Jens-Christian Meiners

Topologic mixing on a microfluidic chip

Mixing two liquids on a microfluidic chip is notoriously hard because the small dimensions and velocities on the chip effectively prevent turbulence. We present a topological mixing scheme that exploits the laminarity of the flow to repeatedly fold the flow and exponentially increase the concentration gradients to obtain fast and efficient mixing by diffusion. It is based on helical flow channels with opposite chiralities that split, rotate, and recombine the fluid stream in a topology reminiscent of a series of Mobius bands. This geometry is realized in a simple six-stage, two-layer elastomer structure with a footprint of 400 μm×300 μm per stage that mixes two solutions efficiently at Reynolds numbers between 0.1 and 2. This represents more than an order of magnitude reduction in the size of microfluidic mixers that can be manufactured in standard multilayer soft lithography techniques.

Near field microscopy and lithography with uncoated fiber tips: a comparison

We show that lateral resolution well beyond 100 nm can be obtained in scanning near-field optical microscopy (SNOM) using uncoated glass fiber tips in the internal reflection mode. Exposure of a photosensitive layer through the tip of a tapered optical fiber reveals that the illuminated area underneath the fiber tip is far larger than the best resolution obtained in microscopy. This finding points to the importance of the particular beam path in an internal reflection mode SNOM experiment. Lithographic experiments with metal coated fiber tips show that in this case, the light field emitted by the tip is indeed confined to an area below 100 nm.

Multiplexed hydraulic valve actuation using ionic liquid filled soft channels and Braille displays

Pneumatic actuation with multilayer soft lithography enables operation of up to thousands of valves in parallel using far fewer control lines. However, it is dependent on macroscopic switches and external pressure sources that require interconnects and limit portability. The authors present a more portable and multiplexed valve actuation strategy that uses a grid of mechanically actuated Braille pins to hydraulically, rather than pneumatically, deform elastic actuation channels that act as valves. Experimental and theoretical analyses show that the key to reliable operation of the hydraulic system is the use of nonvolatile ionic liquids as the hydraulic fluid.

Stretching submicron biomolecules with constant-force axial optical tweezers.

Optical tweezers have become powerful tools to manipulate biomolecular systems, but are increasingly difficult to use when the size of the molecules is <1 microm. Many important biological structures and processes, however, occur on the submicron length scale. Therefore, we developed and characterized an optical manipulation protocol that makes this length scale accessible by stretching the molecule in the axial direction of the laser beam, thus avoiding limiting artifacts from steric hindrances from the microscope coverslip and other surface effects. The molecule is held under constant mechanical tension by a combination of optical gradient forces and backscattering forces, eliminating the need for electronic feedback. We demonstrate the utility of this method through a measurement of the force-extension relationship of a 1298 bp ds-DNA molecule.

Chemically functionalized surfaces from ultrathin block‐copolymer films

Supramolecular self‐assembly of polystyrene–poly(vinylpyridine) diblock copolymers adsorbed from a selective solvent onto smooth substrates was used to create surfaces with regularly varying chemical composition. Well‐ordered arrays of localized chemical reaction sites are formed on such surfaces with sizes and intersite distances of molecular length scales. We demonstrate site‐specific complex formation with transition metal salts resulting in a nanoscopic ordered array of metal salt–polymer complexes. Selective etching of the metal‐loaded microdomains is shown. The effect of block copolymer molecular architecture on the supramolecular structure of these ‘‘chemically functionalized’’ surfaces was studied.

Two-dimensional micelle formation of polystyrene-poly(vinylpyridine) diblock copolymers on mice surfaces

We have used atomic force microscopy to study the adsorption of PolyStyrene-Poly(VinylPyridine) (PS-PVP) block copolymers from a selective solvent onto atomically smooth mica surfaces. At certain copolymer concentrations, we observe a highly regular array of spherical surface micelles covering macroscopic areas of the substrate surface. Evidence is given for a thin homogeneous layer underneath the micelles which is probably due to adsorption of free copolymer chains and brush formation prior to the formation of the micellar structures. We discuss the quality of the self-assembled structures regarding different types of defects and try to identify means for improving the long range periodicity of the structures.

Fast position measurements with scanning line optical tweezers

Scanning line optical tweezers are a powerful tool for the study of colloidal or biomolecular systems in the low-force regime. We present a fast, high-resolution particle position measurement scheme that extends the capabilities of these instruments into the realm of dynamic measurements. The technique is based on synchronous detection of forward-scattered laser light during a line scan. We demonstrate a position resolution of better than 50 nm for bandwidths of as much as 40 kHz for pairs of microspheres trapped in a flat line potential at center-to-center separations of 1.7-6 microm.

Protein-mediated DNA loop formation and breakdown in a fluctuating environment.

Living cells provide a fluctuating, out-of-equilibrium environment in which genes must coordinate cellular function. DNA looping, which is a common means of regulating transcription, is very much a stochastic process; the loops arise from the thermal motion of the DNA and other fluctuations of the cellular environment. We present single-molecule measurements of DNA loop formation and breakdown when an artificial fluctuating force, applied to mimic a fluctuating cellular environment, is imposed on the DNA. We show that loop formation is greatly enhanced in the presence of noise of only a fraction of k_{B}T, yet find that hypothetical regulatory schemes that employ mechanical tension in the DNA-as a sensitive switch to control transcription-can be surprisingly robust due to a fortuitous cancellation of noise effects.

On the role of DNA biomechanics in the regulation of gene expression

DNA is traditionally seen as a linear sequence of instructions for cellular functions that are expressed through biochemical processes. Cellular DNA, however, is also organized as a complex hierarchical structure with a mosaic of mechanical features, and a growing body of evidence is now emerging to imply that these mechanical features are connected to genetic function. Mechanical tension, for instance, which must be felt by DNA within the heavily constrained and continually fluctuating cellular environment, can affect a number of regulatory processes implicating a role for biomechanics in gene expression complementary to that of biochemical regulation. In this article, we review evidence for such mechanical pathways of genetic regulation.

Bead size effects on protein-mediated DNA looping in tethered-particle motion experiments.

Tethered particle motion (TPM) has become an important tool for single-molecule studies of biomolecules; however, concerns remain that the method may alter the dynamics of the biophysical process under study. We investigate the effect of the attached microsphere on an illustrative biological example: the formation and breakdown of protein-mediated DNA loops in the lac repressor system. By comparing data from a conventional TPM experiment with 800 nm polystyrene beads and dark-field TPM using 50 nm Au nanoparticles, we found that the lifetimes of the looped and unlooped states are only weakly modified, less than two-fold, by the presence of the large bead. This is consistent with our expectation of weak excluded-volume effects and hydrodynamic surface interactions from the cover glass and microsphere.