Papers by Bart van Grinsven
physica status solidi (a), 2016
Derivation of the heat-transfer resistance R th from temperature-and power data
ACS Applied Materials & Interfaces, 2015
Aptamers are an emerging class of molecules which, due to the development of the systematic evolu... more Aptamers are an emerging class of molecules which, due to the development of the systematic evolution of ligands by exponential enrichment (SELEX) process, can recognize virtually every target ranging from ions, to proteins, and even whole cells. While there are many techniques capable of detecting template molecules with aptamer-based systems with high specificity and selectivity, they lack the possibility of integrating them into a compact and portable biosensor setup. Therefore, we will present the heat-transfer method (HTM) as an interesting alternative since this offers detection in a fast and low-cost manner and has the possibility of performing experiments with a fully integrated device. This concept has been demonstrated for a variety of applications including DNA mutation analysis and screening of cancer cells. To our knowledge, this is the first report on HTM-based detection of proteins, in this case specifically with aptamer-type receptors. For proof-of-principle purposes, measurements will be performed with the peanut allergen Ara h 1 and results indicate detection limits in the lower nanomolar regime in buffer liquid. As a first proof-ofapplication, spiked Ara h 1 solutions will be studied in a food matrix of dissolved peanut butter. Reference experiments with the quartz-crystal microbalance will allow for an estimate of the areal density of aptamer molecules on the sensor-chip surface.
Langmuir, 2015
Previous work has indicated that surface imprinted polymers (SIPs) allow for highly specific cell... more Previous work has indicated that surface imprinted polymers (SIPs) allow for highly specific cell detection through macromolecular cell imprints. The combination of SIPs with a heattransfer-based read-out technique has led to the development of a selective, label-free, low-cost, and user-friendly cell detection assay. In this study, the breast cancer cell line ZR-75-1 is used to assess the potential of the platform for monitoring the quality of a cell culture in time. For this purpose, we show that the proposed methodology is able to discriminate between the original cell line (adherent growth, ZR-75-1a) and a descendant cell line (suspension growth, ZR-75-1s). Moreover, ZR-75-1a cells were cultured for a prolonged period of time and analyzed using the heat-transfer method (HTM) at regular time intervals. The results of these experiments demonstrate that the thermal resistance (R th ) signal decays after a certain number of cell culture passages. This can likely be attributed to a compromised quality of the cell culture due to cross-contamination with the ZR-75-1s cell line, a finding that was confirmed by classical STR DNA profiling. The cells do not express the same functional groups on their membrane, resulting in a weaker bond between cell and imprint, enabling cell removal by mechanical friction, provided by flushing the measuring chamber with buffer solution. These findings were further confirmed by HTM and illustrate that the biomimetic sensor platform can be used as an assay for monitoring the quality of cell cultures in time.
2014 IEEE 27th International Conference on Micro Electro Mechanical Systems (MEMS), 2014
In this paper the successful integration of heat-transfer resistance measurements with a digital ... more In this paper the successful integration of heat-transfer resistance measurements with a digital microfluidic chip is shown. The integrated miniaturized platform allows the automated label-free detection of biomolecular interactions. To immobilize biomolecules on the hydrophobic chip surface, hydrophilic gold sensing patches are created by means of a recently described dry lift-off technique that leaves the chip surface unaffected. DNA melting analysis was performed for validating the integrated device.
Sensors and Actuators B: Chemical, 2014
Graphene oxide (GO), with its small dimension and high surface-to-volume ratio, can enhance the b... more Graphene oxide (GO), with its small dimension and high surface-to-volume ratio, can enhance the binding capacity and sensitivity of molecularly imprinted polymers (MIPs). Therefore, a straightforward and fast method was developed to graft MIPs onto GO by reversible addition-fragmentation chain transfer (RAFT) polymerization. First, the initiator was linked to the GO in a simple two-step process which was verified via UV-vis spectroscopy. Subsequently, a MIP layer for histamine was grown onto the functionalized surface by RAFT crosslinking polymerization, enabling control over the imprint structure. The formation of a hybrid GO-MIP structure, particles surrounded with a polymer network of ∼2.4 nm thick, was verified by atomic force microscopy (AFM). Classical batch rebinding experiments demonstrated the specificity of the MIP towards its original template histamine. Next, the heat-transfer method (HTM) was applied, a novel sensing technique requiring only two thermocouples and an adjustable heat source. This method has been employed for the detection of small organic molecules with bulk MIPs, but never with a GO-hybrid structure. For proof-of-principle purposes, silicon substrates were functionalized with the GO-MIPs and sensing was performed on histamine in buffer solutions. The designed sensor platform could detect histamine in the nanomolar regime, similar to conventional techniques. In summary, we have developed a fast and straightforward method to prepare MIP-GO hybrids which were able to measure histamine in buffer solutions by thermal detection. Since GO exhibits excellent thermal properties, this opens the window to sensing of small organic molecules in relevant biological samples. .be (M. Peeters).
physica status solidi (a), 2015
Phone: þ32 (011) 26 88 93, Fax: þ32 (011) 26 88 99 † K. Eersels and B. van Grinsven contributed e... more Phone: þ32 (011) 26 88 93, Fax: þ32 (011) 26 88 99 † K. Eersels and B. van Grinsven contributed equally to this work.
physica status solidi (a), 2013
ACS Applied Materials & Interfaces, 2014
In recent years, biosensors have become increasingly important in various scientific domains incl... more In recent years, biosensors have become increasingly important in various scientific domains including medicine, biology, and pharmacology, resulting in an increased demand for fast and effective readout techniques. In this Spotlight on Applications, we report on the recently developed heat-transfer method (HTM) and illustrate the use of the technique by zooming in on four established bio(mimetic) sensor applications: (i) mutation analysis in DNA sequences, (ii) cancer cell identification through surface-imprinted polymers, (iii) detection of neurotransmitters with molecularly imprinted polymers, and (iv) phase-transition analysis in lipid vesicle layers. The methodology is based on changes in heat-transfer resistance at a functionalized solid−liquid interface. To this extent, the device applies a temperature gradient over this interface and monitors the temperature underneath and above the functionalized chip in time. The heat-transfer resistance can be obtained by dividing this temperature gradient by the power needed to achieve a programmed temperature. The low-cost, fast, label-free and userfriendly nature of the technology in combination with a high degree of specificity, selectivity, and sensitivity makes HTM a promising sensor technology.
Physica Status Solidi a-Applications and Materials Science, 2014
Phone: þ32 11 26 88 72, Fax þ32 11 26 88 99 y These authors contributed equally.
Sensors, 2014
In this work we present the first steps towards a molecularly imprinted polymer (MIP)-based biomi... more In this work we present the first steps towards a molecularly imprinted polymer (MIP)-based biomimetic sensor array for the detection of small organic molecules via the heat-transfer method (HTM). HTM relies on the change in thermal resistance upon binding of the target molecule to the MIP-type receptor. A flow-through sensor cell was developed, which is segmented into four quadrants with a volume of 2.5 μL each, allowing four measurements to be done simultaneously on a single substrate. Verification measurements were conducted, in which all quadrants received a uniform treatment and all four channels exhibited a similar response. Subsequently, measurements were performed in quadrants, which were functionalized with different MIP particles. Each of these quadrants was exposed to the same buffer solution, spiked with different molecules, according to the MIP under analysis. With the flow cell design we could discriminate between similar small
Advances in Condensed Matter Physics, 2015
The phase transitions of binary lipid mixtures are studied by a combination of Peltier-element-ba... more The phase transitions of binary lipid mixtures are studied by a combination of Peltier-element-based adiabatic scanning calorimetry (pASC) and quartz crystal microbalance with dissipation monitoring (QCM-D). pASC, a novel type of calorimeter, provides valuable and unambiguous information on the heat capacity and the enthalpy, whereas QCM-D is proposed as a genuine way of determining phase diagrams by analysing the temperature dependence of the viscosity. Two binary mixtures of phospholipids with the same polar head and differing in the alkyl chain length, DMPC + DPPC and DMPC + DSPC, are discussed. Both techniques give consistent phase diagrams, which compare well with literature results, showing their capability to map the phase behaviour of pure lipids as well as lipid mixtures. This work can be considered as a departure point for further investigations on more complex lipid mixtures displaying relevant phases such as the liquid-ordered phase and solid-lipid interfaces with biologically functional importance.
MRS Proceedings, 2011
In search for a better way to monitor the hybridization and denaturation of DNA onto a diamond ba... more In search for a better way to monitor the hybridization and denaturation of DNA onto a diamond based sensor, precise knowledge about the conditions of the immediate surroundings is very critical. One of the factors that have a great influence on the stability of the measurements is the temperature of the liquid environment in which these measurements take place. With this as a focal point, the design of a precise temperature regulator based on a boron doped diamond thin film is a key factor to achieve accurate measurements on a standalone basis. In this work temperature control is achieved making use of a thin boron doped nanocrystalline diamond (B-NCD) film, which, in combination with a proportional-integral-derivative-control (PID), is able to maintain a stable temperature with an accuracy better than 0.1 8C. By letting the B-NCD-layer act as a resistor together with the appropriate control it is possible to maintain a stable temperature in a range going from room temperature till 70 8C, with an accuracy exceeding a temperature variation 0.1 8C. The first prototype makes use of a reference temperature sensor, to verify the accuracy of the results.
physica status solidi (a), 2013
Probe DNA, consisting of a 36-mer fragment was covalently immobilized on nanocrystalline chemical... more Probe DNA, consisting of a 36-mer fragment was covalently immobilized on nanocrystalline chemical vapour deposition (CVD) diamond electrodes and hybridized with a 29-mer target DNA. In this paper, we report on the label-free real-time electronic monitoring of DNA denaturation upon exposure to NaOH at different flow rates and molarities, using electrochemical impedance spectroscopy as readout technology. The impedance response was separated into a denaturation time constant and a medium exchange time constant by means of a double exponential fit. It was observed that the denaturation time is dependent on the flow rate as well as on the molarity of the NaOH. Surprisingly, it was observed that at low molarities (0.05 M) the DNA does not fully denature at low flow rates. Only after flushing the flow cell a second time with 0.05 M NaOH, complete denaturation was achieved. Confocal images were obtained and plotted in 3D graphs to confirm the results. This paper provides a systematic overview of measured denaturation times for different flow rates and at different molarities of NaOH. Optimization of these parameters can be a valuable asset in the field of mutation analysis.
International Journal of Nanomedicine, 2014
Journal of Biomedical Optics, 2014
A microcavity-based deoxyribonucleic acid (DNA) optical biosensor is demonstrated for the first t... more A microcavity-based deoxyribonucleic acid (DNA) optical biosensor is demonstrated for the first time using synthetic sapphire for the optical cavity. Transmitted and elastic scattering intensity at 1510 nm are analyzed from a sapphire microsphere (radius 500 μm, refractive index 1.77) on an optical fiber half coupler. The 0.43 nm angular mode spacing of the resonances correlates well with the optical size of the sapphire sphere. Probe DNA consisting of a 36-mer fragment was covalently immobilized on a sapphire microsphere and hybridized with a 29-mer target DNA. Whispering gallery modes (WGMs) were monitored before the sapphire was functionalized with DNA and after it was functionalized with single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). The shift in WGMs from the surface modification with DNA was measured and correlated well with the estimated thickness of the add-on DNA layer. It is shown that ssDNA is more uniformly oriented on the sapphire surface than dsDNA. In addition, it is shown that functionalization of the sapphire spherical surface with DNA does not affect the quality factor (Q ≈ 10 4 ) of the sapphire microspheres. The use of sapphire is especially interesting because this material is chemically resilient, biocompatible, and widely used for medical implants.
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2007
Electrogram (EGM) delineation is an increasingly important task to be performed in implantable ca... more Electrogram (EGM) delineation is an increasingly important task to be performed in implantable cardiac devices such as pacemakers and defibrillators. Reliable detection and classification of EGM components might help to minimize the risk of false detections. Efforts are therefore undertaken to examine whether existing ECG delineators can be adapted for the delineation of EGMs. One issue to be solved is the low sampling rate at which EGMs are acquired. In this study we investigate performance degradation of an existing wavelet-based ECG delineator by a stepwise reduction of the sampling rate. It is shown that for signals sampled at 1 kHz, no significant performance degradation occurs in P or T wave delineation. The performance of QRS delineation is affected only at the lowest sampling rate of 62.5 Hz. For signals originally sampled at 250 Hz, no degradation in delineation performance is observed. It is concluded that the automatic delineation of ECGs can be performed at sampling rate...
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Papers by Bart van Grinsven