E. Verpoorte - Academia.edu (original) (raw)

Papers by E. Verpoorte

Research paper thumbnail of Chemical sensing using an integrated microfluidic system based on the Berthelot reaction

Sensors and Actuators B: Chemical, 2001

The Berthelot reaction is a well-established colorimetric method for the determination of ammonia... more The Berthelot reaction is a well-established colorimetric method for the determination of ammonia. It has been investigated with the particular aim of incorporating it into a simple, reliable analytical micro¯uidic sensing system. Absorbance measurements for the complex formed when this reaction is performed in micro¯uidic chips compare very well to those obtained in a spectrophotometric system. The very high reproducibility and ef®ciency of mixing by diffusion in the micro¯uidic chip make it a useful tool for future studies of other chemical methods where kinetics are a limiting factor for the response time. # (A. Daridon).

Research paper thumbnail of Indirect Electro-Osmotic Pumping for Direct Sampling from Bioreactors

Micro Total Analysis Systems 2001, 2001

Research paper thumbnail of Behaviour of Human Umbilical Vein Endothelial Cells (HUVEC) Cultivated in Microfluidic channels

2006 International Conference on Microtechnologies in Medicine and Biology, 2006

Our long-term goal is to develop advanced tools for cell studies and analysis based on microfluid... more Our long-term goal is to develop advanced tools for cell studies and analysis based on microfluidic systems. In this paper, we report on endothelial cell cultivation in microchannels and 96-well tissue plates, and compare cell phenotype and cellular status in the two environments This was done under both pro-inflammatory conditions (cell stimulation in the presence of the cytokine, Tumour Necrosis Factor, TNFalpha) and normal (medium only) conditions. In addition, we considered the behaviour of cells in a pro-inflammatory environment in the presence of an anti-inflammatory drug

Research paper thumbnail of Characterization of a microfluidic dispensing system for localised stimulation of cellular networks

Lab on a Chip, 2006

We present a 3-D microfluidic device designed for localized drug delivery to cellular networks. T... more 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.

Research paper thumbnail of Multiple flow profiles for two-phase flow in single microfluidic channels through site-selective channel coating

Lab on a Chip, 2011

An approach to control two-phase flow systems in a poly(dimethylsiloxane) (PDMS) microfluidic dev... more An approach to control two-phase flow systems in a poly(dimethylsiloxane) (PDMS) microfluidic device using spatially selective surface modification is demonstrated. Side-by-side flows of ethanol : water solutions containing different polymers are used to selectively modify both sides of a channel by laminar flow patterning. Introduction of air pockets during modification allows for control over the length of the channel section that is modified. This approach makes it possible to achieve slug flow and side-by-side flow of water : 1-octanol simultaneously within the same PDMS channel, without the need of additional structural elements. A key finding is that conditioning of the PDMS channels with 1-octanol before polymer deposition is crucial to achieving stable side-by-side flows.

Research paper thumbnail of Fabrication of multilayer systems combining microfluidic and microoptical elements for fluorescence detection

Journal of Microelectromechanical Systems, 2001

This paper presents the fabrication of a microchemical chip for the detection of fluorescence spe... more This paper presents the fabrication of a microchemical chip for the detection of fluorescence species in microfluidics. The microfluidic network is wet-etched in a Borofloat 33 (Pyrex) glass wafer and sealed by means of a second wafer. Unlike other similar chemical systems, the detection system is realized with the help of microfabrication techniques and directly deposited on both sides of the microchemical chip. The detection system is composed of the combination of refractive microlens arrays and chromium aperture arrays. The microfluidic channels are 60 m wide and 25 m deep. The utilization of elliptical microlens arrays to reduce aberration effects and the integration of an intermediate (between the two bonded wafers) aluminum aperture array are also presented. The elliptical microlenses have a major axis of 400 m and a minor axis of 350 m. The circular microlens diameters range from 280 to 300 m. The apertures deposited on the outer chip surfaces are etched in a 3000-A-thick chromium layer, whereas the intermediate aperture layer is etched in a 1000-A-thick aluminum layer. The overall thickness of this microchemical system is less than 1.6 mm. The wet-etching process and new bonding procedures are discussed. Moreover, we present the successful detection of a 10-nM Cy5 solution with a signal-to-noise ratio (SNR) of 21 dB by means of this system.

Research paper thumbnail of 481 Editorial RS Muller 482 Fabrication of Multilayer Systems Combining Microfluidic and Microoptical Elements for Fluorescence Detection

Research paper thumbnail of Microdialysis-Coupled Enzymatic Microreactor for in Vivo Glucose Monitoring in Rats

Analytical Chemistry, 2013

Continuous glucose monitoring (CGM) is an important aid for diabetic patients to optimize glycemi... more Continuous glucose monitoring (CGM) is an important aid for diabetic patients to optimize glycemic control and to prevent long-term complications. However, current CGM devices need further miniaturization and improved functional performance. We have coupled a previously described microfluidic chip with enzymatic microreactor (EMR) to a microdialysis probe and evaluated the performance of this system for monitoring subcutaneous glucose concentration in rats. Nanoliter volumes of microdialysis sample are efficiently reacted with continuously supplied glucose oxidase (GOx) solution in the EMR. The hydrogen peroxide produced is amperometrically detected at a (polypyrrole (PPy)-protected) thin-film Pt electrode. Subcutaneous glucose concentration was continuously monitored in anesthetized rats in response to intravenous injections of 20% glucose (w/v), 5 U/kg insulin, or saline as a control. In vitro evaluation showed a linear range of 2.1-20.6 mM and a sensitivity of 7.8 ± 1.0 nA/mM (n = 6). The physical lag time between microdialysis and the analytical signal was approximately 18 min. The baseline concentration of blood glucose was 10.2 ± 2.3 mM. After administering glucose to the rats, glucose levels increased by about 2 mM to 12.1 ± 2.3 mM in blood and 11.9 ± 1.5 mM in subcutaneous interstitial fluid (ISF). After insulin administration, glucose levels decreased by about 8 mM relative to baseline to 2.1 ± 0.6 mM in blood and 2.1 ± 0.9 mM in ISF. A microfluidic device with integrated chaotic mixer and EMR has been successfully combined with subcutaneous microdialysis to continuously monitor glucose in rats. This proof-of-principle demonstrates the feasibility of improved miniaturization in CGM based on microfluidics.

Research paper thumbnail of An Integrated Fritless Column for On-Chip Capillary Electrochromatography with Conventional Stationary Phases

Analytical Chemistry, 2002

A new polymer device for use with conventional particulate stationary phases for on-chip, fritles... more A new polymer device for use with conventional particulate stationary phases for on-chip, fritless, capillary electrochromatography (CEC) has been realized. The structure includes an injector and a tapered column in which the particles of the stationary phase are retained and stabilized. The chips were easily fabricated in poly(dimethylsiloxane) using deep-reactive-ion-etched silicon masters, and tested using a capillary electrophoretic separation of FITC-labeled amino acids. To perform CEC, the separation channel was packed using a vacuum with 3-microm, octadecylsilanized silica microspheres. The packing was stabilized in the column by a thermal treatment, and its stability and quality were evaluated using in-column indirect fluorescence detection. The effects of voltage on electro-osmotic flow and on efficiency were investigated, and the separation of two neutral compounds was achieved in less than 15 s.

Research paper thumbnail of Micellar Electrokinetic Chromatography Separations and Analyses of Biological Samples on a Cyclic Planar Microstructure

Analytical Chemistry, 1996

Micellar electrokinetic capillary chromatography (MECC) separations and analyses of biological sa... more Micellar electrokinetic capillary chromatography (MECC) separations and analyses of biological samples on a planar glass microchip capillary electrophoresis device with laser-induced fluorescence solute detection are discussed. A cyclic channel system which permits dead volume free repeated column switching and thus the use of various channel lengths together with a relatively low applied separation voltage is described. It features an unbiased, dead volume free electrokinetic sample inlet system of approximately 12 pL. Because of the small cross section and favorable heat dissipation in glass microstructures, MECC separations with an electric field strength of up to 2000 V/cm achieving efficiencies of submicrometer plate heights can be performed. After a separation length of 2 cm, six fluorescein isothiocyanate labeled amino acids are shown to be separable within a few seconds and with an imprecision for peak areas (or heights) and detection times of < 2% and < 0.5%, respectively. Without application of electrokinetic solute stacking, the detection limit of fluorescein isothiocyanate labeled arginine is 3.3 nM, corresponding to approximately 40 zmol injected. Furthermore, the feasibility of directly applying human urine and serum samples onto the uncoated channel system is demonstrated and first data of the successful performance of a chip-based MECC immunoassay for serum theophylline are presented. Compared to MECC in conventional fused-silica capillaries, MECC analyses on microchips can be performed 1-2 orders of magnitude faster, with higher efficiency and at no expense of accuracy and precision. Furthermore, versatility is shown to be much increased with the use of a cyclic rather than a single-path channel system. The MECC separation efficiency of fluorescein isothiocyanate labeled amino acids is shown to be comparable to that obtained by gel electrophoresis performed in the same chip layout.

Research paper thumbnail of Integrated ion sensors: how much more should be done?

IEEE 4th Technical Digest on Solid-State Sensor and Actuator Workshop, 1990

The endeavors of a number of academic labs to address the difficulties associated with ion-sensit... more The endeavors of a number of academic labs to address the difficulties associated with ion-sensitive field effect transistors (ISFETs) are examined. The focus is entirely on these devices, since most others, such as enzyme FETs, extended gate, and diode devices, are all based on the same principles. The focus is on several of the more troublesome areas associated with ISFETs

Research paper thumbnail of Chemical sensing using an integrated microfluidic system based on the Berthelot reaction

Sensors and Actuators B: Chemical, 2001

The Berthelot reaction is a well-established colorimetric method for the determination of ammonia... more The Berthelot reaction is a well-established colorimetric method for the determination of ammonia. It has been investigated with the particular aim of incorporating it into a simple, reliable analytical micro¯uidic sensing system. Absorbance measurements for the complex formed when this reaction is performed in micro¯uidic chips compare very well to those obtained in a spectrophotometric system. The very high reproducibility and ef®ciency of mixing by diffusion in the micro¯uidic chip make it a useful tool for future studies of other chemical methods where kinetics are a limiting factor for the response time. # (A. Daridon).

Research paper thumbnail of Indirect Electro-Osmotic Pumping for Direct Sampling from Bioreactors

Micro Total Analysis Systems 2001, 2001

Research paper thumbnail of Behaviour of Human Umbilical Vein Endothelial Cells (HUVEC) Cultivated in Microfluidic channels

2006 International Conference on Microtechnologies in Medicine and Biology, 2006

Our long-term goal is to develop advanced tools for cell studies and analysis based on microfluid... more Our long-term goal is to develop advanced tools for cell studies and analysis based on microfluidic systems. In this paper, we report on endothelial cell cultivation in microchannels and 96-well tissue plates, and compare cell phenotype and cellular status in the two environments This was done under both pro-inflammatory conditions (cell stimulation in the presence of the cytokine, Tumour Necrosis Factor, TNFalpha) and normal (medium only) conditions. In addition, we considered the behaviour of cells in a pro-inflammatory environment in the presence of an anti-inflammatory drug

Research paper thumbnail of Characterization of a microfluidic dispensing system for localised stimulation of cellular networks

Lab on a Chip, 2006

We present a 3-D microfluidic device designed for localized drug delivery to cellular networks. T... more 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.

Research paper thumbnail of Multiple flow profiles for two-phase flow in single microfluidic channels through site-selective channel coating

Lab on a Chip, 2011

An approach to control two-phase flow systems in a poly(dimethylsiloxane) (PDMS) microfluidic dev... more An approach to control two-phase flow systems in a poly(dimethylsiloxane) (PDMS) microfluidic device using spatially selective surface modification is demonstrated. Side-by-side flows of ethanol : water solutions containing different polymers are used to selectively modify both sides of a channel by laminar flow patterning. Introduction of air pockets during modification allows for control over the length of the channel section that is modified. This approach makes it possible to achieve slug flow and side-by-side flow of water : 1-octanol simultaneously within the same PDMS channel, without the need of additional structural elements. A key finding is that conditioning of the PDMS channels with 1-octanol before polymer deposition is crucial to achieving stable side-by-side flows.

Research paper thumbnail of Fabrication of multilayer systems combining microfluidic and microoptical elements for fluorescence detection

Journal of Microelectromechanical Systems, 2001

This paper presents the fabrication of a microchemical chip for the detection of fluorescence spe... more This paper presents the fabrication of a microchemical chip for the detection of fluorescence species in microfluidics. The microfluidic network is wet-etched in a Borofloat 33 (Pyrex) glass wafer and sealed by means of a second wafer. Unlike other similar chemical systems, the detection system is realized with the help of microfabrication techniques and directly deposited on both sides of the microchemical chip. The detection system is composed of the combination of refractive microlens arrays and chromium aperture arrays. The microfluidic channels are 60 m wide and 25 m deep. The utilization of elliptical microlens arrays to reduce aberration effects and the integration of an intermediate (between the two bonded wafers) aluminum aperture array are also presented. The elliptical microlenses have a major axis of 400 m and a minor axis of 350 m. The circular microlens diameters range from 280 to 300 m. The apertures deposited on the outer chip surfaces are etched in a 3000-A-thick chromium layer, whereas the intermediate aperture layer is etched in a 1000-A-thick aluminum layer. The overall thickness of this microchemical system is less than 1.6 mm. The wet-etching process and new bonding procedures are discussed. Moreover, we present the successful detection of a 10-nM Cy5 solution with a signal-to-noise ratio (SNR) of 21 dB by means of this system.

Research paper thumbnail of 481 Editorial RS Muller 482 Fabrication of Multilayer Systems Combining Microfluidic and Microoptical Elements for Fluorescence Detection

Research paper thumbnail of Microdialysis-Coupled Enzymatic Microreactor for in Vivo Glucose Monitoring in Rats

Analytical Chemistry, 2013

Continuous glucose monitoring (CGM) is an important aid for diabetic patients to optimize glycemi... more Continuous glucose monitoring (CGM) is an important aid for diabetic patients to optimize glycemic control and to prevent long-term complications. However, current CGM devices need further miniaturization and improved functional performance. We have coupled a previously described microfluidic chip with enzymatic microreactor (EMR) to a microdialysis probe and evaluated the performance of this system for monitoring subcutaneous glucose concentration in rats. Nanoliter volumes of microdialysis sample are efficiently reacted with continuously supplied glucose oxidase (GOx) solution in the EMR. The hydrogen peroxide produced is amperometrically detected at a (polypyrrole (PPy)-protected) thin-film Pt electrode. Subcutaneous glucose concentration was continuously monitored in anesthetized rats in response to intravenous injections of 20% glucose (w/v), 5 U/kg insulin, or saline as a control. In vitro evaluation showed a linear range of 2.1-20.6 mM and a sensitivity of 7.8 ± 1.0 nA/mM (n = 6). The physical lag time between microdialysis and the analytical signal was approximately 18 min. The baseline concentration of blood glucose was 10.2 ± 2.3 mM. After administering glucose to the rats, glucose levels increased by about 2 mM to 12.1 ± 2.3 mM in blood and 11.9 ± 1.5 mM in subcutaneous interstitial fluid (ISF). After insulin administration, glucose levels decreased by about 8 mM relative to baseline to 2.1 ± 0.6 mM in blood and 2.1 ± 0.9 mM in ISF. A microfluidic device with integrated chaotic mixer and EMR has been successfully combined with subcutaneous microdialysis to continuously monitor glucose in rats. This proof-of-principle demonstrates the feasibility of improved miniaturization in CGM based on microfluidics.

Research paper thumbnail of An Integrated Fritless Column for On-Chip Capillary Electrochromatography with Conventional Stationary Phases

Analytical Chemistry, 2002

A new polymer device for use with conventional particulate stationary phases for on-chip, fritles... more A new polymer device for use with conventional particulate stationary phases for on-chip, fritless, capillary electrochromatography (CEC) has been realized. The structure includes an injector and a tapered column in which the particles of the stationary phase are retained and stabilized. The chips were easily fabricated in poly(dimethylsiloxane) using deep-reactive-ion-etched silicon masters, and tested using a capillary electrophoretic separation of FITC-labeled amino acids. To perform CEC, the separation channel was packed using a vacuum with 3-microm, octadecylsilanized silica microspheres. The packing was stabilized in the column by a thermal treatment, and its stability and quality were evaluated using in-column indirect fluorescence detection. The effects of voltage on electro-osmotic flow and on efficiency were investigated, and the separation of two neutral compounds was achieved in less than 15 s.

Research paper thumbnail of Micellar Electrokinetic Chromatography Separations and Analyses of Biological Samples on a Cyclic Planar Microstructure

Analytical Chemistry, 1996

Micellar electrokinetic capillary chromatography (MECC) separations and analyses of biological sa... more Micellar electrokinetic capillary chromatography (MECC) separations and analyses of biological samples on a planar glass microchip capillary electrophoresis device with laser-induced fluorescence solute detection are discussed. A cyclic channel system which permits dead volume free repeated column switching and thus the use of various channel lengths together with a relatively low applied separation voltage is described. It features an unbiased, dead volume free electrokinetic sample inlet system of approximately 12 pL. Because of the small cross section and favorable heat dissipation in glass microstructures, MECC separations with an electric field strength of up to 2000 V/cm achieving efficiencies of submicrometer plate heights can be performed. After a separation length of 2 cm, six fluorescein isothiocyanate labeled amino acids are shown to be separable within a few seconds and with an imprecision for peak areas (or heights) and detection times of < 2% and < 0.5%, respectively. Without application of electrokinetic solute stacking, the detection limit of fluorescein isothiocyanate labeled arginine is 3.3 nM, corresponding to approximately 40 zmol injected. Furthermore, the feasibility of directly applying human urine and serum samples onto the uncoated channel system is demonstrated and first data of the successful performance of a chip-based MECC immunoassay for serum theophylline are presented. Compared to MECC in conventional fused-silica capillaries, MECC analyses on microchips can be performed 1-2 orders of magnitude faster, with higher efficiency and at no expense of accuracy and precision. Furthermore, versatility is shown to be much increased with the use of a cyclic rather than a single-path channel system. The MECC separation efficiency of fluorescein isothiocyanate labeled amino acids is shown to be comparable to that obtained by gel electrophoresis performed in the same chip layout.

Research paper thumbnail of Integrated ion sensors: how much more should be done?

IEEE 4th Technical Digest on Solid-State Sensor and Actuator Workshop, 1990

The endeavors of a number of academic labs to address the difficulties associated with ion-sensit... more The endeavors of a number of academic labs to address the difficulties associated with ion-sensitive field effect transistors (ISFETs) are examined. The focus is entirely on these devices, since most others, such as enzyme FETs, extended gate, and diode devices, are all based on the same principles. The focus is on several of the more troublesome areas associated with ISFETs