Mass Detection with Nonlinear Nanomechanical Resonator

Nanomechanical resonators having small mass, high resonance frequency and low damping rate are widely employed as mass detectors. We study the performances of such a detector when the resonator is driven into a region of nonlinear oscillations. We predict theoretically that in this region the system acts as a phase-sensitive mechanical amplifier. This behavior can be exploited to achieve noise squeezing in the output signal when homodyne detection is employed for readout. We show that mass sensitivity of the device in this region may exceed the upper bound imposed by thermomechanical noise upon the sensitivity when operating in the linear region. On the other hand, we show that the high mass sensitivity is accompanied by a slowing down of the response of the system to a change in the mass

Portable and integrated microfluidic flow control system using off-the-shelf components towards organs-on-chip applications

Organ-on-a-chip (OoC) devices require the precise control of various media. This is mostly done using several fluid control components, which are much larger than the typical OoC device and connected through fluidic tubing, i.e., the fluidic system is not integrated, which inhibits the system’s portability. Here, we explore the limits of fluidic system integration using off-the-shelf fluidic control components. A flow control configuration is proposed that uses a vacuum to generate a fluctuation-free flow and minimizes the number of components used in the system. 3D printing is used to fabricate a custom-designed platform box for mounting the chosen smallest footprint components. It provides flexibility in arranging the various components to create experiment-specific systems. A demonstrator system is realized for lung-on-a-chip experiments. The 3D-printed platform box is 290 mm long, 240 mm wide and 37 mm tall. After integrating all the components, it weighs 4.8 kg. The system comprises of a switch valve, flow and pressure controllers, and a vacuum pump to control the diverse media flows. The system generates liquid flow rates ranging from 1.5 μ Lmin - 1 to 68 μ Lmin - 1 in the cell chambers, and a cyclic vacuum of 280 mbar below atmospheric pressure with 0.5 Hz frequency in the side channels to induce mechanical strain on the cells-substrate. The components are modular for easy exchange. The battery operated platform box can be mounted on either upright or inverted microscopes and fits in a standard incubator. Overall, it is shown that a compact integrated and portable fluidic system for OoC experiments can be constructed using off-the-shelf components. For further down-scaling, the fluidic control components, like the pump, switch valves, and flow controllers, require significant miniaturization while having a wide flow rate range with high resolution.</p

Comprehensive characterization of molecular interactions based on nanomechanics

Molecular interaction is a key concept in our understanding of the biological mechanisms of life. Two physical properties change when one molecular partner binds to another. Firstly, the masses combine and secondly, the structure of at least one binding partner is altered, mechanically transducing the binding into subsequent biological reactions. Here we present a nanomechanical micro-array technique for bio-medical research, which not only monitors the binding of effector molecules to their target but also the subsequent effect on a biological system in vitro. This label-free and real-time method directly and simultaneously tracks mass and nanomechanical changes at the sensor interface using micro-cantilever technology. To prove the concept we measured lipid vesicle (approximately 748*10(6) Da) adsorption on the sensor interface followed by subsequent binding of the bee venom peptide melittin (2840 Da) to the vesicles. The results show the high dynamic range of the instrument and that measuring the mass and structural changes simultaneously allow a comprehensive discussion of molecular interactions

Mass measurement of graphene using quartz crystal microbalances

Current wafer-scale fabrication methods for graphene-based electronics and sensors involve the transfer of single-layer graphene by a support polymer. This often leaves some polymer residue on the graphene, which can strongly impact its electronic, thermal, and mechanical resonance properties. To assess the cleanliness of graphene fabrication methods, it is thus of considerable interest to quantify the amount of contamination on top of the graphene. Here, we present a methodology for direct measurement of the mass of the graphene sheet using quartz crystal microbalances (QCM). By monitoring the QCM resonance frequency during removal of graphene in an oxygen plasma, the total mass of the graphene and contamination is determined with sub-graphene-monolayer accuracy. Since the etch-rate of the contamination is higher than that of graphene, quantitative measurements of the mass of contaminants below, on top, and between graphene layers are obtained. We find that polymer-based dry transfer methods can increase the mass of a graphene sheet by a factor of 10. The presented mass measurement method is conceptually straightforward to interpret and can be used for standardized testing of graphene transfer procedures in order to improve the quality of graphene devices in future applications

Experimental and Computational Characterization of Biological Liquid Crystals: A Review of Single-Molecule Bioassays

Quantitative understanding of the mechanical behavior of biological liquid crystals such as proteins is essential for gaining insight into their biological functions, since some proteins perform notable mechanical functions. Recently, single-molecule experiments have allowed not only the quantitative characterization of the mechanical behavior of proteins such as protein unfolding mechanics, but also the exploration of the free energy landscape for protein folding. In this work, we have reviewed the current state-of-art in single-molecule bioassays that enable quantitative studies on protein unfolding mechanics and/or various molecular interactions. Specifically, single-molecule pulling experiments based on atomic force microscopy (AFM) have been overviewed. In addition, the computational simulations on single-molecule pulling experiments have been reviewed. We have also reviewed the AFM cantilever-based bioassay that provides insight into various molecular interactions. Our review highlights the AFM-based single-molecule bioassay for quantitative characterization of biological liquid crystals such as proteins

Resonating nanomechanical microcantilevers for quantitative biological measurements in liquid

Nanomechanical cantilevers have been proved as extremely sensitive time resolved mass and surface stress sensors. Recent demonstration of zepto gram (10−21 grams) sensitivity in vacuum and label free detection of human RNA biomarkers in the total background of cellular RNA at pM range are the unprecedented achievements with these sensors. However, using them as mass sensors in liquid has always been a great challenge. This thesis describes the successful attempt in resonating microcantilevers in liquid and using them as quantitative mass sensors for biological applications. Futhermore, simultaneous measurement of mass sensing and surface stress sensing provides a unique system which can detect multistep and multiprocess systems in biology without any labels. The Instrument: Chapter 1 describes the present status of these sensors in various fields. A review of interesting experiments performed by various researchers is presented. In Chapter 2 a detailed description of the setup which uses a tiny liquid chamber of 6 μl to hold a microcantilever array is given. Working principles of various parts and mathematical description of basic operating modes are also discussed. Importance of laser beam diameter for detection and a model test result of simultaneous stress and mass sensing are given in the results section. Higher modes of vibration increase mass sensitivity: Operating the microcantilevers at higher modes increases mass sensitivity by at least two orders of magnitude. This is demonstrated by uniformly deposited gold layers on the cantilevers (see Chapter 3). A sensitivity increase of 940 ag/Hz/μm2 at mode 1 to 8.6 ag/Hz/μm2 at mode 7 under ambient conditions has been proved. The limitation of mass load with cantilever thickness is dealt in detail. Resonating microcantilevers in liquid: In Chapter 4, a frequency spectrum with clear well resolved resonance peaks for 16 flexural modes of vibration in liquid is presented. The increase in quality factor with mode number is shown. The predicted frequency values from theoretical models and the estimated added apparent mass due to liquid on the resonating cantilever at various modes are compared. The independent effect of density and viscosity at various modes of vibration is discussed in Chapter 5. A distinguishable difference between peak frequency and eigen frequency is revealed in the plots. Mass measurement of latex beads in liquid: A test system based on binding of biotin labeled latex beads to the streptavidin functionalized cantilever for measurement of mass sensitivity is described in Chapter 6. The increase in mass sensitivity at higher modes even in liquids is clearly demonstrated. A total of 7 ng was detected with a resolution of 1 ng. Quantitative biological measurements: In Chapter 7 quantitative measurement on real time biological system is presented. A new functionalization technique based on inkjet spotting was used to immobilize 2D crystals of reconstituted FhuA transmembrane proteins. FhuA functionalized cantilevers were found sensitive to detect the binding of ligands T5 phage virus particles (10−17g) and ferrichrome molecules (700 Da). Detecting multistep and multivariant biological system: An experiment demonstrating the capability of the system to perform simultaneous mass sensing and stress sensing is described in Chapter 8. The mass measurement plots reveal that only monolayer formation of lipid vesicles occurs. A multistep experiment with initial vesicle adsorption and subsequent binding of bee venom protein (melittin) demonstrates measurements in different mass ranges. Simultaneously, tensile stress on the cantilever due to vesicle adsorption and the subsequent compressive stress owing to the pore formation of melittin in the immobilized vesicles are observed in the deflection plot. Finally Chapter 9 concludes summarizing all the results obtained

Resonating modes of vibrating microcantilevers in liquid

A study of nanomechanical cantilevers vibrating at various resonating modes in liquid is presented. Resonant frequency spectrum with 16 well resolved flexural modes is obtained. The quality factor increased from 1 at mode 1 to 30 at mode 16. The theoretical estimate of eigenfrequency using the Elmer-Dreier model [F.-J. Elmer and M. Dreier, J. Appl. Phys. 81, 12 (1997)] and Sader`s extended viscous model [C. A. Van Eysden and J. E. Sader, J. Appl. Phys. 101, 044908 (2007)] matched well with the experimental data. The apparent mass of the liquid comoved by the oscillating cantilevers decreased asymptotically with mode number