Microstructure - Scientific Background

Microfabrication is a combination of processes and techniques used to construct physical objects with sizes ranging from hundreds of microns to hundreds of nanometers. This technology takes advantage of established semiconductor fabrication processes, used to make integrated circuits, and, over the past two decades, has been used for the fabrication of tools with applications in biology, medicine, and biomedical engineering.

In their native physiological environment, cells constantly encounter and respond to a multitude of signals, such as growth factor and cytokine stimulation, cell-cell signalling, interaction with the extracellular matrix (ECM), and physical parameters like stiffness, topography and shear stress. A key challenge in cell biology is the design of experimental methods and specific assays to disentangle the contribution of these cell-governing parameters. Conventional cell culture supports like tissue culture flasks and Petri dishes represent only a trivial approximation of the complex microenvironment in which cells reside. Recent technological developments in material science and microfabrication have allowed new abilities to better mimic this complexity and control over a wider range of environmental parameters.

These technologies can be employed not only for the control of the chemical and physical properties of a free surface, but also for the development of microfluidic devices allowing the control of liquid flow in channels with typical sizes ranging from 1 micron up to millimetres.

Microfluidics is particularly intriguing for stem cell analysis since at the moment it is the only technology capable of providing spatial and temporal control over cell growth and stimuli by combining surfaces that mimic complex biochemistries and geometries of the ECM with microfluidic channels that regulate the transport of fluids and soluble factors, allowing researchers to modulate pluripotent stem cell renewal and differentiation through biochemical and mechanical stimulation.

The potential of microfluidic systems lies also in the physics of the microscale. By understanding and leveraging microscale phenomena, microfluidics can be used to perform experiments not possible on the macroscale, allowing new functionality and experimental paradigms to emerge. For example, microstructuring has been used for the development of high throughput systems able to perform cell stiffness analysis and sorting without using any molecular probes; it has also been used in the development of droplet microfluidics which enables previously inaccessible high throughput screening applications, including single-cell and single-molecule assays.