I.E. Roslon
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Graphene-drum-enabled nanomotion detection can play an important role in probing life at the nanoscale. By combining micro- and nanomechanical systems with optics, nanomotion sensors bridge the gap between mechanics and cellular biophysics. They have allowed investigation of processes involved in metabolism, growth, and structural organization of a large variety of microorganisms, ranging from yeasts to bacterial cells. Using graphene drums, these processes can now be resolved at the single-cell level. In this Perspective, we discuss the key achievements of nanomotion spectroscopy and peek forward into the prospects for application of this single-cell technology in clinical settings. Furthermore, we discuss the steps required for implementation and look into applications beyond microbial sensing.
Probing nanoscale forces of nature in fluid
From pneumatics to biomechanics
Graphene, a single layer of carbon atoms, shows extreme strength and flexibility at the 2D limit of miniaturization. We have rationalized that graphene membranes are a perfect candidate to play the role of flexible support for detection of minute forces in nature, that are often hidden behind the veil of the environmental noise. Graphene owes its suitability to its ultimately thin nature, its low stiffness but simultaneously high tensile strength that prevents it from breaking under high tension. The limits of sensitivity can now be pushed further so that nanoscale forces can be measured in liquid - from pneumatic forces of attoliter volumes of gas, down to the level of single living bacteria.
In this thesis the motion of graphene membranes is studied under the influence of external forces. The motion is detected by a reflectometry setup devised for the study of optomechanical systems immersed in fluid. In Chapter 1 an introduction is given to the topic and the experimental methods are described. In Chapter 2, gases are pumped through a milled nanometer orifices in graphene membranes. The pneumatic interaction and the escape of the gasses through the nanometer scale pores is studied. In Chapter 3, we probe the nanomotion of single bacteria adhered to the surface of a graphene drum. The interplay between the processes occurring at cellular level and the motion of the suspended graphene with bacteria deposited on top is investigated. In Chapter 4, we study the signals obtained when motile bacteria cross a focused laser beam. We also find, that we can enhance the signal by patterning substrates to localise the bacteria close to the laser spot. Finally, in Chapter 5 we give prospects and outlooks, both on application of graphene drum enabled nanomotion sensing for rapid drug susceptibility testing, as well as on further research that might offer new insights into biological processes that can be held accountable for bacteria nanomotion. Furthermore, we discuss developments that would allow for further improvement of the current measurement system that go beyond bacterial sensing. ...
Graphene, a single layer of carbon atoms, shows extreme strength and flexibility at the 2D limit of miniaturization. We have rationalized that graphene membranes are a perfect candidate to play the role of flexible support for detection of minute forces in nature, that are often hidden behind the veil of the environmental noise. Graphene owes its suitability to its ultimately thin nature, its low stiffness but simultaneously high tensile strength that prevents it from breaking under high tension. The limits of sensitivity can now be pushed further so that nanoscale forces can be measured in liquid - from pneumatic forces of attoliter volumes of gas, down to the level of single living bacteria.
In this thesis the motion of graphene membranes is studied under the influence of external forces. The motion is detected by a reflectometry setup devised for the study of optomechanical systems immersed in fluid. In Chapter 1 an introduction is given to the topic and the experimental methods are described. In Chapter 2, gases are pumped through a milled nanometer orifices in graphene membranes. The pneumatic interaction and the escape of the gasses through the nanometer scale pores is studied. In Chapter 3, we probe the nanomotion of single bacteria adhered to the surface of a graphene drum. The interplay between the processes occurring at cellular level and the motion of the suspended graphene with bacteria deposited on top is investigated. In Chapter 4, we study the signals obtained when motile bacteria cross a focused laser beam. We also find, that we can enhance the signal by patterning substrates to localise the bacteria close to the laser spot. Finally, in Chapter 5 we give prospects and outlooks, both on application of graphene drum enabled nanomotion sensing for rapid drug susceptibility testing, as well as on further research that might offer new insights into biological processes that can be held accountable for bacteria nanomotion. Furthermore, we discuss developments that would allow for further improvement of the current measurement system that go beyond bacterial sensing.
The resonance frequency of ultra-thin layered nanomaterials changes nonlinearly with the tension induced by the pressure from the surrounding gas. Although the dynamics of pressurized nanomaterial membranes have been extensively explored, recent experimental observations show significant deviations from analytical predictions. Here, we present a multi-mode continuum model that captures the nonlinear pressure-frequency response of pre-tensioned membranes undergoing large deflections. We validate the model using experiments conducted on polysilicon nanodrums excited opto-thermally and subjected to pressure changes in the surrounding medium. We demonstrate that considering the effect of pressure on the nanodrum tension is not sufficient for determining the resonance frequencies. In fact, it is essential to also account for the change in the membrane’s shape in the pressurized configuration, the mid-plane stretching, and the contributions of higher modes to the mode shapes. Finally, we show how the presented high-frequency mechanical characterization method can serve as a fast and contactless method for determining Young’s modulus of ultra-thin membranes.
Bacteria that are resistant to antibiotics present an increasing burden on healthcare. To address this emerging crisis, novel rapid antibiotic susceptibility testing (AST) methods are eagerly needed. Here, we present an optical AST technique that can determine the bacterial viability within 1 h down to a resolution of single bacteria. The method is based on measuring intensity fluctuations of a reflected laser focused on a bacterium in reflective microwells. Using numerical simulations, we show that both refraction and absorption of light by the bacterium contribute to the observed signal. By administering antibiotics that kill the bacteria, we show that the variance of the detected fluctuations vanishes within 1 h, indicating the potential of this technique for rapid sensing of bacterial antibiotic susceptibility. We envisage the use of this method for massively parallelizable AST tests and fast detection of drug-resistant pathogens.
Motion is a key characteristic of every form of life1. Even at the microscale, it has been reported that colonies of bacteria can generate nanomotion on mechanical cantilevers2, but the origin of these nanoscale vibrations has remained unresolved3,4. Here, we present a new technique using drums made of ultrathin bilayer graphene, where the nanomotion of single bacteria can be measured in its aqueous growth environment. A single Escherichia coli cell is found to generate random oscillations with amplitudes of up to 60 nm, exerting forces of up to 6 nN to its environment. Using mutant strains that differ by single gene deletions that affect motility, we are able to pinpoint the bacterial flagella as the main source of nanomotion. By real-time tracing of changes in nanomotion on administering antibiotics, we demonstrate that graphene drums can perform antibiotic susceptibility testing with single-cell sensitivity. These findings deepen our understanding of processes underlying cellular dynamics, and pave the way towards high-throughput and parallelized rapid screening of the effectiveness of antibiotics in bacterial infections with graphene devices.
Porous, atomically thin graphene membranes have interesting properties for filtration and sieving applications. Here, graphene membranes are used to pump gases through nanopores using optothermal forces, enabling the study of gas flow through nanopores at frequencies above 100 kHz. At these frequencies, the motion of graphene is closely linked to the dynamic gas flow through the nanopore and can thus be used to study gas permeation at the nanoscale. By monitoring the time delay between the actuation force and the membrane mechanical motion, the permeation time-constants of various gases through pores with diameters from 10–400 nm are shown to be significantly different. Thus, a method is presented for differentiating gases based on their molecular mass and for studying gas flow mechanisms. The presented microscopic effusion-based gas sensing methodology provides a nanomechanical alternative for large-scale mass-spectrometry and optical spectrometry based gas characterisation methods.
Diffusion Mechanism of Li Argyrodite Solid Electrolytes for Li-Ion Batteries and Prediction of Optimized Halogen Doping
The Effect of Li Vacancies, Halogens, and Halogen Disorder
Using density functional theory molecular dynamics simulations, the origin of the Li-ion conductivity in argyrodite solid electrolytes is investigated. The simulations show that besides Li-ion vacancies in Li6PS5Cl and Li6PS5Br, the influence of halogen atoms on their local surroundings also plays an important role in Li-ion diffusion. The difference in Li-ion conductivity between Li6PS5Cl and Li6PS5I, which is several orders of magnitude, is caused by the distribution of the halogen ions over the available crystallographic sites. This suggests that altering the halogen distribution in Li argyrodites during synthesis could increase the Li-ion conductivity of these materials. For Li6PS5Cl, the simulations predict an optimal Cl distribution of 1:3 over sites 4a and 4c, resulting in a Li-ion conductivity that is 2 times larger than that of the currently prepared materials. On the basis of these results, simulations were performed on Li5PS4X2 (X = Cl, Br, or I), which show Li-ion conductivities similar to those of Li6PS5Cl and Li6PS5Br, suggesting that the Li5PS4X2 compounds are interesting new compositions for solid state electrolytes.
Unravelling Li-Ion Transport from Picoseconds to Seconds
Bulk versus Interfaces in an Argyrodite Li6PS5Cl-Li2S All-Solid-State Li-Ion Battery
One of the main challenges of all-solid-state Li-ion batteries is the restricted power density due to the poor Li-ion transport between the electrodes via the electrolyte. However, to establish what diffusional process is the bottleneck for Li-ion transport requires the ability to distinguish the various processes. The present work investigates the Li-ion diffusion in argyrodite Li6PS5Cl, a promising electrolyte based on its high Li-ion conductivity, using a combination of 7Li NMR experiments and DFT based molecular dynamics simulations. This allows us to distinguish the local Li-ion mobility from the long-range Li-ion motional process, quantifying both and giving a coherent and consistent picture of the bulk diffusion in Li6PS5Cl. NMR exchange experiments are used to unambiguously characterize Li-ion transport over the solid electrolyte-electrode interface for the electrolyte-electrode combination Li6PS5Cl-Li2S, giving unprecedented and direct quantitative insight into the impact of the interface on Li-ion charge transport in all-solid-state batteries. The limited Li-ion transport over the Li6PS5Cl-Li2S interface, orders of magnitude smaller compared with that in the bulk Li6PS5Cl, appears to be the bottleneck for the performance of the Li6PS5Cl-Li2S battery, quantifying one of the major challenges toward improved performance of all-solid-state batteries.