- Jafar Al-Hakkak
- Maan M. Alkaisi
- Mike Arnold
- Ali M. Azam
- Keith H.R. Baronian
- Olaf Bork
- Paula A. Brooksby
- Craig R. Bunt
- Tim David
- Alison J. Downard
- James Dunlop
- Pablo G. Etchegoin
- John J. Evans
- Alan Fernyhough
- Paul T. Gaynor
- Juliet A. Gerrard
- Patrick Gladding
- David P. L. Green
- Shaun C. Hendy
- Justin M. Hodgkiss
- Shazlina Johari
- Nigel G. Larsen
- Conrad D. Lendrum
- Duncan J. McGillivray
- Kathryn M. McGrath
- Susie J. Meade
- Peter Metcalf
- John S. Mitchell
- Lynn M. Murray
- Volker Nock
- Mike A. Packer
- Jasna Rakonjac
- Bern H. A. Rehm
- Eric C. Le Ru
- Mathieu M. Sellier
- Fahmi Samsuri
- John C. Sharpe
- Rahul K. Shastry
- Vikki L. Smithem
- Christian Soeller
- Mark P. Staiger
- Richard D. Tilley
- Jadranka Travas-Sejdic
- Nick Tucker
- Mark R. Waterland
- Geoff R. Willmott
- Donald Wlodkowic
- Tim B.F. Woodfield
- Bryon E. Wright
- Samuel S. C. Yu
- Bioimprint – Photo nanoimprint lithography of biological samples
- Characterisation of Endometrial Cancer Cells by Atomic Force Microscopy
- Force Pattern Characterization of C. elegans in Motion
- Self-propelling coalescing droplets
- Spatially Resolved Measurement of Dissolved Oxygen in Multistream Microﬂuidic Devices
- Electrical and Computer Engineering, UoC
- Department of Chemistry, UoC
- Centre for Bioengineering, UoC
- Centre for Bioengineering & Nanomedicine, UoO
- The Raman Laboratory, UoV
- Laboratory for Cell & Protein Regulation, UoO
- School of Chemical and Physical Sciences, UoV
- School of Chemical Sciences, UoA
- The Cawthron Biosecurity & Biotechnology Group
Bioimprint – Photo nanoimprint lithography of biological samples
BNN Members involved:
Detection of subtle dﬀ erences in cell surfaces and morphology that may be indicative of diseases and abnormalities such as cancer  has potential for the early diagnosis and treatment of disease and for use in biological studies. Accurate discrimination of such changes by optical microscopy remains a major challenge . High-resolution microscopic techniques such as atomic force microscopy (AFM) are much better suited to such analyses as they enable three-dimensional (3D) nanometer resolution. However, they have the major disadvantage of requiring high scanning tip forces that can damage the sensitive soft biological tissue. Blunter tips have been used to minimize the damage but they result in greatly diminished resolution . Furthermore, scanning using a tip in an aqueous environment can cause structural movement and loss of resolution due to damping eﬀects .
However, it has been predicted that AFM imaging of cells in liquid should be capable of resolutions of 50–500 nm regardless of whether the cells are living or ﬁxed [5,6]. Time-consuming preparation procedures when using either air or vacuum environments associated with TEM have been a further limitation which is exacerbated by the need for dehydration and ﬁxation, which can deform the cells and introduce artifacts in the imaging process . Such nanoscale imaging tools have therefore not been widely used in life science applications. Whilst polymers have been used in the imprinting of yeasts for quartz crystal microbalance sensors [8,9], they have only recently been applied to nanoscale imaging.
To overcome these imaging challenges, a polymer-based approach has been recently developed whereby the cells are coated with a monomer mixture, which is then polymerized over the cell surfaces [10–12] in a positive soft lithography technique . By careful selection of the monomers it is possible to obtain an imprint of the cellular surface features in the polymer once the cellular material has been washed away from the replica. This imprint replica can then be imaged using high-resolution techniques such as AFM without the concerns of cellular damage. This approach has come to be known as a “Bioimprint” technique [11,14]. When combined with AFM imaging, continuous sampling to capture snapshots of biological events and monitoring of cell conditions can be achieved to allow studies of cellular structure and cell response to physiological and noxious stimuli. Furthermore, such techniques have potential as biomedical procedures to form 3D biocompatible and bioactive scaﬀolds for tissue culture.
Previous work on obtaining Bioimprints has utilized the nonbiohazardous poly(dimethylsilxoane) (PDMS) polymer composite [10,11] and applied this to endometrial cancer cells . This has allowed high-resolution imaging of membrane morphological structures consistent with exocytosis. This technique utilized thermal setting of the polymer  and so had the disadvantage of exposing cells to very high temperatures for some minutes, followed by another curing step taking hours to complete. A UV-cured Bioimprint technique was then adopted by photocuring a siloxane copolymer to visualize pituitary cells . However, there were some signiﬁcant challenges to overcome with this approach, namely, distorted or permeation artifacts resulting from prolonged curing time, cell dehydration eﬀects, an irradiation time of several minutes which had the potential to induce alterations in cell characteristics, and the large number of curing steps that were required to complete the process. Use of methacrylic acid/ethylene glycol dimethacrylate copolymer has the advantages that the polymer will set under UV irradiation within seconds  if applied at appropriate volumes and polymerizes smoothly around surface features, making it potentially useful for application in Bioimprinting of nanoscale features. Furthermore, it can be spin-coated onto immobilized cells to produce polymer layers of various thicknesses.
While previous work has investigated the Bioimprint for high-resolution imaging and cell analysis applications, recent investigations center on using the Bioimprint as an independent cell culture substrate.
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 F. L. Dickert and O. Hayden, “Bioimprinting of polymers and sol-gel phases. Selective detection of yeasts with imprinted polymers,” Analytical Chemistry, vol. 74, no. 6, pp. 1302–1306, 2002.
 K. Seidler, P. A. Lieberzeit, and F. L. Dickert, “Application of yeast imprinting in biotechnology and process control,” Analyst, vol. 134, no. 2, pp. 361–366, 2009.
 M. M. Alkaisi, J. J. Muys, and J. J. Evans, “Bioimprint replication of single cells on a biochip,” in BioMEMS and Nanotechnology III, vol. 6799 of Proceedings of SPIE, Canberra, Australia, December 2007.
 J. J. Muys, M. M. Alkaisi, and J. J. Evans, “Nanoscale analysis by replication of cellular topography using soft lithography,” Journal of Biomedical Nanotechnology, vol. 2, no. 1, pp. 11–15, 2006.
 J. J. Muys, M. M. Alkaisi, and J. J. Evans, “Cellular replication and atomic force microscope imaging using a UV-bioimprint technique,” Nanomedicine, vol. 2, no. 3, pp. 169–176, 2006.
 G. M. Whitesides, E. Ostuni, S. Takayama, X. Jiang, and D. E. Ingber, “Soft lithography in biology and biochemistry,” Annual Review of Biomedical Engineering, vol. 3, pp. 335–373, 2001.
 J. J. Muys, M. M. Alkaisi, D. O. Melville, et al., “Cellular transfer and AFM imaging of cancer cells using Bioimprint,” Journal of Nanobiotechnology, vol. 4, article 1, 2006.
 R. H. Schmidt, K. Mosbach, and K. Haupt, “A simple method for spin-coating molecularly imprinted polymer ﬁlms of controlled thickness and porosity,” Advanced Materials, vol. 16, no. 8, pp. 719–722, 2004.
|L.M. Murray, V. Nock, M.M. Alkaisi, J.J.M. Lee, and T.B.F. Woodfield||Fabrication of polymeric substrates with micro- and nanoscale topography bioimprinted at progressive cell morphologies||Journal of Vacuum Science and Technology B: Microelectronics and Nanometer Structures: Processing, Measurement, and Phenomena||30||06F902||2012||paper|
|V. Nock, L. Murray, F. Samsuri, M. M. Alkaisi, and J. J. Evans||Microfluidic arrays for bioimprint of cancer cells||Microelectronic Engineering||88 (8)||814-816||2011||paper|
|F. Samsuri, M. M. Alkaisi, J. J. Evans, K. Chitcholtan, and J. S. Mitchell||Detection of changes in cell membrane structures using the Bioimprint technique||Microelectronic Engineering||88 (8)||1871-1874||2011||paper|
|V. Nock, L. Murray, F. Samsuri, M. M. Alkaisi and J. J. Evans||Microfluidics-assisted photo nanoimprint lithography for the formation of cellular bioimprints||Journal of Vacuum Science and Technology B||28 (6)||C6K17-C16K22||2010||paper|
|M. M. Alkaisi, J. J. Muys, and J. J. Evans||Single cell imaging with AFM using Biochip/Bioimprint Technology||International Journal of Nanotechnology||6 (3-4)||355-368||2009||paper|
|F. Samsuri, J. S. Mitchell, M. M. Alkaisi, and J. J. Evans||Formation of Nanoscale Bioimprints of Muscle Cells Using UV-Cured Spin-Coated Polymers||Journal of Nanotechnology||593410||2009||paper|
|J. J. Muys, M. M. Alkaisi, and J. J. Evans||Cellular replication and atomic force microscope imaging using a UV-Bioimprint technique||Nanomedicine: Nanotechnology, Biology and Medicine||2 (3)||169-176||2006||paper|
|J. J. Muys, M. M. Alkaisi, D. O. S. Melville, J. Nagase, P. Sykes, G. M. Parquez, and J. J. Evans||Cellular transfer and AFM imaging of cancer cells using Bioimprint||Journal of Nanobiotechnology||4 (1)||2006||paper|
|J. J. Muys, M. M. Alkaisi, and J. J. Evans||Bioimprint: Nanoscale Analysis by Replication of Cellular Topography Using Soft Lithography||Journal of Biomedical Nanotechnology||2 (1)||11-15||2006||paper|