Chapter 21
Thick-Film Multilayer Ion Sensors for Biomedical Applications Salvatore J . Pace and James D. Hamerslag
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Medical Products, Glasgow Site, Box 509, P.O. Box 6101, Ε. I. du Pont de Nemours and Company, Newark, D E 19714-6101
Planar format thick film ion sensors have been designed for biomedical applications. The multilayer sensor structure consists of layers sequentially deposited on a ceramic substrate using a screen printing process. All layers are of solid composition with the uppermost chemically active layer consisting of polyvinyl chloride (PVC). Because no aqueous layers are used in the construction, the resulting devices are stable and robust. The PVC layer serves as a common membrane vehicle for a multitude of ion specific ligands that may be patterned on a substrate. This paper describes the chemical and electrochemical principles of design, construction and measurement of ion sensing devices for blood electrolytes; K , Na , Cl , HCO -, pH and the potential for many other clinically significant tests. The more pragmatic issues of packaging design and materials of construction are treated in the context of device performance (i.e., analytical efficacy, reliability and stability) for the biological application intended. +
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There exists a need for reliable, low cost chemical sensors for clinical diagnostic applications and, in particular for, the management of patients undergoing a medical crisis. The demands for cost containment and more effective delivery of health care has added a premium on innovative technology. What is needed is the ability to respond quickly to the diagnostic demands of physicians at the patient's bedside. Among the most frequently requested tests are blood electrolytes (Na , K*, CI' and HC0 ) for both routine clinical profiling of blood serum and for the more critical emergency situations. We have already reported on the design of blood gas sensors based on similar design and discussed strategies for enzyme and immunosensor structures encompassing the principles of design and construction^ described in this article. This report focuses on a planar format multilayer ion sensor structure, assembled by a thick film printing process. All materials of construction are of solid composition and no aqueous layers are employed. +
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The chemically active, ion specific layer consists of a polyvinyl chloride (PVC) film in direct contact with the sample. The PVC membrane is tailored for 0097-6156/92/0487-0261$06.00/0 © 1992 American Chemical Society
Edelman and Wang; Biosensors and Chemical Sensors ACS Symposium Series; American Chemical Society: Washington, DC, 1992.
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selective ion detection and may be patterned to achieve a multitude of tests within a single device. A unique feature of this electrochemical device is the absence of aqueous gel layers conventionally applied to stabilize interfacial potentials. Attempts to stabilize the interface between die solid conductor and the polymer membrane has proven illusive for Ion Sensing Field Effect Transistors (ISFET's), yet it is well recognized in the art that the key to technological success rests on the ability to effectively transfer electrical charge across an electrical/chemical (or heterogeneous) interface without effectively altering its potential. The sensors described below are stable chemical to electrical transducers, they are robust, amenable to large scale manufacture and with appropriate patterning of membranes can enable chemical profiling of biological fluids for a variety of medical applications.
Downloaded by TUFTS UNIV on November 22, 2016 | http://pubs.acs.org Publication Date: April 23, 1992 | doi: 10.1021/bk-1992-0487.ch021
Experimental
The multilayer sensor structure consists of cermet and polymer based layers sequentially deposited on a 96% alumina ceramic substrate using a thick film screen printing process. The cermet layers are of ceramic-metal composition which require firing at a temperature of 850°C and the polymer layers are cured at temperatures below 100°C. Layout of this multilayer sensor structure is shown in Figure 1.
Figure 1. Layout of planar multilayer sensor
The sensors were fabricated using a manual thick film screen printer, a convection oven and a box furnace. The order in which the layers were deposited on the ceramic substrate is illustrated in Figure 2 and their composition characterized Edelman and Wang; Biosensors and Chemical Sensors ACS Symposium Series; American Chemical Society: Washington, DC, 1992.
21. PACE & HAMERSLAG
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Thick-Film MultUayer Ion Sensors
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in Table I. The fabrication sequence is described follows: 1) The conductor layer was printed and dried at 150°C for 15 minutes. 2) The dielectric layer, made by two print/dry steps, was printed and dried at 150°C for 15 minutes. 3) The substrates were then fired at 850°C for 10 minutes. 4) The interfacial (carbon) layer was printed and dried at 100°C for 60 minutes. 5) The membrane (PVC) layer, made by two print/dry steps, was printed and dried at 50°C for 60 minutes. This last step was repeated for each of the different membrane formulations.
Figure 2. Cross section of sensor
The P V C membrane compositions consist of a neutral carrier and ion exchange ionophores as indicated in Table I. The K membrane includes valinomycin as the ionophore and is plasticized by 2-ethyl-hexyladipate (Fluka). The N a membrane contains methyl monensin and tris(2-ethylhexyl)phthalate. Tri-ndodeclyamine is the ionophore for pH and tridodecylmethyammonium chloride is the ion exchanger for CI". HC0 * utilizes 4-butyltrifluorophenone for C 0 " detection as well as trioctylammonium chloride ion exchanger. Both anion membranes are plasticized with dioctyladipate. +
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A test system, controlled by personal computer (PC), was developed to evaluate the performance of the sensors. A schematic of this system is shown in Figure 3. The signals from the sensors were amplified by a multi-channel electrometer and acquired by a 16 bit analog to digital data acquisition board at a resolution of 0.0145 mV/bit. The test fixture provided the electrical and fluid interface to the sensor substrate. It contained channels which directed the sample, reference and calibrator solutions over the sensors. These channels combined down stream of the sensors to form the liquid junction as shown in Figure 1. Contact probes were used to make electrical connection to the substrate. Fluids were drawn through the test fixture by a peristaltic pump driven by a stepper motor and flow of the different fluids was controlled by the pinch valves. The assay protocol consisted of a single two point calibration to determine the slope of each sensor and a one point or offset calibration prior to each assay measurement. The two point calibration was conducted as follows. Reference solution was pumped into channel 1 (Figure 1), calibrator 1 into channel 2 and the response of the sensors was measured. Calibrator 2 was then pumped into channel
Edelman and Wang; Biosensors and Chemical Sensors ACS Symposium Series; American Chemical Society: Washington, DC, 1992.
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Table L Sensor composition
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LAYER
DESCRIPTION
THICK [um]
1 Conductor Ag
DuPont QS175
17
2 Dielectric
DuPont QS482
34
3 Interfacial Carbon DuPont 786ID
10
4 Membrane
10
Glass
PVC Κ* Na* CI "
i l 2 , i s
*
0 0 , n )
HC0
