E. ROSTOVA¹, S.K. SEKATSKII¹, G. DIETLER<sup>1

1</sup>École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland Laboratoire de physique de la matière vivante

According to reviews on antimicrobial resistance, each year around 700’000 people die of infections caused by drug resistant bacteria. The spread of the antimicrobial resistance caused by a substantial misuse of antibiotics is a growing public health concern worldwide. Prescription drug abuse is likely provoked by unknown drug action mechanisms, which are challenging to discover by available technologies. Therefore, an efficient technique is needed for measurements of drug binding interactions.

Drug binding kinetics on living cells can be measured by a biosensor based on photonic crystal surface waves. In the biosensor, two optical surface waves are supported by a specially designed photonic crystal consisting of dielectric layers with different refractive indices. When the sample attaches on the photonic crystal surface, the refractive index of the medium adjacent to the surface increases, and the change of the excitation conditions of the surface waves is monitored by the camera. Sufficient sensitivity of the biosensor is achieved due to a deeper wave penetration into the sample compared to typical optical biosensors.

Using this biosensor, we studied binding kinetics of mono- and polyclonal antibodies against bacterial lipopolysaccharides to living gram-negative bacteria Escherichia coli DH5α. High sensor sensitivity due to a specially designed photonic crystal permits to observe binding of the antibodies at a concentration of 1.25 μg/ml. The data analysis reveals specific binding with the dissociation constant (KD = 6.2 3.4 nM) for the monoclonal antibodies.

Qualitative kinetic information collected in real time on living cells will certainly accelerate and optimize screening of drug candidates. The photonic crystal-based biosensor can serve as a “control unit” in antibody production for rapid selection of the best isoform based on its kinetic properties. Also cancer cells and various drugs are our next focus. Ultimately, the biosensor can be employed to study binding of drugs together with a viability test, eventually leading to the identification of currently unclear mechanisms of drug action.