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Effects of biomaterials for Lab-on-a-chip production on cell growth and expression of differentiated functions of leukemic cell lines

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Abstract

The rapid increase of the applications for Lab-on-a-chip devices has attracted the interest of researchers and engineers on standard process of the electronics industry for low production costs and large scale development, necessary for disposable applications. The printed circuit board technology could be used for this purpose, in particular for the wide range of materials available. In this paper, assays on biocompatibility of materials used for Lab-on-a-chip fabrication has been carried out using two tumor cell lines growing in suspension, the human chronic myelogenous leukemia K562 cell line, able to undergo erythroid differentiation when cultured with chemical inducers, and the lymphoblastoid cell line (LCL), extensively used for screening of cytotoxic T-lymphocytes (CTLs). We have demonstrated that some materials strongly inhibit cell proliferation of both the two cell lines to an extent higher that 70–75%, but only after a prolonged exposure of 3–6 days (Copper, Gold over Nickel, Aramid fiber filled epoxy uncured, b-stage epoxy die attach film, Tesa 4985 adhesive tape, Pyralux uncured, Copper + 1-octodecanethiol). However, when experiments were performed with short incubation time (1 h), only Aramid fiber filled epoxy uncured was cytotoxic. Variation of the results concerning the other materials was appreciable when the experiments performed on two cell lines were compared together. Furthermore, the effects of the materials on erythroid differentiation and CTL-mediated LCL lysis confirmed, in most of the cases, the data obtained in cytotoxic and antiproliferative tests.

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Abbreviations

PCB:

Printed circuit board

CTLs:

Cytotoxic T-lymphocytes

LCL:

Lymphoblastoid cell line

ITRS:

International technology roadmap for semiconductors

RCC:

Resin coated copper

DAF:

Die attach film

PDMS:

Poly(dimethylsiloxane)

SAMs:

Self-assembled monolayers

ODT:

Octadecanethiol

PF before lam:

Polyurethane film before lamination

PF after lam:

Polyurethane film after lamination

PP:

Polyurethane powder

Certonal FC-732T:

Certonal FC-732 tempered

EBV:

Epstein–Barr Virus

FBS:

Fetal bovine serum

EBNA-3:

EBV nuclear antigen 3

HLA-A2:

Human leukocyte antigen A2

E:T:

Effector:target

Cpm:

Counts per minute

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Acknowledgements

Thanks to Manuel Seckel and Rene Jansen for the precious laboratory work. This research is funded by the EU CoChiSe Project (project reference: 034534). Roberto Gambari is granted by FIRB 2002 (Fondo per gli Investimenti nella Ricerca di Base, Italy), by AIRC (Associazione Italiana per la Ricerca sul Cancro, Italy), by Fondazione Cassa di Risparmio di Padova e Rovigo (CARIPARO, Italy) and by Telethon (contract GGP07257).

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Authors and Affiliations

  1. BioPharmaNet, Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy

    Federica Destro, Monica Borgatti, Riccardo Gavioli & Roberto Gambari

  2. Fraunhofer Institute for Reliability and Microintegration (IZM), Berlin, Germany

    Bruno Iafelice, Tanja Braun, Jörg Bauer, Lars Böttcher & Erik Jung

  3. Advanced Research Center on Electronic Systems (ARCES), University of Bologna, Bologna, Italy

    Bruno Iafelice & Roberto Guerrieri

  4. MindSeeds Laboratories, Bologna, Italy

    Massimo Bocchi

Authors
  1. Federica Destro
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  2. Monica Borgatti
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  3. Bruno Iafelice
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  4. Riccardo Gavioli
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  8. Erik Jung
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  9. Massimo Bocchi
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  10. Roberto Guerrieri
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  11. Roberto Gambari
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Corresponding author

Correspondence to Roberto Gambari.

Additional information

Federica Destro and Monica Borgatti have contributed equally to this study.

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Supplementary materials Fig. 1S

Covering of edges of a sample material embedded by PDMS in a 96-well plate. Pictures show PDMS, marked by an arrow (pointing the well wall) and a circle, dispensed at different dispensing time (from top-left picture): 1.0, 1.2, 1.5, 1.7, 2.0, 2.3, 2.5, 2.8, and 3.1 s; applied pressure (1.5 bar) and internal diameter of the dispenser tip (0.020’) are fixed. (JPEG 699 kb)

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Destro, F., Borgatti, M., Iafelice, B. et al. Effects of biomaterials for Lab-on-a-chip production on cell growth and expression of differentiated functions of leukemic cell lines. J Mater Sci: Mater Med 21, 2653–2664 (2010). https://doi.org/10.1007/s10856-010-4125-2

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  • DOI: https://doi.org/10.1007/s10856-010-4125-2

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