Biomedical subjects

Fredrik Nikolajeff

Publications and source records attributed to Fredrik Nikolajeff.

7 recordsLinked to original sources

PubMed2005

Bioactive heparin immobilized onto microfluidic channels in poly(dimethylsiloxane) results in hydrophilic surface properties.

A new composition of heparin coating for microfluidic systems made out of poly(dimethylsiloxane) (PDMS) was developed and evaluated. The coating that consists of a conditioning polyamine layer followed by two heparin/glutaraldehyde layers, resulted in channel surfaces with sufficient wettability to obtain flow of human normal plasma by capillary force alone. Hydrophilic channel walls are a desirable characteristic in microfluidic devices, since alternative pumping mechanisms must otherwise be included into the system. The immobilized heparin showed high antithrombin-binding capacity and a low degree of blood-material interaction. Plasma in contact with heparin-coated PDMS formed no detectable fibrin in a spectrophotometric assay by which plasma in contact with non-treated PDMS showed complete coagulation. The quartz crystal microbalance technique with energy dissipation monitoring (QCM-D) was utilized to obtain detailed information regarding adsorption kinetics and structural properties of the different layers composing the heparin coating.

Blood Flow Velocity↗

PubMed2005

Thermoplastic microfluidic platform for single-molecule detection, cell culture, and actuation.

We have developed a multipurpose microfluidic platform that allows for sensitive fluorescence detection on inexpensive disposable chips. The fabrication scheme involves rapid injection molding of thermoplastics, followed by silica deposition and covalent attachment of an unstructured flexible lid. This combines the virtues of elastomer technology with high-throughput compact disk injection molding. Using this technique, the time to produce 100 chips using a single master can be lowered from more than 1 week by standard PDMS technologies to only a couple hours. The optical properties of the fabricated chips were evaluated by studying individual fluorescence-labeled DNA molecules in a microchannel. Concatemeric DNA molecules were generated through rolling circle replication of circular DNA molecules, which were labeled by hybridization of fluorescence-tagged oligonucleotides. Rolling circle products (RCPs) were detected after as little as 5 min of DNA polymerization, and the RCPs in solution showed no tendency for aggregation. To illustrate the versatility of the platform, we demonstrate two additional applications: The flexible property of the lid was used to create a peristaltic pump generating a flow rate of 9 nL/s. Biocompatibility of the platform was illustrated by culturing Chinese hamster ovary cells for 7 days in the microfluidic channels.

Animals↗

PubMed2005

Functionality and stability of heparin immobilized onto poly(dimethylsiloxane).

Poly(dimethylsiloxane) (PDMS) has become an attractive material when working in the field of microfluidics, mainly because of the rapid prototyping process it involves. The increased surface volume ratio in microchannels makes the interaction between sample and material surface highly important, evident when handling complex biological samples such as plasma or blood. This study demonstrates a new grade of non-covalent heparin surface that adds efficient anticoagulant property to the PDMS material. The surface modification is a simple and fast one-step process performed at neutral pH, optimal when working with closed microsystems. The heparin formed a uniform and functional coating on hydrophobic PDMS with comparatively high level of antithrombin-binding capacity. In addition, long-term studies revealed that the immobilized heparin was more or less stable in the microchannels over a time of three weeks. Recalcified plasma in contact with native PDMS showed complete coagulation after 1h, while no fibrin formation was detected in plasma incubated on heparin-coated PDMS within the same time. In conclusion, we see the heparin coating developed and evaluated in this study as a tool that greatly facilitates the use of PDMS in microfluidics dealing with plasma or blood samples.

Antithrombins↗

PubMed2005

Electrokinetic-driven microfluidic system in poly(dimethylsiloxane) for mass spectrometry detection integrating sample injection, capillary electrophoresis, and electrospray emitter on-chip.

A novel microsystem device in poly(dimethylsiloxane) (PDMS) for MS detection is presented. The microchip integrates sample injection, capillary electrophoretic separation, and electrospray emitter in a single substrate, and all modules are fabricated in the PDMS bulk material. The injection and separation flow is driven electrokinetically and the total amount of external equipment needed consists of a three-channel high-voltage power supply. The instant switching between sample injection and separation is performed through a series of low-cost relays, limiting the separation field strength to a maximum of 270 V/cm. We show that this set-up is sufficient to accomplish electrospray MS analysis and, to a moderate extent, microchip separation of standard peptides. A new method of instant in-channel oxidation makes it possible to overcome the problem of irreversibly bonded PDMS channels that have recovered their hydrophobic properties over time. The fast method turns the channel surfaces hydrophilic and less prone to nonspecific analyte adsorption, yielding better separation efficiencies and higher apparent peptide mobilities.

Dimethylpolysiloxanes↗

PubMed2004

Poly(dimethylsiloxane) microchip: microchannel with integrated open electrospray tip.

A polymer microchip with an open tip for electrospray mass spectrometry is presented. The tip consists of a groove with parallel walls where a droplet can form at the end surface. A lid covers the whole chip except at the microchannel tip, which is left open. Poly(dimethylsiloxane) (PDMS) microchips were cast using a nickel mould which in turn was replicated from a dry etched silicon wafer. Tips with microchannel widths of around 50 microm could easily be replicated. Since the tip had no cover, the assembly of microchip and cover was simplified. A total ion current variation of 5% during 300 s was achieved for a 1 microM myoglobin solution. The non-complex design of the cover makes it suitable for versatile tests of chip prototypes. The nickel mould was found to be useful for PDMS microstructure fabrication. Also, such a robust mould allows casting electrospray tips in more rigid thermoset materials.

Dimethylpolysiloxanes↗

PubMed2003

Sheathless electrospray from polymer microchips.

In this study, sheathless electrospray from polymer microchips with conducting layer on the emitter tip is described for the first time. The electrospray emitter tips were fabricated directly from the end of the microchips that were made of polycarbonate or poly(methyl methacrylate) with injection molding. A variety of tip shapes and conducting coatings were evaluated using an electrospray time-of-flight mass spectrometer run in the sheathless mode. Stable electrospray was obtained both from hand-polished and machine-milled three-dimensional tips coated with either polymer-embedded gold particles or graphite particles as the conducting layer. Sputtered gold, on the other hand, suffered from poor stability mainly due to bad adhesion to the polymer tip. The durability of the different coatings was confirmed with electrochemical experiments under simulated electrospray conditions. The relative standard deviations of the response received from the ion current of the MS analysis were in the range of 3.5-12%. The detection limit for a standard mixture containing five neuropeptides was lower than 0.5 fmol. The low detection limit makes the emitter tips highly attractive for the analysis of low-abundance biological species.

Electrochemistry↗

PubMed2002

Transfer of micro-optical structures into GaAs by use of inductively coupled plasma dry etching.

The transfer of continuous-relief micro-optical structures from resist into GaAs by the use of direct-write electron-beam (e-beam) lithography followed by dry etching in an inductively coupled plasma is demonstrated. BCl3-Ar chemistry was found to give satisfactory results; N2 and Cl2 were added to change the selectivity between GaAs and e-beam resist. The transfer process generates smooth etched structures. Distortion of the diffractive structures in the transfer process was examined. Blazed gratings with a period of 10 microns were optically evaluated with a 940-nm VCSEL. This grating was a five-step approximation of a blazed profile. The diffraction efficiency was 67% in the first order, with a theoretical value of 87%. Also, simulations of the optical performance of the transferred diffractive elements were made by use of a Fourier transform of the grating profile. Our goal is to integrate micro-optical structures with VCSELs.

Journal Article↗