diameter D eq = 214 ± 5 km, and bulk density ρ = 2.7 ± 0.3 g cm −3 of Iris. Its shape appears to be consistent with that of an oblate spheroid with a large equatorial excavation. We identified eight putative surface features 20–40 km in diameter detected at several epochs, which we interpret as impact craters, and several additional crater candidates. Craters on Iris have depth-to-diameter ratios that are similar to those of analogous 10 km craters on Vesta. Conclusions. The bulk density of Iris is consistent with that of its meteoritic analog based on spectroscopic observations, namely LL ordinary chondrites. Considering the absence of a collisional family related to Iris and the number of large craters on its surface, we suggest that its equatorial depression may be the remnant of an ancient (at least 3 Gyr) impact. Iris’s shape further opens the possibility that large planetesimals formed as almost perfect oblate spheroids. Finally, we attribute the difference in crater morphology between Iris and Vesta to their different surface gravities, and the absence of a substantial impact-induced regolith on Iris.« less
3. Aspiration-assisted freeform bioprinting of mesenchymal stem cell spheroids within alginate microgels

   https://doi.org/10.1088/1758-5090/ac4dd8  

   Kim, Myoung Hwan ; Banerjee, Dishary ; Celik, Nazmiye ; Ozbolat, Ibrahim T ( February 2022 , Biofabrication)

   Abstract Aspiration-assisted freeform bioprinting (AAfB) has emerged as a promising technique for precise placement of tissue spheroids in three-dimensional (3D) space enabling tissue fabrication. To achieve success in embedded bioprinting using AAfB, an ideal support bath should possess shear-thinning behavior and yield-stress to facilitate tight fusion and assembly of bioprinted spheroids forming tissues. Several studies have demonstrated support baths for embedded bioprinting in the past few years, yet a majority of these materials poses challenges due to their low biocompatibility, opaqueness, complex and prolonged preparation procedures, and limited spheroid fusion efficacy. In this study, to circumvent the aforementioned limitations, wemore »present the feasibility of AAfB of human mesenchymal stem cell (hMSC) spheroids in alginate microgels as a support bath. Alginate microgels were first prepared with different particle sizes modulated by blending time and concentration, followed by determination of the optimal bioprinting conditions by the assessment of rheological properties, bioprintability, and spheroid fusion efficiency. The bioprinted and consequently self-assembled tissue structures made of hMSC spheroids were osteogenically induced for bone tissue formation. Alongside, we investigated the effects of peripheral blood monocyte-derived osteoclast incorporation into the hMSC spheroids in heterotypic bone tissue formation. We demonstrated that alginate microgels enabled unprecedented positional accuracy (∼5%), transparency for visualization, and improved fusion efficiency (∼97%) of bioprinted hMSC spheroids for bone fabrication. This study demonstrates the potential of using alginate microgels as a support bath for many different applications including but not limited to freeform bioprinting of spheroids, cell-laden hydrogels, and fugitive inks to form viable tissue constructs.« less
4. Protective mechanism of dried blood spheroids: stabilization of labile analytes in whole blood, plasma, and serum

   https://doi.org/10.1039/D1AN01132D  

   Frey, Benjamin S. ; Damon, Deidre E. ; Allen, Danyelle M. ; Baker, Jill ; Asamoah, Samuel ; Badu-Tawiah, Abraham K. ( November 2021 , The Analyst)

   Three-dimensional (3D) dried blood spheroids form when whole blood is deposited onto hydrophobic paper and allowed to dry in ambient air. The adsorbed 3D dried blood spheroid present at the surface of the hydrophobic paper is observed to offer enhanced stability for labile analytes that would otherwise degrade if stored in the traditional two-dimensional (2D) dried blood spot method. The protective mechanism for the dried blood spheroid microsampling platform was studied using scanning electron microscopy (SEM), which revealed the presence of a passivation thin film at the surface of the spheroid that serves to stabilize the interior of the spheroidmore »against environmental stressors. Through time-course experiments based on sequential SEM analyses, we discovered that the surface protective thin film forms through the self-assembly of red blood cells following the evaporation of water from the blood sample. The bridging mechanism of red blood cell aggregation is evident in our experiments, which leads to the distinct rouleau conformation of stacked red blood cells in less than 60 min after creating the blood spheroid. The stack of self-assembled red blood cells at the exterior of the spheroid subsequently lyse to afford the surface protective layer detected to be approximately 30 μm in thickness after three weeks of storage in ambient air. We applied this mechanistic insight to plasma and serum to enhance stability when stored under ambient conditions. In addition to physical characterization of these thin biofilms, we also used paper spray (PS) mass spectrometry (MS) to examine chemical changes that occur in the stored biofluid. For example, we present stability data for cocaine spiked in whole blood, plasma, and serum when stored under ambient conditions on hydrophilic and hydrophobic paper substrates.« less
5. Aspiration-assisted bioprinting for precise positioning of biologics

   https://doi.org/10.1126/sciadv.aaw5111  

   Ayan, Bugra ; Heo, Dong Nyoung ; Zhang, Zhifeng ; Dey, Madhuri ; Povilianskas, Adomas ; Drapaca, Corina ; Ozbolat, Ibrahim T. ( March 2020 , Science Advances)

   Three-dimensional (3D) bioprinting is an appealing approach for building tissues; however, bioprinting of mini-tissue blocks (i.e., spheroids) with precise control on their positioning in 3D space has been a major obstacle. Here, we unveil “aspiration-assisted bioprinting (AAB),” which enables picking and bioprinting biologics in 3D through harnessing the power of aspiration forces, and when coupled with microvalve bioprinting, it facilitated different biofabrication schemes including scaffold-based or scaffold-free bioprinting at an unprecedented placement precision, ~11% with respect to the spheroid size. We studied the underlying physical mechanism of AAB to understand interactions between aspirated viscoelastic spheroids and physical governing forces duringmore »aspiration and bioprinting. We bioprinted a wide range of biologics with dimensions in an order-of-magnitude range including tissue spheroids (80 to 600 μm), tissue strands (~800 μm), or single cells (electrocytes, ~400 μm), and as applications, we illustrated the patterning of angiogenic sprouting spheroids and self-assembly of osteogenic spheroids.« less