Weighing nanoparticles and viruses using suspended nanochannel resonators

Measurement of the Average Mass of Proteins Adsorbed to a Nanoparticle by Using a Suspended Microchannel Resonator

We demonstrate the measurement of mass, density, and size of cells and nanoparticles using suspended microchannel resonators. The masses of individual particles are quantified as transient frequency shifts, while the particles transit a microfluidic channel embedded in the resonating cantilever. Mass histograms resulting from these data reveal the distribution of a population of heterogeneously sized particles. Particle density is inferred from measurements made in different carrier fluids since the frequency shift for a particle is proportional to the mass difference relative to the displaced solution. We have characterized the density of polystyrene particles, Escherichia coli, and human red blood cells with a resolution down to 10−4g∕cm3.

Suspended microchannel resonator (SMR) has been demonstrated as a versatile technique, allowing to measure mechanical, morphological or even optical properties of cells. However, physical properties of cells may substantially change depending on the chemical composition of the suspension medium. Therefore, it is essential developing novel multiparametric techniques able to provide a complete understanding of the biological samples by characterizing also the liquid in which the cells are suspended. In this work we both theoretically and experimentally introduce a novel electro-mechanical sensing technique using SMR devices with integrated electrodes that allow measuring different physicochemical properties of the liquid sample as thermal conductivity, dielectric constant, electrical conductivity or even concentration of ions. These measured liquid properties can ultimately be used to complement other typical SMR measurements, such as mass. Moreover, we show that this electro-mechanical approach can be also used as a transduction method and as a way of tuning the mechanical resonance frequency.

Cell growth comprises changes in both mass and volume--two processes that are distinct, yet coordinated through the cell cycle. Understanding this relationship requires a means for measuring each of the cell's three basic physical parameters: mass, volume, and the ratio of the two, density. The suspended microchannel resonator weighs single cells with a precision in mass of 0.1% for yeast. Here we use the suspended microchannel resonator with a Coulter counter to measure the mass, volume, and density of budding yeast cells through the cell cycle. We observe that cell density increases prior to bud formation at the G1/S transition, which is consistent with previous measurements using density gradient centrifugation. To investigate the origin of this density increase, we monitor relative density changes of growing yeast cells. We find that the density increase requires energy, function of the protein synthesis regulator target of rapamycin, passage through START (commitment to cell division), and an intact actin cytoskeleton. Although we focus on basic cell cycle questions in yeast, our techniques are suitable for most nonadherent cells and subcellular particles to characterize cell growth in a variety of applications.

A measurement criterion for accurate mass detection using vibrating suspended microchannel resonators

The use of a second electrospray nebuliser has proved to be highly successful for exact mass measurement during high-performance liquid chromatography/Fourier transform ion cyclotron resonance mass spectrometry (HPLC/FTICRMS). Much improved accuracy and precision of mass measurement were afforded by the introduction of the internal calibration solution, thus overcoming space charge issues due to the lack of control over relative ion abundances of the species eluting from the HPLC column. Further, issues of suppression of ionisation, observed when using a T-piece method, are addressed and this simple system has significant benefits over other more elaborate approaches providing data that compares very favourably with these other approaches. The technique is robust, flexible and transferable and can be used in conjunction with HPLC, infusion or flow injection analysis (FIA) to provide constant internal calibration signals to allow routine, accurate and precise mass measurements to be recorded.

Nanomechanical resonators enable the measurement of mass with extraordinary sensitivity. Previously, samples as light as 7 zeptograms (1 zg = 10(-21) g) have been weighed in vacuum, and proton-level resolution seems to be within reach. Resolving small mass changes requires the resonator to be light and to ring at a very pure tone-that is, with a high quality factor. In solution, viscosity severely degrades both of these characteristics, thus preventing many applications in nanotechnology and the life sciences where fluid is required. Although the resonant structure can be designed to minimize viscous loss, resolution is still substantially degraded when compared to measurements made in air or vacuum. An entirely different approach eliminates viscous damping by placing the solution inside a hollow resonator that is surrounded by vacuum. Here we demonstrate that suspended microchannel resonators can weigh single nanoparticles, single bacterial cells and sub-monolayers of adsorbed proteins in water with sub-femtogram resolution (1 Hz bandwidth). Central to these results is our observation that viscous loss due to the fluid is negligible compared to the intrinsic damping of our silicon crystal resonator. The combination of the low resonator mass (100 ng) and high quality factor (15,000) enables an improvement in mass resolution of six orders of magnitude over a high-end commercial quartz crystal microbalance. This gives access to intriguing applications, such as mass-based flow cytometry, the direct detection of pathogens, or the non-optical sizing and mass density measurement of colloidal particles.

A cantilever biosensor based on a gap method for detecting Escherichia coli in real time

Cell size, measured as either volume or mass, is a fundamental indicator of cell state. Far more tightly regulated than size is density, the ratio between mass and volume, which can be used to distinguish between cell populations even when volume and mass appear to remain constant. Here we expand upon a previous method for measuring cell density involving a suspended microchannel resonator (SMR). We introduce a new device, the dual SMR, as a high-precision instrument for measuring single-cell mass, volume, and density using two resonators connected by a serpentine fluidic channel. The dual SMR designs considered herein demonstrate the critical role of channel geometry in ensuring proper mixing and damping of pressure fluctuations in microfluidic systems designed for precision measurement. We use the dual SMR to compare the physical properties of two well-known cancer cell lines: human lung cancer cell H1650 and mouse lymphoblastic leukemia cell line L1210.

We report an $\textit{in situ}$ mass measurement of approximately-$4.7{\text -}\mu$m-diameter, optically levitated microspheres with an electrostatic co-levitation technique. The mass of a trapped, charged microsphere is measured by holding its axial (vertical) position fixed with an optical feedback force, under the influence of a known electrostatic force. A mass measurement with $1.8\%$ systematic uncertainty is obtained by extrapolating to the electrostatic force required to support the microsphere against gravity in the absence of optical power. In three cases, the microspheres are recovered from the trap on a polymer-coated silicon beam and imaged with an electron microscope to measure their radii. The simultaneous precision characterization of the mass and radius of individual microspheres implies a density of $1.55\pm0.08~$g/cm$^3$. The ability to recover individual microspheres from an optical trap opens the door to further diagnostics.

Yellow straggler stars (YSSs) fall above the subgiant branch in optical color–magnitude diagrams (CMDs), between the blue stragglers and the red giants. YSSs may represent a population of evolved blue stragglers, but none have the direct and precise mass and radius measurements needed to determine their evolutionary states and formation histories. Here we report the first asteroseismic mass and radius measurements of such a star, the yellow straggler S1237 in the open cluster M67. We apply asteroseismic scaling relations to a frequency analysis of the Kepler K2 light curve and find a mass of 2.9 ± 0.2 M ⊙ and a radius of 9.2 ± 0.2 R ⊙. This is more than twice the mass of the main-sequence turnoff in M67, suggesting that S1237 is indeed an evolved blue straggler. S1237 is the primary in a spectroscopic binary. We update the binary orbital solution and use spectral energy distribution fitting to constrain the CMD location of the secondary star. We find that the secondary is likely an upper main-sequence star near the turnoff, but a slightly hotter blue straggler companion is also possible. We then compare the asteroseismic mass of the primary to its mass from CMD fitting, finding that the photometry implies a mass and radius more than 2σ below the asteroseismic measurement. Finally, we consider formation mechanisms for this star and suggest that S1237 may have formed from dynamical encounters resulting in stellar collisions or a binary merger.

We are going to propose a novel total body composition measurement device which is based on Bioelectrical-Impedance Analysis (BIA) which is temperature compensated with the aid of a computer. We are making use of aluminium electrodes for this purpose. Proximal electrodes are used to measure the voltage distant electrodes of right head and foot with an excitation current of 0.8mA at 50 KHz are used for initiation. This work signifies low power consumption and precise measurement results. 50 KHz of higher frequency is needed so that it can easily penetrate the cell membrane. Our work has adopted multi frequency serial current to measure intra and extra cellular fluid and hence to have précised accuracy. Analog blocks include Band Pass Filter (BPF), Full Wave Rectifier (FWR) etc. Digital circuits include micom and memory. Total body composition measurement includes precise measurement of Fat mass (FM), Fat Free Mass (FFM) and Total Body Water (TBW). These values are compared with skin fold thickness measurements measured by digital caliper of 200mm thickness and results are tabulated and analyzed. With the intension of producing anti obsessed society to minimize health risks this body composition analyzer is produced.

NGC 4258 is an SABbc Seyfert galaxy, located at a distance of $7.2 \pm 0.3$ Mpc. This object is well known by its nearly edge-on molecular nuclear disc, located between 0.16 and 0.28 pc from the nucleus, whose H$_2$O maser emission allows a very precise measurement of the central supermassive black hole mass ($M_{\bullet}(maser) = 3.78 \pm 0.01 \times 10^7$ Mo). We analyse the emission line properties and the stellar kinematics in a data cube of the central region of NGC 4258, obtained, in the K band, with the Near-Infrared Integral Field Spectrograph, at the Gemini-north telescope. The nuclear spectrum, after the starlight subtraction, shows only the H$_2 \lambda 2.1218$ $\mu$m and Br$\gamma$ emission lines, the latter having a broad component with FWHM$_{Br\gamma}(broad) = 1600 \pm 29$ km s$^{-1}$. The spatial morphology and kinematics of the H$_2 \lambda 2.1218$ $\mu$m line are consistent with a rotating molecular disc around the supermassive black hole, with an upper limit for its diameter of 15.7 pc. The inner radio jet in this object is, in projection, almost perpendicular to the H$_2$ emitting disc detected in this work, and also to the H$_2$O maser emitting disc. The main features of the maps of the stellar kinematic parameters are well reproduced by a model of a thin rotating stellar circular disc. The supermassive black hole mass provided by this dynamical modelling ($M_{\bullet}(disc) = 2.8 \pm 1.0 \times 10^7$ Mo) is compatible, at 1$\sigma$ level, with the precise measurement resulting from the H$_2$O maser emission.

The masses of charged atoms and molecules were first investigated by laterally dispersive sector field mass analyzers, which early on already achieved high mass resolving powers. Equally, high mass resolving powers were achieved by time-of-flight mass analyzers during the last decades. These measurements became possible when fast and precise electronic circuitries became available. Such techniques have been developed and used extensively for the mass analysis of short-lived nuclei, whose mass values reveal insight in processes that describe the formation of elements in star explosions. Precise mass determinations of short-lived ions have been performed for energetic ions in large accelerator storage rings as well as for low-energy ions in time-of-flight mass spectrographs with long flight paths. Similarly, precise mass measurements can also be performed for molecular ions that help to reveal the structure of molecules. In case of very high mass resolving powers, the mass determination of molecular ions can be so high that the measured ion mass directly reveals the molecule’s sum formula.

In Penning traps charged particles are subject to a strong axial magnetic field and a weak electrostatic quadrupole field, which makes the particles moving with three independent frequencies. The quadrupole field can be generated either by using hyperboloidal or a set of cylindrical electrodes. A cyclotron frequency measurement gives access to an accurate value of the ion mass. This can be performed either by the determination of images currents in a ring electrode or by using a time-of-flight method after excitation of the ion motion. In 1970 Hans Dehmelt et al. measured the g-factors of a free electron and positron as well as their masses using a Penning trap. This lead to a shared Nobel Prize in Physics in 1989. These measurements were the overture to a large number of fundamental experiments. The experimental g-factor was compared to the value predicted by QED, which indirectly gives the fine structure constant α at an uncertainty of 4 ppb. The obvious question is to what extent the g-factor is changed when the electron is bound in a hydrogen-like ion. To obtain an answer a dedicated set of traps was constructed by the GSI-Mainz collaboration. Recently, a different way of calculating α was proposed. It is based on laser photon recoil experiments and may result in an even a more accurate value of α that is independent of QED. This a method requires very accurate mass values of the electron, the proton and 133 C s . Precise mass and g-factor measurements offer CPT-tests. Accurate mass values of 3 H and 3 He, i.e. the Q-value of the 3 H decay, may enter in future experiments on the beta spectrum of 3 H searching for a finite rest mass of the electron antineutrino. The mass difference between 76 Ge and 76 Se is indispensable in the analysis of the data searching for the standard model violating neutrinoless double beta decay of 76 Ge. Accurate masses of 28 Si and 197 Au are needed in efforts for a new definition of the kilogram based on atomic quantities.