Monitoring of individual bacteria using electro-photonic traps

Abstract

Antimicrobial resistance (AMR) describes the ability of bacteria to become immune to antimicrobial treatments. Current testing for AMR is based on culturing methods that are very slow because they assess the average response of billions of bacteria. In principle, if tests were available that could assess the response of individual bacteria, they could be much faster. Here, we propose an electro-photonic approach for the analysis and the monitoring of susceptibility at the single-bacterium level. Our method employs optical tweezers based on photonic crystal cavities for the trapping of individual bacteria. While the bacteria are trapped, antibiotics can be added to the medium and the corresponding changes in the optical properties and motility of the bacteria be monitored via changes of the resonance wavelength and transmission. Furthermore, the proposed assay is able to monitor the impedance of the medium surrounding the bacterium, which allows us to record changes in metabolic rate in response to the antibiotic challenge. For example, our simulations predict a variation in measurable electrical current of up to 40% between dead and live bacteria. The proposed platform is the first, to our knowledge, that allows the parallel study of both the optical and the electrical response of individual bacteria to antibiotic challenge. Our platform opens up new lines of enquiry for monitoring the response of bacteria and it could lead the way towards the dissemination of a new generation of antibiogram study, which is relevant for the development of a point-of-care AMR diagnostics.

Nanophotonics for bacterial detection and antimicrobial susceptibility testing

“…Importantly, we note that the advantage of using some of these indicators alternative to growth is also supported by other findings which do not necessarily use photonics, such as microfluidic techniques [25,119,133,134], AFM cantilever deflection [24,120,135] or electrochemical platforms [136][137][138]. For example, bacterial metabolism drives ionexchange across the membrane, so we see the measurement of electrical impedance at the single-cell level as a very promising method that could be added to the toolkit [90,136]. These observations suggest that a synergistic approach between different domains is desirable, as it might be able to provide even greater insight and meet important needs that still pose challenges.…”

“…Antibiotic susceptibility is a multidimensional problem that can only be solved with a multiparameter approach. Several techniques have already recognized this need by measuring multiple responses in parallel, for example, morphology in conjunction with motility [25] or single-cell division [132,133], electrical impedance with motility [90] or bacterial division [138], as well as growth and motility [118].…”

“…The idea builds on the "electrophotonics" principle we introduced earlier, whereby the judicious doping of silicon allows conducting electrochemical measurements on the surface of an optical waveguide structure in a high-Q silicon microring resonator [88,89]. Using similar principles, we considered an arrangement that combines silicon photonic crystal cavities for optical trapping with doped regions for conducting impedance measurements [90]. A schematic of a single trap is shown in Figure 4(c).…”

Novel Micro-Nano Optoelectronic Biosensor for Label-Free Real-Time Biofilm Monitoring

“…Integrated optical devices have also been used for single bacteria analysis with label-free techniques [20]. In particular, resonant cavities are able to trap and identify single bacteria through the changes of the resonance response [21,22]. Emerging studies with a label-free optical-based approach have demonstrated real-time monitoring of cell attachment and the development of bacteria on the sensor surface [23].…”

Optical Forces in Silicon Nanophotonics and Optomechanical Systems: Science and Applications

“…However, this measurement approach cannot differentiate specific bacteria strains due to the overlapped refractive index variation of the bacteria. Conteduca et al used the silicon photonic crystal cavity with metal electrodes to trap single bacterium for antimicrobial resistance studies [69]. In addition to optical properties (transmission and resonance shift), the impedance of the surrounding medium is monitored, which is correlated to the metabolic rate in response to antibiotics.…”