Experimental investigation of the flow induced by artificial cilia.

The fluid transport produced by rectangular shaped, magnetically actuated artificial cilia of 70 µm length and 20 µm width was determined by means of phase-locked Micro Particle Image Velocimetry (µPIV) measurements in a closed microfluidic chamber. The phase-averaged flow produced by the artificial cilia reached up to 130 µm s(-1) with an actuation cycle frequency of 10 Hz. Analysis of the measured flow data indicate that the present system is capable of achieving volume flow rates of V[combining dot above](cilia) = 14 ± 4 µl min(-1) in a micro channel of 0.5 × 5 mm(2) cross-sectional area when no back pressure is built up. This corresponds to an effective pressure gradient of 6 ± 1 Pa m(-1), which equals a pressure difference of 0.6 ± 0.1 mPa over a distance of 100 µm between two rows of cilia. These results were derived analytically from the measured velocity profile by treating the cilia as a thin boundary layer. While the cilia produce phase-averaged velocities of the order of O(10(2)µm s(-1)), time-resolved measurements showed that the flow field reverses two times during one actuation cycle inducing instantaneous velocities of up to approximately 2 mm s(-1). This shows that the flow field is dominated by fluid oscillations and flow rates are expected to increase if the beating motion of the cilia is further improved.

Magnetically-actuated artificial cilia for microfluidic propulsion.

In this paper we quantitatively analyse the performance of magnetically-driven artificial cilia for lab-on-a-chip applications. The artificial cilia are fabricated using thin polymer films with embedded magnetic nano-particles and their deformation is studied under different external magnetic fields and flows. A coupled magneto-mechanical solid-fluid model that accurately captures the interaction between the magnetic field, cilia and fluid is used to simulate the cilia motion. The elastic and magnetic properties of the cilia are obtained by fitting the results of the computational model to the experimental data. The performance of the artificial cilia with a non-uniform cross-section is characterised using the numerical model for two channel configurations that are of practical importance: an open-loop and a closed-loop channel. We predict that the flow and pressure head generated by the artificial cilia can be as high as 18 microlitres per minute and 3 mm of water, respectively. We also study the effect of metachronal waves on the flow generated and show that the fluid propelled increases drastically compared to synchronously beating cilia, and is unidirectional. This increase is significant even when the phase difference between adjacent cilia is small. The obtained results provide guidelines for the optimal design of magnetically-driven artificial cilia for microfluidic propulsion.

Surface-attached PDMAA-GRGDSP hybrid polymer monolayers that promote the adhesion of living cells.

Peptide-polymer hybrid molecules are being introduced, where one part of the molecule (i.e., the peptide) promotes the adhesion of living cells, whereas the other part of the molecule (i.e., the synthetic polymer) is known to prevent cell adhesion. The hybrid copolymer, poly(dimethylacrylamide) (PDMAA)-glycine-arginine-glycine-aspartic acid-serine-proline (GRGDSP) was synthesized by first preparing an initiator-modified peptide and in a second step growing the PDMAA block directly off the peptide through atom transfer radical polymerization (ATRP). The PDMAA block length can be varied by adjusting appropriate polymerization conditions, thereby changing progressively the amount of the cell-repelling part of the molecule. The hybrid copolymer was further used to prepare surface-attached peptide-polymer monolayers at planar solid glass substrates through a photochemical immobilization process. By blending of the hybrid copolymer with PDMAA homopolymer (i.e., without peptide), the apparent peptide film concentration can be varied in a very simple manner. The adhesion of human skin fibroblast cells in serum-free medium was investigated as a function of the amount of peptide-polymer in the solution used for film preparation. Cells do not adhere to a pure PDMAA monolayer; however, already 0.02 wt % of peptide in the film is enough to induce cell adhesion, and 0.1 wt % promotes stress-fiber formation within adherent cells. Using lithographical means, chemically micropatterned peptide-polymer films were prepared that allow for a spatial control of the adhesion of living cells and thus they constitute a simple platform for the design of live-cell biochips.

Single-step centrifugal hematocrit determination on a 10-$ processing device.

We present a novel concept to process human blood on a spinning polymer disk for the determination of the hematocrit level by simple visual inspection. The microfluidic disk which is spun by a macroscopic drive unit features an upstream metering structure and a downstream blind channel where the centrifugally enforced sedimentation of the blood is performed. The bubble-free priming of the blind channel is governed by centrifugally assisted capillary filling along the sloped hydrophilic side-wall and the lid as well as the special shape of the dead end of the two-layer channel. The hematocrit is indicated at the sharp phase boundary between the plasma and the segregated cellular pellet on a disk-imprinted calibrated scale. This way, we conduct the hematocrit determination of human blood within 5 min at a high degree of linearity (R(2) = 0.999) and at a high accuracy (CV = 4.7%) spanning over the physiological to pathological working range. As all processing steps including the priming, the metering to a defined volume as well as the centrifugation are executed automatically during rotation, the concept is successfully demonstrated in a conventional PC-CDROM drive while delivering the same performance (R(2) = 0.999, CV = 4.3%).

The polymer-supported phospholipid bilayer: tethering as a new approach to substrate-membrane stabilization.

We present a new molecular engineering approach in which a polymer-supported phospholipid bilayer is vertically stabilized by controlled covalent tethering at both the polymer-substrate and polymer-bilayer interfaces. This approach is based on lipopolymer molecules, which not only form a polymer cushion between the phospholipid bilayer and a solid glass substrate but also act as covalent connections (tethers) between the bilayer and cushion. Our approach involves Langmuir-Blodgett transfer of a phospholipid-lipopolymer monolayer followed by Schaefer transfer of a pure phospholipid monolayer and is capable of varying the tethering density between the polymer layer and the phospholipid bilayer in a very controlled manner. Further stabilization is achieved if the glass substrate is surface-functionalized with a benzophenone silane. In this case, a photocross-linking reaction between the polymer and benzophenone group allows for the covalent attachment of the polymer cushion to the glass substrate. This approach is similar to that recently reported by Wagner and Tamm in which double tethering is achieved via lipopolymer silanes (Wagner, M. L.; Tamm, L. K. Biophys. J. 2000, 79, 1400). To obtain a deeper understanding of how the covalent tethering affects the lateral mobility of the bilayer, we performed fluorescence recovery after photobleaching (FRAP) experiments on polymer-tethered bilayers at different tethering densities (lipopolymer/phospholipid molar ratios). The FRAP data clearly indicate that the hydrophobic lipopolymer moieties act as rather immobile obstacles within the phospholipid bilayer, thereby leading to hindered diffusion of phospholipids. Whereas the high lateral diffusion coefficient of D = 17.7 mum(2)/s measured at low tethering density (5 mol % lipopolymer) indicates rather unrestricted motion within the bilayer, corresponding values at moderate (10 mol % lipopolymer) and high (30 mol % lipopolymer) tethering densities of D = 9.7 mum(2)/s and D = 1.1 mum(2)/s, respectively, show significant hindered diffusion. These results are contrary to the recent findings on similar membrane systems reported by Wagner and Tamm in which no significant change in phospholipid diffusion was found between 0 and 10 mol % lipopolymer. Our experimental report leads to a deeper understanding of the complex problem of interlayer coupling and offers a path toward a compromise between stability of the whole system and lateral mobility within the bilayer. Furthermore, the FRAP measurements show that polymer-tethered membranes are very interesting model systems for studying problems of restricted diffusion within two-dimensional fluids.

Surface attached ultrathin polymer monolayers for control of cell adhesion.

BACKGROUND: Calcific degeneration is the major drawback of bioprostheses. None of the numerous preventive approaches omitted calcification. Previous studies showed that cellular surface seeding decreases calcium uptake in vitro but achievement of coverage remains problematic. A new approach is presented masking glutaraldehyde residues with a polymer layer allowing cell seeding. The aim of this study was to evaluate different polymers for suitability. METHODS: Ten polymers--covalently bound to glass--were tested for their ability to seed animal and human cells. Quality of coverage was evaluated by light and scanning electron microscopy, and polymers were characterized physicochemically. RESULTS: Quality of cellular growth was similar for canine and human cells. Five polymers allowed excellent surface coverage, two led to a decrease of cell adherence, and four to poor cellular growth. No correlation between molecular weight, thickness, hydrophilicity, or charge of the polymer and cell growth was found. CONCLUSIONS: Polymer monolayers can promote cellular growth but without correlation to physicochemical characteristics. Polymers covalently bound to biologic tissue appear to be a promising approach for achieving cellular coverage of biomaterials.