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Longitudinal Morphological and Physiological Monitoring of Three-dimensional Tumor Spheroids Using Optical Coherence Tomography

Tumor spheroids have been developed as a three-dimensional (3D) cell culture model in cancer research and anti-cancer drug discovery. However, currently, ...

Lehigh University

Nanodrug-carrier delivery in the blood stream is strongly influenced by nanoparticle (NP) dispersion. This paper presents a numerical study on NP transport and dispersion in red blood cell (RBC) suspensions under shear and channel flow conditions, utilizing an immersed boundary fluid-structure interaction model with a lattice Boltzmann fluid solver, an elastic cell membrane model and a particle motion model driven by both hydrodynamic loading and Brownian dynamics. The model can capture the multiphase features of the blood flow. Simulations were performed to obtain an empirical formula to predict NP dispersion rate for a range of shear rates and cell concentrations. NP dispersion rate predictions from the formula were then compared to observations from previous experimental and numerical studies. The proposed formula is shown to accurately predict the NP dispersion rate. The simulation results also confirm previous findings that the NP dispersion rate is strongly influenced by local disturbances in the flow due to RBC motion and deformation. The proposed formula provides an efficient method for estimating the NP dispersion rate in modeling NP transport in large-scale vascular networks without explicit RBC and NP models.

Characterization of Nanoparticle Dispersion in Red Blood Cell Suspension by the Lattice Boltzmann-Immersed Boundary Method.

A wavy-herringbone (wavy-HB) structured microfluidic device was used to effectively and selectively capture and release circulating tumor cells (CTCs) by using immunoaffinity and magnetic force. This device was designed to create passive turbulence and increase the possibility of tumor cells colliding with the device wall. Under an external magnetic field, magnetic particles (MPs) coated with anti-EpCAM against a tumor cell surface protein (EpCAM) were immobilized over the wavy-HB surface to capture tumor cells. After removing the magnetic field, the captured cells with surplus MPs were released from the device and collected; thus, these cells could be re-cultured for further analysis. Under optimized conditions, the capture efficiency of the tumor cells can be as high as 92% ± 2.8%. Capture experiments were also performed on whole blood samples, and the capture efficiency was in a high range of 81-95%, at different tumor cell concentrations. Such a method can potentially be used for CTC sorting from patient blood samples, CTC concentration monitoring, therapeutic guidance and drug dosage choice, and further study of tumors, such as drug screening and tumor mutations.

Magnetic particles assisted capture and release of rare circulating tumor cells using wavy-herringbone structured microfluidic devices.

A facile method for generation of tumor spheroids in large quantity with controllable size and high uniformity is presented. HCT-116 cells are used as a model cell line. Individual tumor cells are sparsely seeded onto petri-dishes. After a few days of growth, separated cellular islets are formed and then detached by dispase while maintaining their sheet shape. These detached cell sheets are transferred to dispase-doped media under orbital shaking conditions. Assisted by the shear flow under shaking and inhibition of cell-to-extracellular matrix junctions by dispase, the cell sheets curl up and eventually tumor spheroids are formed. The average size of the spheroids can be controlled by tuning the cell sheet culturing period and spheroid shaking period. The uniformity can be controlled by a set of sieves which were home-made using stainless steel meshes. Since this method is based on simple petri-dish cell culturing and shaking, it is rather facile for forming tumor spheroids with no theoretical quantity limit. This method has been used to form HeLa, A431 and U87 MG tumor spheroids and application of the formed tumor spheroids in drug screening is also demonstrated. The viability, 3D structure, and necrosis of the spheroids are characterized.

Yaling Liu

Department of Mechanical Engineering,
Department of Bioengineering

Lehigh University

Longitudinal Morphological and Physiological Monitoring of Three-dimensional Tumor Spheroids Using Optical Coherence Tomography

Yaling Liu

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Mechanical Engineering,Department of Bioengineering

Lehigh University

Longitudinal Morphological and Physiological Monitoring of Three-dimensional Tumor Spheroids Using Optical Coherence Tomography

Department of Mechanical Engineering,
Department of Bioengineering