Extracellular-controlled breast cancer cell formation and growth using non-UV patterned hydrogels via optically-induced electrokinetics

Abstract

The culturing of cancer cells on micropatterned substrates can provide insight into the factors of the extracellular environment that enable the control of cell growth. We report here a novel non-UV-based technique to quickly micropattern a poly-(ethylene) glycol diacrylate (PEGDA)-based hydrogel on top of modified glass substrates, which were then used to control the growth patterns of breast cancer cells. Previously, the fabrication of micropatterned substrates required relatively complicated steps, which made it impractical for researchers to rapidly and systematically investigate the effects of different cell growth patterns. The technique presented herein operates on the principle of optically-induced electrokinetics (OEKs) and uses computer-generated projection light patterns to dynamically pattern the hydrogel on a hydrogenated amorphous silicon (a-Si:H) thin-film, atop an indium tin oxide (ITO) glass substrate. This technique allows us to pattern lines, circles, pentagons, and more complex shapes in the hydrogel with line widths below 3 μm and thicknesses of up to 6 μm within 8 s by simply controlling the projected illumination pattern and applying an appropriate AC voltage between the two ITO glass substrates. After separating the glass substrates to expose the patterned hydrogel, we experimentally demonstrate that MCF-7 breast cancer cells will adhere to the bare a-Si:H surface, but not to the hydrogel patterned in various geometric shapes and sizes. Theoretical analysis and finite-element model simulations reveal that the dominant OEK forces in our technique are the dielectrophoresis (DEP) force and the electro-osmosis force, which enhance the photo-initiated cross-linking reaction in the hydrogel. Our preliminary cultures of breast cancer cells demonstrate that this reported technique could be applied to effectively confine the growth of cancer cells on a-Si:H surfaces and affect individual cell geometry during their growth.

3-D Non-UV Digital Printing of Hydrogel Microstructures by Optically Controlled Digital Electropolymerization

“…Requiring only visible light projection images, this technique provides potentially a low-cost and high throughput process to "print" micro polymer structures. We have demonstrated that this fabrication technique has a lateral-resolution of 3 μm (a limitation of the pixels of the optical projection system), which is sufficient for single cell studies [41]. In terms of vertical-resolution, the thickness of fabricated hydrogel structures range from tens of nanometers to hundreds of micrometers; and hence, this technology could potentially be applied for substrate surface modification and three-dimensional tissue scaffold research.…”

Measurement of single leukemia cell's density and mass using optically induced electric field in a microfluidics chip

“…OEK, essentially a dielectrophoresis (DEP) system, uses digitally and optically projected images to define virtual electrodes instead of metal electrodes. Transport, 11 separation, 12,13 rotation, 14,15 and patterning 16 of micro/nanoparticles, including cells and DNAs, are major features of OEK technology. We have recently developed an OEK-based method capable of measuring the mass and density of a single bead and yeast cell.…”

Microarray-integrated optoelectrofluidic immunoassay system

“…In conclusion, our proposed assay system provided high compatibility with conventional glass-based microarray formats thanks to the optical method for active mass transport, resulting in improved reaction efficiency with minimal sample consumption (5 ll). Based on these technological attractions, the proposed optoelectrofluidic immunoassay system is considered as one of the potential candidates to develop optically controlled micro total analysis systems (lTAS) for biological fields such as protein expression study and diagnostics by integrating various versatile manipulation methods for cells, 30 biomolecules, 31 and micro-and nano-sized particles 32 of optoelectrofluidic technologies.…”