Wenjiang Shen

Weighing of biomolecules, single cells and single nanoparticles in fluid

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.

Toward attogram mass measurements in solution with suspended nanochannel resonators.

Using suspended nanochannel resonators (SNRs), we demonstrate measurements of mass in solution with a resolution of 27 ag in a 1 kHz bandwidth, which represents a 100-fold improvement over existing suspended microchannel resonators and, to our knowledge, is the most precise mass measurement in liquid today. The SNR consists of a cantilever that is 50 microm long, 10 microm wide, and 1.3 microm thick, with an embedded nanochannel that is 2 microm wide and 700 nm tall. The SNR has a resonance frequency near 630 kHz and exhibits a quality factor of approximately 8000 when dry and when filled with water. In addition, we introduce a new method that uses centrifugal force caused by vibration of the cantilever to trap particles at the free end. This approach eliminates the intrinsic position dependent error of the SNR and also improves the mass resolution by increasing the averaging time for each particle.

Thermal conductivity of nanoporous bismuth thin films

The thermal conductivity of nanoporous Bi thin films has been experimentally determined. Samples are fabricated by a liquid phase deposition, and their thermal conductivities are measured by a differential 3ω method. Nanoporous Bi thin films exhibit an order-of-magnitude reduction in thermal conductivity compared to that of solid films, most likely the result of a reduction in phonon mean free path. When porous Bi films are exposed to a hydrogen plasma, thermal conductivity measurements reveal no variation with extent of porosity, while electrical conductivity is much more sensitive to porosity, suggesting the possibility of independent control of these two intrinsic properties.

Weighing nanoparticles in solution at the attogram scale

Significance Naturally occurring and engineered nanoparticles (e.g., exosomes, viruses, protein aggregates, and self-assembled nanostructures) have size- and concentration-dependent functionality, yet existing characterization methods in solution are limited for diameters below ∼50 nm. In this study, we developed a nanomechanical resonator that can directly measure the mass of individual nanoparticles down to 10 nm with single-attogram (10−18 g) precision, enabling access to previously difficult-to-characterize natural and synthetic nanoparticles. Physical characterization of nanoparticles is required for a wide range of applications. Nanomechanical resonators can quantify the mass of individual particles with detection limits down to a single atom in vacuum. However, applications are limited because performance is severely degraded in solution. Suspended micro- and nanochannel resonators have opened up the possibility of achieving vacuum-level precision for samples in the aqueous environment and a noise equivalent mass resolution of 27 attograms in 1-kHz bandwidth was previously achieved by Lee et al. [(2010) Nano Lett 10(7):2537–2542]. Here, we report on a series of advancements that have improved the resolution by more than 30-fold, to 0.85 attograms in the same bandwidth, approaching the thermomechanical noise limit and enabling precise quantification of particles down to 10 nm with a throughput of more than 18,000 particles per hour. We demonstrate the potential of this capability by comparing the mass distributions of exosomes produced by different cell types and by characterizing the yield of self-assembled DNA nanoparticle structures.

Controlling the adhesion force for electrostatic actuation of microscale mercury drop by physical surface modification

Under electrostatic actuation, mercury droplet can act as a contact and moving part in a microswitch system. In order to reduce the actuation voltage while keeping the electrical advantages of liquid-solid contact, the contact properties of mercury droplet on structured surfaces are investigated in this paper. Forces to actuate a mercury droplet on different structured surfaces are theoretically analyzed and experimentally tested. Both results confirm our claim that the adhesion forces of liquid metal droplets on a solid surface can be designed by physical modification of the surface. The criteria for detaching a mercury droplet from solid surface was predicted and verified by experimental results.

Fabrication and Characterization of an Integrated Microsystem for Protein Preconcentration and Sensing

We report on a fabrication and packaging process for a microsystem consisting of a mass-based protein detector and a fully integrated preconcentrator. Preconcentration of protein is achieved by means of a nanofluidic concentrator (NC), which takes advantage of fast nonlinear electroosmotic flow near a nanochannel-microchannel junction to concentrate charged molecules inside a volume of fluid on the order of 1 pL. Detection of preconcentrated protein samples is accomplished by passing them through a suspended microchannel resonator (SMR), which is a hollow resonant cantilever serially connected to the NC on the same device. The transit of a preconcentrated sample produces a transient shift in the cantilevers resonance frequency that is proportional to the density of the sample and, hence, the concentration of protein contained in it. A device containing both NC and SMR structures was produced using a novel fabrication process which simultaneously satisfies the separate packaging requirements of the two structures. The initial testing of this prototype device has demonstrated that the integrated SMR can accurately measure the concentration of a bovine serum albumin solution, that was preconcentrated using the integrated NC. Future improvements in the fabrication process will allow site-specific surface modification of the device and compatibility with separation methods, which will create opportunities for its application to immunoassays and universal detection.

Mercury droplet microswitch for re-configurable circuit interconnect

With electrostatic actuation, mercury droplets can act as moving and contact parts in a microswitch system. The physical stability of droplets in microscale and the low contact resistance between liquid and solid make the mercury switch an excellent candidate for the re-configurable circuit interconnect. Unlike previous micro-droplet switches, this paper reports, for the first time, a planar design and fabrication be compatible with underlying CMOS circuits. The driving voltage of the device is reduced from more than 150 V to around 80 V by surface modification technology. The response time for the switching is less than 1ms.

Electrostatic Side-Drive Rotary Stage on Liquid-Ring Bearing

We present an electrostatically actuated rotary stage featuring liquid rings, which serve as both mechanical bearings and electric connections between the rotor and the substrate. The liquid rings are formed by confining a liquid inside hydrophilic grooves and repelling it from the superhydrophobic surfaces outside the grooves. Made of a fluid, the liquid-ring bearing avoids the dry friction of the solid bearings, significantly improving the reliability. Formed as rings, it avoids the resistance of contact-angle hysteresis sliding over droplets, and hence dramatically reducing the static friction. Furthermore, surface tension facilitates the self-alignment of the rotor to the substrate and stator during the assembly and provides the stability against drift and shock during operation. Electrically, each liquid ring passes an independent electric signal, allowing a direct electrical path between the substrate and potential components on the rotor. A three-phase electrostatic rotary stage has been design, fabricated, and tested. The minimum torque to initiate the rotation is ~ 2.5 nN·m-hundreds of times smaller than droplet-based counterparts. The device has operated successfully by applying sequential voltages of 50 VDC between the rotor and the stators. The electric transmission has been verified by powering an LED on a rotating rotor. This is the first report of an electrostatically actuated rotating microdevice with a liquid bearing and a direct power transmission.

Combination of micro-scanning mirrors and multi-mode fibers for speckle reduction in high lumen laser projector applications

In high lumen laser projectors, it is required to use laser diodes coupled to multi-mode fibers (MMFs) to obtain a high power illumination module. In this paper, we have fabricated an electromagnetic micro-scanning mirror (EM-MSM), and we have firstly demonstrated a speckle reduction method by the combination of the EM-MSM and the MMF. With the help of a condenser lens, laser beams modulated and reflected from the EM-MSM are coupled into the MMF within its acceptance angle. Because the fast scanning behavior of the EM-MSM results in the phase modulation and mode coupling among the MMF guided modes, the light intensity field distributions at the exit aperture of the MMF are changing. During the charge-coupled device (CCD) integration time, the random speckle patterns are integrated and homogenized by the CCD camera, and hence speckle is reduced. By driving the EM-MSM in raster scan, the lowest compound speckle contrast ratio at 0.0794 is obtained, where the EM-MSM half scanning angles are 0.4 ° and the optical power loss is lower than 4.5%. The demonstrated technique is compact and can endure the high power of the laser module; thus, it has a promising potential in high lumen laser projector applications.

Electric lithography by electrochemical polymerization

We demonstrate a lithographic technique, electric lithography, in which conductive patterns on a mask are transferred to a substrate by applying an electric field to locally configure a resist layer sandwiched between the patterns and the substrate. Proof-of-concept pattern transfer experiments were carried out through electrochemical polymerization of pyrrole monomers dissolved in an aqueous electrolyte and 2,2′’-bithiophene monomers dissolved in a solid polymer electrolyte. By controlling the intensity and duration of the applied electric field on different mask patterns, we have also demonstrated that the electric lithography can create on-demand three-dimensional patterns in the resist.