TY - JOUR
T1 - High-throughput electrochemical sensing platform for screening nanomaterial-biomembrane interactions
AU - Owen, Joshua
AU - Kuznecovs, Maksims
AU - Bhamji, Raeesa
AU - William, Nicola
AU - Domenech-Garcia, Natalia
AU - Hesler, Michelle
AU - Knoll, Thorsten
AU - Kohl, Yvonne
AU - Nelson, Andrew
AU - Kapur, Nikil
N1 - Publisher Copyright:
© 2020 Author(s).
PY - 2020/2/1
Y1 - 2020/2/1
N2 - A high-throughput, automated screening platform has been developed for the assessment of biological membrane damage caused by nanomaterials. Membrane damage is detected using the technique of analyzing capacitance-current peak changes obtained through rapid cyclic voltammetry measurements of a phospholipid self-assembled monolayer formed on a mercury film deposited onto a microfabricated platinum electrode after the interaction of a biomembrane-active species. To significantly improve wider usability of the screening technique, a compact, high-throughput screening platform was designed, integrating the monolayer-supporting microfabricated electrode into a microfluidic flow cell, with bespoke pumps used for precise, automated control of fluid flow. Chlorpromazine, a tricyclic antidepressant, and a citrate-coated 50 nm diameter gold nanomaterial (AuNM) were screened to successfully demonstrate the platform's viability for high-throughput screening. Chlorpromazine and the AuNM showed interactions with a 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) monolayer at concentrations in excess of 1 μmol dm-3. Biological validity of the electrochemically measured interaction of chlorpromazine with DOPC monolayers was confirmed through quantitative comparisons with HepG2 and A549 cytotoxicity assays. The platform also demonstrated desirable performance for high-throughput screening, with membrane interactions detected in <6 min per assay. Automation contributed to this significantly by reducing the required operating skill level when using the technique and minimizing fluid consumption.
AB - A high-throughput, automated screening platform has been developed for the assessment of biological membrane damage caused by nanomaterials. Membrane damage is detected using the technique of analyzing capacitance-current peak changes obtained through rapid cyclic voltammetry measurements of a phospholipid self-assembled monolayer formed on a mercury film deposited onto a microfabricated platinum electrode after the interaction of a biomembrane-active species. To significantly improve wider usability of the screening technique, a compact, high-throughput screening platform was designed, integrating the monolayer-supporting microfabricated electrode into a microfluidic flow cell, with bespoke pumps used for precise, automated control of fluid flow. Chlorpromazine, a tricyclic antidepressant, and a citrate-coated 50 nm diameter gold nanomaterial (AuNM) were screened to successfully demonstrate the platform's viability for high-throughput screening. Chlorpromazine and the AuNM showed interactions with a 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) monolayer at concentrations in excess of 1 μmol dm-3. Biological validity of the electrochemically measured interaction of chlorpromazine with DOPC monolayers was confirmed through quantitative comparisons with HepG2 and A549 cytotoxicity assays. The platform also demonstrated desirable performance for high-throughput screening, with membrane interactions detected in <6 min per assay. Automation contributed to this significantly by reducing the required operating skill level when using the technique and minimizing fluid consumption.
UR - http://www.scopus.com/inward/record.url?scp=85079426572&partnerID=8YFLogxK
U2 - 10.1063/1.5131562
DO - 10.1063/1.5131562
M3 - Article
C2 - 32113378
AN - SCOPUS:85079426572
SN - 0034-6748
VL - 91
JO - Review of Scientific Instruments
JF - Review of Scientific Instruments
IS - 2
M1 - 025002
ER -