Biomedical subjects

Sander Koster

Publications and source records attributed to Sander Koster.

8 recordsLinked to original sources

PubMed2006

Characterization of a microfluidic dispensing system for localised stimulation of cellular networks.

We present a 3-D microfluidic device designed for localized drug delivery to cellular networks. The device features a flow cell comprising a main channel for nutrient delivery as well as multiple channels for drug delivery. This device is one key component of a larger, fully integrated system now under development, based upon a microelectrode array (MEA) with on-chip CMOS circuitry for recording and stimulation of electrogenic cells (e.g. neurons, cardiomyocytes). As a critical system unit, the microfluidics must be carefully designed and characterized to ensure that candidate drugs are delivered to specific regions of the culture at known concentrations. Furthermore, microfluidic design and functionality is dictated by the size, geometry, and material/electrical characteristics of the CMOS MEA. Therefore, this paper reports on the design considerations and fabrication of the flow cell, including theoretical and experimental analysis of the mass transfer properties of the nutrient and drug flows, which are in good agreement with one another. To demonstrate proof of concept, the flow cell was mounted on a dummy CMOS chip, which had been plated with HL-1 cardiomyocytes. A test chemical compound was delivered to the cell culture in a spatially resolved manner. Envisioned applications of this stand-alone system include simultaneous toxicological testing of multiple compounds and chemical stimulation of natural neural networks for neuroscience investigations.

Algorithms↗

PubMed2006

Microfluidics/CMOS orthogonal capabilities for cell biology.

The study of individual cells and cellular networks can greatly benefit from the capabilities of microfabricated devices for the stimulation and the recording of electrical cellular events. In this contribution, we describe the development of a device, which combines capabilities for both electrical and pharmacological cell stimulation, and the subsequent recording of electrical cellular activity. The device combines the unique advantages of integrated circuitry (CMOS technology) for signal processing and microfluidics for drug delivery. Both techniques are ideally suited to study electrogenic mammalian cells, because feature sizes are of the same order as the cell diameter, approximately 50 microm. Despite these attractive features, we observe a size mismatch between microfluidic devices, with bulky fluidic connections to the outside world, and highly miniaturized CMOS chips. To overcome this problem, we developed a microfluidic flow cell that accommodates a small CMOS chip. We simulated the performances of a flow cell based on a 3-D microfluidic system, and then fabricated the device to experimentally verify the nutrient delivery and localized drug delivery performance. The flow-cell has a constant nutrient flow, and six drug inlets that can individually deliver a drug to the cells. The experimental analysis of the nutrient and drug flow mass transfer properties in the flowcell are in good agreement with our simulations. For an experimental proof-of-principle, we successfully delivered, in a spatially resolved manner, a 'drug' to a culture of HL-1 cardiac myocytes.

Cell Culture Techniques↗

PubMed2005

A high current density DC magnetohydrodynamic (MHD) micropump.

This paper describes the working principle of a DC magnetohydrodynamic (MHD) micropump that can be operated at high DC current densities (J) in 75-microm-deep microfluidic channels without introducing gas bubbles into the pumping channel. The main design feature for current generation is a micromachined frit-like structure that connects the pumping channel to side reservoirs, where platinum electrodes are located. Current densities up to 4000 A m(-2) could be obtained without noticeable Joule heating in the system. The pump performance was studied as a function of current density and magnetic field intensity, as well as buffer ionic strength and pH. Bead velocities of up to 1 mm s(-1) (0.5 microL min(-1)) were observed in buffered solutions using a 0.4 T NdFeB permanent magnet, at an applied current density of 4000 A m(-2). This pump is intended for transport of electrolyte solutions having a relatively high ionic strength (0.5-1 M) in a DC magnetic field environment. The application of this pump for the study of biological samples in a miniaturized total analysis system (microTAS) with integrated NMR detection is foreseen. In the 7 T NMR environment, a minimum 16-fold increase in volumetric flow rate for a given applied current density is expected.

Electrochemistry↗

PubMed2003

Using matrix peaks to map topography: increased mass resolution and enhanced sensitivity in chemical imaging.

It is well known in secondary ion mass spectrometry (SIMS) that sample topography leads to decreased mass resolution. Specifically, the ion's time of flight is dependent on where it was generated. Here, using matrix-enhanced SIMS, it is demonstrated that, in addition to increasing the yield of intact pseudomolecular ions, the matrix allows the user to semiquantitatively record the topography of a sample. Through mapping the topography-related mass shifts of the matrix (which leads to decreased mass resolution), the analogous mass shifts of higher mass ions can be deconvoluted and higher resolution and greater sensitivity obtained. Furthermore, the semiquantitative topographical map obtained can be compared with any chemical images obtained, allowing the user to quickly ascertain whether local intensity maximums are due to topological features or represent genuine features of interest.

Journal Article↗

PubMed2003

Electrokinetic characterization of poly(dimethylsiloxane) microchannels.

This paper characterizes the basic electrokinetic phenomena occurring within native poly(dimethylsiloxane) (PDMS) microchannels. Using simple buffers and current measurements, current density and electroosmosis data were determined in trapezoidal, reversibly sealed PDMS/PDMS and hybrid PDMS/glass channels with a cross-sectional area of 1035.5 microm(2) and about 6 cm length. This data was then compared to that obtained in an air-thermostated 50 microm inner diameter (1963.5 microm(2) cross-sectional area) fused-silica (FS) capillary of 70 cm length. Having a pH 7.8 buffer with an ionic strength (I) of 90 mM, Ohms's law was observed in the microchannels with electric field strengths of up to about 420 V/cm, which is about twice as high as for the FS capillary. The electroosmotic mobility (micro(EO)) in PDMS and FS is shown to exhibit the same general dependences on I and pH. For all configurations tested, the experimentally determined micro(EO) values were found to correlate well with the relationship micro(EO) = a + b log(I), where a and b are coefficients that are determined via nonlinear regression analysis. Electroosmotic fluid pumping in native PDMS also follows a pH dependence that can be estimated with a model based upon the ionization of silanol. Compared to FS, however, the magnitude of the electroosmotic flow in native PDMS is 50-70% smaller over the entire pH range and is difficult to maintain at acidic pH values. Thus, the origin of the negative charge at the inner wall of PDMS, glass, and FS appears to be similar but the density is lower for PDMS than for glass and FS.

Dimethylpolysiloxanes↗

PubMed2003

Electron capture and collisionally activated dissociation mass spectrometry of doubly charged hyperbranched polyesteramides.

Electron capture dissociation (ECD) of doubly protonated hyperbranched polyesteramide oligomers (1100-1900 Da) was examined and compared with the structural information obtained by low energy collisionally activated dissociation (CAD). Both the ester and amide bonds of the protonated species were cleaved easily upon ECD with the formation of odd electron (OE(.+)) or even electron (EE(+)) fragment ions. Several mechanistic schemes are proposed that describe the complex ECD fragmentation behavior of the multiply charged oligomers. In contrast to studies of biomolecules, the present results indicate that consecutive cleavages induced by intramolecular H-shifts are significant for ECD and of less importance for low energy CAD. The capture of an electron by the ionized species results in fragmentation associated with a redistribution of the excess internal energy over the products and the subsequent bond cleavage. Low energy, multiple collision CAD is found to be a more selective dissociation method than ECD in view of the observation that only amide bonds are cleaved for most of the hyperbranched polymers examined with CAD in this study. ECD appears not to provide complementary structural information compared to CAD in the study of hyperbranched polymers, even though a significantly more complex ECD fragmentation behavior is observed. ECD is shown to be of use for the structural characterization of large oligomers that may not dissociate upon low energy CAD. This is a direct result of the fact that ECD produces ionized hyperbranched oligomers with a relatively high internal energy.

Journal Article↗

PubMed2002

Isomer separation of hyperbranched polyesteramides with gas-phase H/D exchange and a novel MS(n) approach: DoDIP.

Two approaches are introduced that provide information about the isomeric composition of hyperbranched polyesteramides. The first approach is based on a novel tandem mass spectrometric (MS(n)) approach that allows the study of different types of isomeric structures by a separation based on their difference in appearance energy. The method is called DoDIP: dissociation of depleted ion populations. A first MS/MS step is used to fragment isomers with relatively low appearance energy. The isomers with higher appearance energy are fragmented in a second MS/MS step of higher energy. The second approach is based on gas-phase H/D exchange experiments that result in a bimodal isotopic distribution for oligomers X(n)D(n+1) of which one distribution corresponds to a type of isomeric structure that exhibits H/D exchange behaviour and the other to an isomeric structure that does not exhibit H/D exchange behaviour. X is a difunctional anhydride of phthalic acid (P), 1,2-cyclohexanedicarboxylic acid (C), succinic acid (S) or glutaric acid (G). D in X(n)D(n+1) is a trifunctional diisopropanolamine and n the degree of polymerization. The type of isomeric structure that does not exhibit H/D exchange behaviour has a non-alternating monomer sequence that contains an amine bond with a relatively high proton affinity. The other isomeric structure that does exhibit H/D exchange behaviour has an alternating monomer sequence containing only amide and ester bonds with relatively low proton affinity. Oligomer structures were confirmed with additional MS(2) experiments after H/D exchange. H/D exchange experiments on the fragments obtained after MS(2) of the parent ion show that next to previously postulated mechanisms for the cleavage of the ester and amide bond another reaction pathway must be operational. A new mechanism is introduced to explain the H/D exchange behaviour of the fragments that requires a cleavage of the amide bonds only. Two types of fragments are formed by this mechanism. One type is protonated due to the cleavage of the amide bond whereas the other type has an oxazolonium ion structure due to the loss of an additional H(2)O.

Journal Article↗

PubMedDate not supplied

The quenching of electrochemiluminescence upon oligonucleotide hybridization.

Many genomic assays rely on a distance-dependent interaction between luminescent labels, such as luminescence quenching or resonance energy transfer. We studied the interaction between electrochemically excited Ru(bpy)(3) (2+) and Cy5 in a hybridization assay on a chip. The 3' end of an oligonucleotide was labelled with Ru(bpy)(3) (2+) and the 5' end of a complementary strand with Cy5. Upon the hybridization, the electrochemiluminescence (ECL) of Ru(bpy)(3) (2+) was efficiently quenched by Cy5 with a sensitivity down to 30 nmol/L of the Cy5-labelled complementary strand. The quenching efficiency is calculated to be 78%. A similar phenomenon was observed in a comparative study using laser-excitation of Ru(bpy)(3) (2+). The hybridization with the non-labelled complementary or labelled non-complementary strand did not change the intensity of the ECL signal. Resonance energy transfer, electron transfer and static quenching mechanisms are discussed. Our results suggest that static quenching and/or electron transfer are the most likely quenching mechanisms.

Carbocyanines↗