Making structures for cell engineering.

This is a mainly historical account of the events, methods and artifacts arising from my collaboration with Adam Curtis over the past twenty years to make exercise grounds for biological cells. Initially the structures were made in fused silica by photo-lithography and dry etching. The need to make micron-sized features in biodegradable polymers, led to the development of embossing techniques. Some cells response to grooves only a few tens of nanometers deep--this led to a desire to find the response of cells to features of nanometric size overall. Regular arrays of such features were made using electron beam lithography for definition of the pattern. Improvements were made in the lithographic techniques to allow arrays to be defined over areas bigger than 1 cm2. Structures with microelectrodes arranged inside guiding grooves to allow the formation of sparse predetermined networks of neurons were made. It is concluded that the creation of pattern, as in vivo, in assemblies of regrown cells in scaffolds may well be necessary in advanced cell engineering applications.

[1]  C. Wilkinson,et al.  Topographical control of cell behaviour: II. Multiple grooved substrata. , 1990, Development.

[2]  Stephen Britland,et al.  Morphogenetic guidance cues can interact synergistically and hierarchically in steering nerve cell growth , 1996 .

[3]  C. Wilkinson,et al.  Arrays of nano-dots for cellular engineering , 2003 .

[4]  Matthew J Dalby,et al.  Nucleus alignment and cell signaling in fibroblasts: response to a micro-grooved topography. , 2003, Experimental cell research.

[5]  C. Wilkinson,et al.  Embossing of nanoscale features and environments , 1997 .

[6]  P. Connolly,et al.  Simultaneous multisite recordings and stimulation of single isolated leech neurons using planar extracellular electrode arrays , 1994, Journal of Neuroscience Methods.

[7]  Artificially Induced Nerve Cell Patterning or Real Neural Networks , 1992 .

[8]  A. Curtis,et al.  Effective extra-cellular recording from vertebrate neurons in culture using a new type of micro-electrode array , 2002, Journal of Neuroscience Methods.

[9]  Patricia Connolly,et al.  Finite-element analysis applied to extracellular microelectrode design , 1991 .

[10]  M. Peckerar,et al.  Synthetic Microstructures in Biological Research , 1992, Springer US.

[11]  C. Wilkinson,et al.  An extracellular microelectrode array for monitoring electrogenic cells in culture. , 1990, Biosensors & bioelectronics.

[12]  A Curtis,et al.  Guidance and activation of murine macrophages by nanometric scale topography. , 1996, Experimental cell research.

[13]  S. Chou,et al.  Imprint Lithography with 25-Nanometer Resolution , 1996, Science.

[14]  C. Wilkinson,et al.  Topographical control of cell behaviour. I. Simple step cues. , 1987, Development.

[15]  P Connolly,et al.  Cell guidance by ultrafine topography in vitro. , 1991, Journal of cell science.