Vesselin Paunov1 Anupam Das1 Jevan Medlock1 Leigh Madden1 David Allsup2

1, University of Hull, Hull, , United Kingdom
2, Hull York Medical School, Cottingham, , United Kingdom

Biomprinting technology has been recently developed to capture proteins, viruses and entire living cells via their structural and chemical information. Bioimprinting techniques can permanently capture an impression of biological samples into polymer surfaces with promising approaches for early cancer diagnosis [1,2], developing selective antimicrobial therapies and formulations [3,4]. Here we report a novel in-vitro approach for the removal of myeloblasts from peripheral blood samples of acute myeloid leukaemia patients utilizing a cell shape recognition technology. Due to size and shape differences between myeloblasts and normal white blood cells, myeloblasts represent an ideal target for bioimprinting. In this work, we have developed the bioimprinting technology to replicate myeloblasts (AML cells) based on their cell shape and size. Myeloblasts were inactivated with fixatives to preserve the cells structural and morphological information. Monolayers of fixed myeloblast cells were prepared by immobilisation on a polyelectrolyte pre-treated glass slides and partially protected by a film of glucose solution. Curable polymer (PDMS) was used to the imprint the exposed part of the cell monolayer and was peeled off after curing. Positive replica of the PDMS bioimrint of AML cell monolayers was prepared and the surface pattern was replicated on a large scale by using roll-to-roll printing on PET foil. These bioimprints were surface modified to promote weak adhesion to the myeloblasts which allow them to be trapped selectively on the surface of the bioimprint based on cell shape recognition. We present the results of our myeloblast cell recognition experiments as a function of the cell concentration and surface coatings of the produced cell imprints. The results indicate that the cell imprinting technology can be used to capture the AML cells based on their shape and size. We demonstrate the selectivity of the cell imprints in retention of the cells of matching shape in a mixture with other cells. The removal of myeloblasts from the normal white blood cells based on interaction with a negative bioimprinted surface which selectively attracts and retains myeloblasts. This technology is expected to find application in AML cell separation devices capable of removing myeloblasts from peripheral blood of AML patients which can lead to new blood cancer therapies.

[1] J. Medlock, A.A.K. Das, L.A. Madden, D.J. Allsup, V.N. Paunov, Chem. Soc. Rev, 2017, 46, 5110.
[2] K. Ren, N. Banaei, R.N. Zare, ACS Nano, 2013, 7, 6031.
[3] J. Borovicka, W. J. Metheringham, L.A. Madden, C.D. Walton, S.D. Stoyanov, V.N. Paunov, V.N., J. Am. Chem. Soc., 2013, 135, 5282.
[4] J. Borovicka, S.D. Stoyanov, V.N. Paunov, Nanoscale, 2013, 5, 8560.