Search bioRxiv⌕ Search

Biology subjects

Papautsky, I.

Publications and source records attributed to Papautsky, I..

3 recordsLinked to original sources

Cell-specific heteroclinic orbits govern interaction dynamics in inertial microfluidics for circulating tumour cell separation

Cancer survival rates increase with earlier diagnosis. However, many cancers are diagnosed only after symptoms develop, in the later stages of cancer progression. We need a diagnostic tool that can detect cancer earlier. Circulating tumour cells (CTCs) are cells that detach from the main tumour and can enter the bloodstream. The capture and analysis of CTCs can provide an early indicator of cancer. However, rarity of CTCs in blood makes their efficient capture challenging. Inertial microfluidics can be utilised for a label-free separation of CTCs from white blood cells (WBCs) by manipulating cells in the microchannel based on cell properties, achieving good separation performance. Inertial microfluidic devices mainly rely on size-based separation. However, residual WBC carryover limits complete separation. Here, we show that cell mechanical heterogeneity plays a large role in the separation process and should be considered in the design of these devices. We simulate the migration dynamics of CTCs and WBCs in a straight microchannel using a 3D lattice-Boltzmann-immersed-boundary-finite-element solver. Our results demonstrate that WBC migration behaviour changes depending on the deformability of a CTC. The size and deformability of the cells have been shown to determine the cell-specific heteroclinic orbits leading to different interaction types, these interactions alter WBC migration resulting in more/less WBC carryover. This work highlights that both cell-specific heteroclinic orbits and single cell migration rates should be considered in the design of inertial microfluidics for separation.

bioengineering↗

Microfluidic Platform for Drug Response Profiling in NSCLC Patient-Derived Organoids

Tumor models that recapitulate 3D architecture are essential for understanding how cellular organization and microenvironmental interactions govern therapeutic response in human cancers. Here, we developed a microfluidic microphysiological system that enables controlled and scalable culture and drug testing of non-small cell lung cancer spheroids and patient-derived organoids. The platform integrated U-shaped microwells with dual-channel loading to support de novo spheroid formation, efficient trapping of pre-formed spheroids, and loading of intact organoids with reduced size heterogeneity. Tumor spheroids and organoids maintained high viability and structural integrity during long-term on-chip culture, and constrained microscale confinement produced ellipsoidal geometries that deviate from idealized spherical assumptions. Baseline genotype-dependent responses to KRAS G12C and EGFR inhibitors were preserved across agarose and microfluidic formats, establishing a validated reference state. Building on this baseline, fibroblast- and endothelial-derived cues consistently attenuated responses to targeted therapies across conditioned media, mixed co-culture, and spatially organized configurations. Resistance phenotypes converged on a dominant role for paracrine signaling, while increasing architectural complexity primarily enhanced morphological fidelity rather than altering therapeutic response. These findings establish a microphysiological framework that decouples tumor-intrinsic drug sensitivity from microenvironment-mediated modulation, enabling the systematic evaluation of paracrine resistance mechanisms in NSCLC.

bioengineering↗

Numerical study of the size-based, shear-induced separation ofcirculating tumour cells from white blood cells in liquid biopsies

Circulating tumour cells (CTCs) are promising biomarkers for early cancer detection, yet their extreme rarity in blood necessitates efficient separation from white blood cells (WBCs) in lysed liquid biopsies. Inertial microfluidics offers a high-throughput, label-free approach to this challenge by leveraging size-dependent lateral migration. However, experimental observations reveal that WBCs migrate more rapidly than predicted, reducing separation performance. Using 3D lattice-Boltzmann-immersed-boundary-finite-element simulations, we characterized the migration dynamics of CTCs and WBCs in a straight microchannel. Our results reveal that the presence of a CTC enhances WBC cross-streamline migration, providing a mechanistic explanation for WBC contamination in CTC-enriched outlets. The numerical model capturing heterochiral orbital dynamics was validated experimentally, confirming the role of intercellular hydrodynamic interactions. These findings underscore the critical role of intercellular interactions in inertial microfluidic systems and provide guidance for optimizing suspension concentration and channel geometry to improve purity in rare cell isolation.

bioengineering↗