S. Bohm

A plastic micropump constructed with conventional techniques and materials

A plastic micropump which can be produced using conventional production techniques and materials is presented. By applying well-known techniques and materials, economic fabrication of micropumps for various applications is feasible even at low production volumes. The micropump is capable of pumping both liquid and gas at a considerable high pump rate and is self-priming, which means that it can start pumping gas in a dry state and automatically fills with liquid. Pump rates, at actuation frequencies between 2 and 500 Hz, were around 2 ml/min for water and up to 50 ml/min for air. A differential pressure of 1.25×104 Pa (125 cm water column) was reached. Basically, the micropump consists of two parts, a flat valve assembly with two passive membrane valves and an actuator placed on top. The valves were made by sandwiching a punched thin polymer film between two plastic valve parts containing the valve seats. The latter parts are made by reactive injection molding of an epoxy resin. Two types of actuators have been applied to drive the pump; an electromagnetic actuator consisting of a magnet placed in a coil and secondly a disk. The first actuator, when combined with a flexible polymer pump membrane, showed a very large pump rate for gas, up to 40 ml/min at the resonant frequency of the actuator system. A disadvantage of the electromagnetic actuator was the relatively large volume occupied by the coil giving the micropump final dimensions of 10×10×8 mm3. Application of the piezoelectric actuator reduced these dimensions down to 12×12×2 mm3 with comparable performance.

A closed-loop controlled electrochemically actuated micro-dosing system

In this paper a closed-loop controlled micromachined dosing system is presented, for the accurate manipulation of liquids in microsystems down to the nanoliter range. The applied driving force to dispense liquids originates from the electrochemical generation of gas bubbles by the electrolysis of water. The proposed dosing system comprises a micromachined channel/reservoir structure in silicon, capped with a Pyrex® cover on which a set of platinum electrodes is patterned. By adopting an interdigitated electrode geometry, the electrodes can be used for electrochemical gas generation as well as for the simultaneous determination of the total gas bubble volume, via an impedance measurement of the gas/liquid mixture in the reservoir. As this measured gas bubble volume equals the dosed liquid volume, active control of dosed volumes can be obtained. It will be shown that the cell impedance can be applied to accurately determine the generated gas volume and that by using this parameter in a closed-loop control system, dosed volumes can be controlled in the nanoliter range.

An integrated micromachined electrochemical pump and dosing system

In this paper a micromachined electrochemically driven pump capable of dosing precise nanoliter amounts of liquid is presented. The pump consists of a micromachined channel structure realized in silicon by reactive ion etching. On top of this structure a Pyrex® cover piece with noble metal electrodes was bonded. The fluid to be dispensed is stored in a meander shaped reservoir which is part of the channel structure. This meander starts in an electrolyte solution containing reservoir, on top of which two noble metal electrodes are positioned. By the electrochemical production of gas bubbles by electrolysis of water at these electrodes, liquid can be driven out of the meander. The measured volume displacements were in close agreement with theory. Pump rates as low as a few nl/s could accurately be controlled via the actuation current through the electrodes. By applying current pulses rather than a continuous current, preset amounts of fluid in the nanoliter range could be dosed successfully. Because the resulting device consists of simple channel structures and metal electrodes it can easily be integrated in miniaturized chemical analysis systems to dose reagents or calibration solutions.

A flow-through amperometric sensor based on dialysis tubing and free enzyme reactors

A generic flow-through amperometric microenzyme sensor is described, which is based on semi-permeable dialysis tubing carrying the sample to be analyzed. This tubing (300 microm OD) is led through a small cavity, containing the working and reference electrode. By filling this cavity with a few microl of an appropriate enzyme solution, an amperometric enzyme sensor results. As the dialysis tubing is impermeable for large molecular species such as enzymes, this approach does not require any immobilization chemistry, and as a consequence the enzyme is present in its natural free form. Based on this principle, amperometric sensors for lactate, glucose, and glutamate were formed by filling cavities, precision machined in Perspex, with buffered solutions containing respectively, lactate-, glucose-, and glutamate-oxidase. All sensors showed a large linear range (0-35 mM for glucose, 0-3 mM for lactate, and 0-5 mM for glutamate) covering the complete physiological range. The lower detection limit was in the order of 15-50 microM. Applicability in flow injection analysis systems is demonstrated.

A bi-directional electrochemically driven micro liquid dosing system with integrated sensor/actuator electrodes

In this contribution a micro liquid dosing system is presented, which allows bi-directional manipulation of fluids (i.e. pushing out and pulling in of liquids) by the electrochemical generation and removal of gas bubbles. Bi-directionality is obtained by reversal of the actuation current thereby causing the earlier produced gasses to react back to water. This reduction of gas volume actively pulls liquid back into the system. The electrochemical actuator electrodes have been specially designed to perform the simultaneous measurement of conductivity, via which the total amount of gas can be estimated. As this amount equals the total dosed volume of liquid, dispensed volumes can be determined on-line during experiments.

A micromachined double lumen microdialysis probe connector with incorporated sensor for on-line sampling

In this paper, a micromachined double lumen microdialysis probe connector for on-line, in-vivo sampling is presented. The connector forms an integral part of a double lumen type microdialysis probe and guides the flow of sample fluid (‘dialysate’) directly into a flow cell with space for integrated sensors. Basically, the connector is a sandwich construction of two, multistep KOH etched silicon wafers which, after bonding allows the easy insertion of two concentric fused silica capillaries, required to construct the probe. For the experimental evaluation of the performance, in this work, a chloride selective sensor was integrated in the flow cell of the connector to continuously measure the chloride concentration in the dialysate flow. It will be shown that by adopting micromachining techniques, the induced lag time of the measurement can easily be decreased by a factor of more than 5, as compared to a conventional probe connected to a flow-through sensor. Another benefit of the proposed direct coupling of double lumen microdialysis probes and microfluidic structures in silicon, is the fact that all critical fluidic connections, especially the probe/sensor connection, are kept inside, making the microanalysis system more rigid.

A flow-through cell with integrated coulometric pH actuator

A flow-through cell with integrated coulometric actuator capable of controlling the pH of a flowing liquid is presented. The cell, consisting of a rectangular channel with a noble metal actuator electrode deposited on the bottom, enables the titration of a moving liquid without the need for pumps and reservoirs of titrant because strong acid or base is produced in situ by the electrolysis of water at the electrode surface. To ensure a homogeneous liquid at the end of the system, convectional and diffusional mass transport processes are described. Also an expression for the final pH is derived. Measurements were carried out with a flow through system having an integrated actuator electrode and pH sensitive ISFETs. The experimental results for the final pH change and mixing times were according to theory. The resulting component can be integrated in miniature chemical analysis systems for providing ‘buffer on demand’ or for on-line titration purposes.

Manufacturing of self-priming plastic micropumps

Micropumps will be key components in tomorrow’s miniaturized chemical analyzers and drug delivery systems as well as in consumer products. In this paper a recently developed plastic micropump that was manufactured using conventional technologies, i.e. injection molding, is described. By applying well known techniques and ‘off the shelf’ materials flexible and economic fabrication of micropumps for various applications is feasible even at low production volumes. The resulting pumps were self-priming and pump liquid at flow rates up to 2 ml/min and gases at around 4 ml/min. The maximum back-pressure reached is 125 hPa.

A μTAS Based on Microdialysis for On-Line Monitoring of Clinically Relevant Substances

For the monitoring of various clinically relevant substances such as glucose, lactate and electrolytes a μTA8 based on microdialysis is under development. Two modules needed in this analysis system will be presented. One component of the system is an integrated microdialysis probe that is connected with an extremely low dead volume to a channel system in silicon. This small dead volume is an important requirement for microdialysis based measurement systems because flow rates are as low as 0.2–2 μl/min. A part of the integrated channel system is in contact with an array of cavities having internal metal electrodes. These cavities can be filled with for instance an ion selective filling or a hydrogel containing enzyme contacting the dialysate stream via a liquid-liquid junction. The resulting ion-selective or enzymatic micro sensors can be applied for on-line analysis of the sample stream coming from the microdialysis probe.

A Closed Loop Controlled Electrochemically Actuated Micro Dosing System for in Situ Sensor Calibration

In this contribution a closed loop controlled electrochemically actuated micro dosing system is presented, which accurately doses calibration liquids in microsystems for the in-situ calibration of chemical sensors. The system comprises an electrolyte filled reservoir with platinum electrodes, connected to a meander channel filled with the appropriate calibrant. By the electrochemical production of gas bubbles in the electrolyte filled reservoir, this calibration liquid can be driven out into a carrier channel that leads to the sensor(s) to be calibrated. Closed loop control of actual dosed volumes is obtained by determining the total generated gas bubble volume via an impedance measurement in the electrolyte reservoir. In this work, a conductivity sensor integrated in the carrier channel of the dosing system is calibrated as an example.