First-ever microfluidic BioMEMS device to study the mechanisms of cell migration and deformation

Cancer cells have the ability to invade blood vessels and find their way into the bloodstream. Once there, these infected cells can easily travel to other parts of the body and attack healthy organs.

While migration and deformability have been identified as key factors that determine the invasive capability of cancer cells, it has been almost impossible to study these cell characteristics quantitatively until now.

IBN Scientists Dr M M Maran, Dr Francis Tay, Dr Peilin Mao and student Leonard Chu, have invented the first-ever microfluidic BioMEMS device to study the mechanisms of cell migration and deformation.

Said Dr Maran, the project’s Lead Scientist: “Several studies have suggested that cancer cells gain access to the blood vessels and lymphatic vessels through open inter-endothelial gaps or by inducing the opening of closed gaps.

“It is also believed that tumor vessels are ‘leaky’ with a low blood flow rate. Within a vascularized tumor, cancer cells may easily enter newly formed vessels, which often lack intact endothelial cells.

“However, while these observations provide a good qualitative description of tumor invasion, they do not provide us with quantitative information about the size of the inter-endothelial gaps that allow cancer cells to pass through or how cancer cells are able to migrate through these gaps. That is why we have developed a device that can be used to study the mechanism of cell migration and deformation in blood vessels.”

IBN’s device has a multi-gap design that mimics the microenvironment in the body to enable the study of the migration, deformation and proliferation of cells through gaps in vessels. It aims to help researchers to quantify the extent that cells can deform themselves through gaps in vessels. This information will contribute to a better understanding of the characteristics of cell invasion and metastatic mechanism.

The novel device, which is easy to fabricate, consists of two or three micro channels that are parallel to each other with micro pores or gaps between 1 them. The micro gaps, which range in width from 3 µm to 30 µm, are designed to simulate inter-endothelial gaps, capillaries and other blood vessel leakages. Using an optical microscope, the cell condition inside the fabricated device and the deformation and migration of attached cells can easily be observed.

Studies conducted by IBN using MC3T3 osteoblast cells that are approximately 30 µm in diameter show that cell migration is not impeded by the micro gaps, and that these cells are even able to squeeze through a 3 µm gap. The cells simply attach to the surface and gradually migrate across the gaps, while deforming themselves. In order to move across a gap, the cells first project very thin cytoplasm, which then pulls the nucleus gradually across the gap. This deformation does not have a significant effect on the cells, provided that there are enough nutrients and gases and the cell is not ruptured.

“Our device allows you to observe the effect of drugs on tumor cells. Therefore, it can be used to evaluate different types of cancer drugs, such as drugs targeting the endothelial cell gaps, or those that target the migration or deformation of cancer cells. This device can also be used as an educational tool for cell studies,” shared Dr Maran. A US patent has been filed for the device early this year and IBN is seeking partners to commercialize it.

http://www.ibn.a-star.edu.sg

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