The method can be used for in-process control and single unit dose testing. It should find wide application in content uniformity testing because of the precise nature of the assay. For 3-methyl substituted cephalosporins the method should be stability indicating. The general method shows further promise for application to penicillins.
(15) (16) (17) (18)
LITERATURE CITED
(19)
(1) E. Bamberger. Ber., 32, 1805 (1899). (2) F. Feigl and V. Anger, Mikrochemie, 15, 23 (1934). (3) F. Feigl, V. Anger, and 0. Frehden, Mikrochemie, 15, 9 (1934). (4) F. Lipmann and L. C. Tuttle, J. Biol. Chem., 159, 21 (1945). (5) S. Hestrin, J. Biol. Chem., 180, 249 (1949). (6) U. T. Hill, lnd. Eng. Chem., Anal. Ed., 19, 932 (1947). (7) F. Bergmann, Anal. Chem., 24, 1367 (1952). (8) R. Hilf and F. F. Castano, Anal. Chem., 30, 1538 (1958). (9) A. F. Brodie and F. Lipmann. J. Biol. Chem., 212, 677 (1955). (10) 0. Cori and F. Lipmann, J. Biol. Chem., 194, 417 (1952). (11) R. F. Goddu. N. F. LeBlanc. and C. M. Wright, Anal. Chem., 27, 1251 (1955). (12) F. W. Staab, E. A. Regan, and S.E. Binkley, Presentedat the 109th National Meeting, ACS. Atlantic City, N.J., April 1946. (13) J. H. Ford, lnd. Eng. Chem., Anal. Ed., 19, 1004(1947). (14) G. E. Boxer and P. M. Everett, Anal. Chern., 21, 670 (1949).
(20) (21) (22) (23) (24) (25) (26) (27) (28) (29)
D. J. McLaughlin, J. Wilkie, and J. M. Kelly, Presented at the 138th National Meeting, ACS, New York. N.Y., September 1960. A. 0. Niedermayer, F. M. Russo-Alesi, C. A. Lendzian, and J. M. Kelly, Anal. Chem., 32, 664 (1960). J. R . Lane and P. J. Weiss, Presented at the Technicon Symposium, "Automation in Analytical Chemistry", New York, N.Y., October 17, 1966. R. S . Santoro in "Analytical Profiles of Drug Substances", Vol. 2, K . Florey, Ed., Academic Press, New Brunswick. N.J., 1972, p 334. H. E. Roudebush, Presented at the Technicon International Congress on Automated Analysis, Chicago, Ill.,June 6, 1969. Code of Federal Regulation, Title 21, Paragraph 436.205, May 30, 1974. E. H. Flynn, Ed., "Cephalosporins and Penicillins," Academic Press, New York, N.Y., 1972, pp 537, 680. 0. G. Lien, Jr., Anal. Chem., 31, 1363 (1959). V. Goidenberg and P. E. Spoerri, Anal. Chem., 30, 1327 (1958). J. W. Munson and K. A. Connors, J. Am. Chem. SOC.,94, 1979 (1972). J. W. Munson and K. A. Connors, J. Pharm. Sci., 61, 211 (1972). K. A. Connors and J. W. Munson, Anal. Chem., 44, 336 (1972). R. E. Notari and J. W. Munson, J. Pharm. Sci., 56, 1060 (1969). J. M. T. Hamiiton-Miller et al.. J. Pharm. Pharmacol., 15, 81 (1963). J. Konecny et al.. J. Antibiot., 26, 135 (1973).
RECEIVEDfor review June 9, 1975. Accepted July 21, 1975.
Continuous Monitoring Instrument for Reactive Hydrocarbons in Ambient Air Bernard E. Saltzman, William R. Burg, and John E. Cuddeback Department of Environmental Health, University of Cincinnati, Cincinnati, Ohio 45267
This modification of a total hydrocarbon analyzer made it capable of simultaneously monitoring ambient air for reactive hydrocarbons with the potential for producing photochemical smog. Metered sample air flows were contlnuously pumped through an empty column and an absorbent column arranged in parallel. The air stream exiting from each column was directed alternately in a 5-minute cycle by a switching valve to the flame ionization detector for quantltative measurements. A chromium trioxide-sulfuric acid packing was optimal to absorb olefinic and higher aromatic hydrocarbons, and suitable column dimensions, flow rates, and temperatures were determined to obtain desired separations. Reactive hydrocarbon concentrations, obtained by difference from the instrument recordings, are reported for Cincinnati. These measurements should be more relevant than those of total or non-methane hydrocarbons.
Individual hydrocarbons vary widely in their participation in the complex kinetic processes of smog formation (1-6). The relative importance of each of the approximately one hundred hydrocarbons in the atmosphere results from its individual reactivity and concentration as well as ability to form strong oxidants and lachrymators (7). The current federal ambient air quality standard and reference method are for non-methane hydrocarbons (8). However, neither total hydrocarbons nor total hydrocarbons minus methane are accurate measures of smog potential. Because of the substantial economic and legal significance, more specific and valid measurements are urgently desirable. Differential instruments have been developed for monitoring ambient air for total hydrocarbons and methane (9, IO), for selectively combusting some hydrocarbons (111, or for exhaust gas analyses (12-14). Chemical absorbents for the exhaust concentrations, however, were ineffective for 2234
the concentrations present in ambient air. The purpose of this study was to further develop a monitoring instrument for ambient air that measured as specifically as possible only the olefinic and aromatic hydrocarbons that are reactive in the processes producing photochemical oxidants. The basic work was the selection and characterization of a solid absorbent capable of absorbing each type of hydrocarbon, such as olefins and aromatics, in proportion to its degree of reactivity in the smog forming processes. Continuous monitoring of both total and reactive hydrocarbons a t ambient air concentrations was accomplished by relatively simple adaptations of available instrumentation.
EXPERIMENTAL Monitoring System. The instrument, shown schematically in Figure 1, was assembled from commercially available components: a continuous FID total hydrocarbon analyzer (Beckman Model 109A), a thermostated valve oven (Carle Model 4301) which contained a two-section absorbent column and an empty column in parallel, and a microvalve (Carle Model 2012, two-position, two stops a t 4 5 O ) which was turned by a valve actuator (Carle Model 4201) operated by a timer (Carle Model 4102 thirty-minute cycle valve minder). The Beckman instrument was slightly modified by disconnecting the sample air line from the flame detector just upstream from the capillary restrictor. This flow was diverted through the parallel columns in the oven. The exiting flow from each column was connected alternately by the microvalve back to the sample capillary tube at the base of the burner. The needle valve, 3, was adjusted to vent the exiting sample flow that was not directed to the flame at the identical rate (11 mlimin for a span of 3 ppm C). Event markers placed in the valve minder controlled the valve actuator switches a t the desired intervals. A 5-minute cycle time was chosen to correspond with the sampling frequency established for air quality data banks; although shorter cycle times are feasible, the requirements for data handling would be more complex. Thus, the flow from each column alternately was directed to the flame ionization detector for a 2.5-minute interval. In order to protect the switching valve from dust, an all-metal 13-mm diameter Millipore Swinny filter holder with a Whatman No. 41 paper
ANALYTICAL CHEMISTRY, VOL. 47, NO. 13, NOVEMBER 1975
. L_L_-
$PI -
/GET,,
Figure 1. Schematic diagram of the hydrocarbon monitoring system
filter was placed a t the outlet of each column. The three unused valve ports were capped; they were available as spares. The rotation limits of the valve required careful adjustment a t the operating temperature. Small glass columns were prepared from fi4-inch 0.d. tubing fused to each side of '&inch i.d. tubing. Two of these were connected in series into the stainless steel system with 1/4-inchSwagelok fittings and Zytel (nylon) ferrules. Teflon tubing inside the oven was unsatisfactory because some batches caused an unacceptably high background reading. The internal volume for packing was determined to be 4.4 ml for the Cr03-H~S04section and 5.2 ml for the soda-lime (CaO NaOH) scrubber section downstream from it. These columns were fitted in the oven so that both were in nearly vertical positions to minimize channeling. The dial oven thermometer, located close to the heating and control elements under the metal floor of the oven, was found to indicate 100 "C when the absorber temperature was actually a t 93 "C. Appropriate corrections were made because absorber characteristics were temperature-dependent. Hydrocarbon-free air (prepared as described below in the Standardization Procedures) and methane or ethane samples were used for setting the zero base line and instrument span controls. Three factors were found to cause the signals from the empty and packed column gas streams to be erroneously unequal during both adjustments. These were: the slow emission of reactive hydrocarbons from the diaphragm in the air pump, that had previously been absorbed from samples containing very high concentrations; reactive hydrocarbon impurities which were unwittingly present in the test gases or were desorbed from the Tedlar (polyvinyl fluoride) sample bag; and appreciable differences in the moisture content of the sample air from that to which the absorbent was previously equilibrated. Hydrocarbon emissions from the pump diaphragm were not a problem at ambient air concentrations or at higher concentrations of 1 to 4 carbon saturated hydrocarbons. A commercial cylinder of a standard mixture of ethane in nitrogen was found to contain unsaturated hydrocarbon compounds which could be removed by passing the gas through a heated column packed with the Cr03-H2S04. This gas was then saturated with moisture by passing it through a gas-washing bottle containing distilled water. A Tedlar bag was filled and flushed daily for several days before reliable low concentrations could be prepared. I n s t r u m e n t Characteristics. The modifications to the Beckman instrument increased the volume of sample air between the pressure regulator and the flame ionization detector. Since the resistance of the capillary restrictor was much larger than those of the valve, columns, and filters, the flow rate into the detector was not appreciably changed. However, the response time was slightly lengthened. The original Beckman cover was removed in the prototype instrument to make room for the new tubing, and was replaced with a heavy aluminum foil cover to prevent air currents over the detector. The noise, stability, and drift were then within the manufacturer's specifications. Initial monitoring of air near a parking lot showed rapid and wide variations in the ambient air hydrocarbon concentrations. These fluctuations, due to incomplete atmospheric mixing of nearby automobile emissions, were often 50% of scale and created problems in data evaluation. Since these high emissions would be diluted by mixing within a relacively short distance, recording of the rapid variations was not of sufficient value to justify the complicated and expensive signal-averaging electronics required to distinguish the two levels of operation. This problem was circumvented by installing a simple mixing reservoir, 2, to dampen out the rapid fluctuations. The reservoir was constructed by brazing a short length of %-inch 0.d. copper sample line into each of two
+
l'h-inch pipe caps and screwing them onto the ends of a threaded nipple. The sample lines extended a short distance into the reservoir, where they terminated in a bend to provide as much mixing as possible. Several lengths of nipple were tried. The optimal volume was determined to be 56.3 ml. A volume of 19.8 ml was the smallest which gave a sufficiently integrated sample to yield adequately smoothed curves. A bypass valve, 1, was added to reduce the response time when the instrument performance was checked. T h e detector rise and fall times (90%) when a step concentration was presented to the valve downstream from the reservoir was 13.8 seconds, a small fraction of the 2.5-minute half-cycle period. Tests of Solid Absorbents. Exploratory experiments showed that temperature, humidity, and contact time strongly affected the ability of an absorbent to remove a particular hydrocarbon from the sample stream. Propane and propene was selected for test purposes to represent the unreactive and reactive classes of hydrocarbons, for screening of candidate absorbents under comparable conditions. The desired performance was complete passage of the propane and complete absorption of the propene. The oxidizing agents tested were silver dichromate, potassium permanganate, ceric ammonium sulfate, ferric sulfate, and a chromium trioxidesulfuric acid mixture. With the exception of silver dichromate, they were coated on 60-80 mesh chromosorb W solid supports. Approximately one-tenth gram of each prepared absorbent was packed into each column. The chromium trioxide-sulfuric acid mixture was found to remove a much greater fraction of propene than the others. The sulfuric acid played an important supporting role since neither Cr03 nor H2SO4 coated alone on chromosorb absorbed olefins. Other tests on samples of ethylene, benzene, and ethyl alcohol also showed the Cr03-H2S04 absorbent to be considerably more effective. Consequently, a detailed study of this absorbent was undertaken. After continued use with higher olefinic sample concentrations, the packing changed to the green color characteristic of trivalent chromium compounds. The color change started a t the inlet and proceeded down the column with a sharp front. No color change occurred when only purified air was passed through this absorbent. The chromium trioxide-sulfuric acid mixture was thermally stable up to approximately 135 "C. At higher temperatures, there appeared to be some decomposition with deposition of a reddish brown solid on the downstream glass wool plug. T o protect the valve from acid vapors, as well as to absorb volatile oxidized organic compounds, the alkaline section was inserted in the line downstream from the oxidant section. Soda-lime alone did not absorb detectable amounts of propane. P r e p a r a t i o n of Recommended Absorbent Column. Ten grams of 60-80 mesh chromosorb W were added to 60 ml of an aqueous solution of 2.5 grams of chromium trioxide and 1.0 ml of sulfuric acid (sp gr 1.84). The water added to ensure uniform coating was evaporated over a steam bath until the remaining solid exhibited a uniform reddish pink color. The absorbent was stored in a glass stoppered bottle. About 1.6 g were required to pack the oxidant section of the column. The alkaline section contained 5 g of 12-mesh soda-lime. After sufficient time elapsed for the new column to reach the 74 "C operating temperature, moistened "hydrocarbon-free" air was passed through it a t 11 ml/min for 3 hours to properly condition the two sections before use for the first time. Effects of Humidity of t h e Air Sample. Moisture had a very marked effect on the capability of this absorbent to remove reactive hydrocarbons from the airstream. For an air sample dried by a silica gel column, the absorbent was very reactive and, a t 100 "C, even removed a high percentage of propane. Experiments conducted with samples of controlled humidity showed that the humidity of the absorbent bed was the significant factor, and that equilibration with the humidity in the sample required hours. A practical method to control ordinary variations in air sample humidity within adequate limits was to pass it through a bubbler containing water upstream from the instrumental system. When the packed column was maintained above 50 "C, it never absorbed enough moisture to change its color. Air saturated with moisture a t room tsmperature, approximately 24 OC, was used in all experiments unless indicated. The alternative approach to controlling humidity by drying the air also has merit, but was not investigated because it appeared to be more troublesome. Effects of T e m p e r a t u r e of Absorbent. Figure 2 summarizes some exploratory studies with propane and propene and shows the effects observed for temperatiire and contact time. The time the gas was in contact with the absorbent was calculated by dividing the void volume by the fluw rate. The results were obtained with a
ANALYTICAL CHEMISTRY, VOL. 47, NO. 13, NOVEMBER 1975
2235
'
c
120'C
60
0
04
08
12
I6
20
R E A C T I V E HYROCARBONS PPM
0.0
,010
015
,020
,025
,030
Differential and cumulative frequency distributions of reactive hydrocarbon concentrations shown in Figure 3
Flgure 4.
T I M E (minutes) Figure 2. Preliminary studies of effects of temperature and contact time on the absorbent performance
801
0
' 6PM
neously in the dilution system. Separate bags were reserved for methane, ethane (a commercial tank mixture in N2),and propane samples to avoid cross-contamination by desorption. The unsaturated compounds present in small amounts were removed from the ethane mixture by passing it through a heated column packed with the chromium trioxide-sulfuric acid absorbent followed by a water filled gas washing bottle for humidification. The zero and span adjustments were made with purified air and 9 ppm methane. Then the condition of the absorbents was checked with 9 ppm C standards of propane and of propene by comparing responses in alternate positions of the microvalve. It was required that more than 99% of the propane and less than 1% propene passed through the absorbent column. Otherwise, the absorbents were replaced.
I -
8PM
IOPM
IZPM
?AM
4AM
SAM
8AM
IOAM
RESULTS AND DISCUSSION
TIME
Figure 3.
Monitor recording of ambient air in Cincinnati on June 2,
1973 Upper half of each 5-minute cycle shows total hydrocarbon concentration, and the decrease to the lower half is the reactive hydrocarbon concentration
modified gas chromatograph using a tube column packed with 0.6 g of the chromium trioxide-sulfuric acid absorbent followed by 1.0 g of 12-mesh soda-lime in its oven. Temperatures as high as 90 "C were found to be undesirable because the absorbent removed significant amounts of saturated hydrocarbons except for methane and ethane. A temperature of 70 "C sufficed to absorb concentrations as high as 200 pprn of butadiene and 100 ppm of 1-butene. When the temperature of the oven was subsequently raised to 125 O C , the absorbed products were not released, since there was no significant increase in the base line of the detector. Thus, the unsaturated hydrocarbons probably were chemically rather than physically absorbed. The color changes in the chromium trioxide and increased activity with temperatures supported the conclusion that an oxidation reaction occurred. The effect of temperature on the removal of propane showed an Arrhenius relation; however, other hydrocarbons did not follow this pattern. The complicating factor may be the dual effect of the temperature on both the reaction rate and on the moisture content of the Cr03-H&04 absorbent. A series of runs was made over a wide range of concentrations of propene t o determine if the fraction passing through the column was dependent on the concentration. It did not vary with concentrations up to 150 ppm. The optimal temperature finally selected to provide the best separation between reactive and unreactive hydrocarbons was 74 "C. This was based on tests with a variety of hydrocarbons of known importance in air pollution. Standardization Procedure. Air was purified from hydrocarbons by passage through a lys-inch 0.d. fused silica tube containing a packing of l/4 X %-inch gamma alumina tablets coated with 0.1% platinum (Chemetron Corporation, Catalysts Division, Girdler G-43) heated to approximately 1200 O C for a length of 10 inches. At flow rates of about 4.0 liters per minute, air containing 10 ppm methane, the hydrocarbon most difficult to remove was sufficiently purified to give no detectable response. Purified air was used for setting the instrument zero, for diluting standard samples in 90liter Tedlar bags, or for passage over permeation tubes. Whenever appropriate, one or more permeation tubes could be used simulta-
2236
T a b l e I shows t h e responses of t h e final i n s t r u m e n t t o a n u m b e r of i m p o r t a n t hydrocarbons for five different a b sorber temperatures. A t t h e selected optimal t e m p e r a t u r e of 74 O C , these d a t a show b o t h t h e initial performance a n d that after 4 weeks of continuous a m b i e n t air monitoring. T h e absorber showed only a small change in reactivity, a n d t h u s should have a long useful lifetime under operating conditions. Other t e m p e r a t u r e s or absorbers of different dimensions m a y be chosen t o alter t h e response spectrum of t h e instrument. T h e evaluation of t h e reactivity or importance of various hydrocarbons in smog-forming processes is complicated by aerosol formation, interactions with physical or chemical agents, synergisms, concentrations, a n d by t h e imprecisions of selecting a n d measuring adverse effects. T h e criteria that have been proposed include peak concentrations of oxidants, P A N , formaldehyde, a n d aerosols as well as eye irritation a n d p l a n t d a m a g e (15-17). Although t h e r e a r e some inconsistencies a n d difference of opinion between t h e r a t ings according t o these criteria, t h e reactivities of t h e most i m p o r t a n t hydrocarbons with our absorbent were found t o parallel their reactivities in atmospheric reactions as reasonably closely as was practical. T h e performance t o be expected with atmospheric mixtures would, of course, vary with t h e chemical composition of each, a n d can be best calculated a n d estimated from t h e d a t a in T a b l e I. An illustrative calculation was m a d e on t h e listing (18) of t h e average hydrocarbon composition in a m bient air of Los Angeles for 1965. This showed a total p p m (as carbon) of 5.43, which included 3.22 m e t h a n e , 1.28 other alkanes, 0.29 alkenes, 0.08 acetylenes, a n d 0.56 aromatics. T h e response of our reactive hydrocarbon instrum e n t estimated from t h e d a t a in T a b l e I was 0.85 pprn C. T h i s m a y be a more valid measure of t h e air quality t h a n t h e non-methane concentration of 2.21 p p m C. Improved measurements m a k e possible a d e q u t e maintenance of air quality with minimal restrictions on emissions.
ANALYTICAL CHEMISTRY, VOL. 47, NO. 13, NOVEMBER 1975
Table I. Percent Responsea to Various Hydrocarbons a t Several Absorber Temperatures Temperature ' C 74 Compounds
Saturated hydrocarbons Methane Ethane Propane 12-Butane Heptane Octane Cyclohexane Mixture-Methane) Ethane and Propane Olefins Ethylene Propylene 1-Butene 2 -Butene Isobutylene Mixture-Propylene, 1-Butene, 2-Butene Mixture-Methane, Propylene (equal molar) Acetylenes Acetylene Ethyl acetylene Aromatics Benzene Toluene J H -Xylene 17- Propylbenzene Mixture-0, i i i ,@-Xylenes Ethylbenzene and isopr opylbenzene Alcohols Ethyl alcohol Alcohol mixture2-Propanol, 2-Butanol 1-Propanol) 2-Butanol Miscellaneous Butadiene Chloroform 1,2-Dichloroethane
48
0 .o 0 .o 0.0 0.0 43 .O 79.0
2 1 .o
37
Initial
0 .o 0 .o 0 .o
0 .o 0.0 0.5
0.0 52 .O 9 1 .o 39 .O
Aftei 4 w k
E4
0.0 0.0 0.0
0.5 1.3 13.7
1.o
0.5
29.0
78 .O 99 .o 70.0
76.0 98 .O 67.0
93
0.8 2 .o 52 .O 75.0
0.2 7 .O 98 .o 97.0 95.0 64 .O
22.0 100 .o
99 .o 98 .O 74 .O
88 .O 100.0
100.0 100.0 99 .o 100.0
100 .o 100.0
86 .O 100.0 100.o 100.0 97.0
100 .o
75 .O
1.8
0.0 59 .O
3 .O 67.0
19.0 95.0
1.o 83 .O
4.9 96 .O 100.0 99.0 100.o
5 1 .O
90 .o
94 .O 5.0 94 .O
.
96 .O
100.0 99.0
100.0
100.0 100.0 100.0
100.0 2 .o 2 .o
100.o
a Percent response is defined as 100 - percent transmission through the absorber. (Percent transmission is the ratio of the reading for the sample stream from the absorber to t h a t from the bypass.)
Ambient air was monitored for hydrocarbons for more than a month from a second-story window in the laboratory. Several high levels and several low levels were compared with those from a CAMP station about 2.6 miles to the south. The values were in as close agreement as could be expected considering the distance between the sampling points. Figure 3 shows a typical recording giving the usual patterns for total and reactive hydrocarbon concentrations including elevated morning and evening levels. I t is apparent that the values exceeded Federal Standards. The morning concentrations are particularly important because they are exposed to sunlight and give rise to photochemical smog formation. The system demonstrated its ability t o follow the ambient air concentrations. The frequency distribution of reactive hydrocarbon concentrations from these data are shown in Figure 4. The most frequent concentration was 0.14 pprn and the median was 0.22 ppm. Automatic attentuation or digital recording would improve the data collection. When this instrument was oper-
ated a t 3.26 ppm C full scale for greatest accuracy, operator attention was required to manually attenuate off-scale peaks; this was even required a t the generally used full scale setting of 9.8 ppm. Loss of higher values, although rare, was of concern because of their importance.
CONCLUSIONS The chromium trioxide-sulfuric acid mixture on 60-80 mesh chromosorb was shown t o be an effective absorbent for those hydrocarbons which are important contributors to photochemical reactions. The absorber removed concentrations that were higher than ambient air levels by a factor of ten. Its performance as determined by accelerated tests and ambient air monitoring indicated that the absorber can be used for longer than a month before replacement. The absorption characteristics for classes of hydrocarbons can be adjusted by changing the absorbent column temperature or dimensions t o yield the best correlation with other measures of smog effects.
ANALYTICAL CHEMISTRY, VOL. 47, NO. 13, NOVEMBER 1975
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An air monitoring system incorporating this absorbent was readily constructed by simple modification of a common FID hydrocarbon monitor, with addition of a commercially available valve oven, switching valve, and timer. This system, except for the adjusted response time, had virtually the same operating specifications as the original hydrocarbon analyzer. Short-term studies indicated the system was practical, reliable, and accurate. Air-monitoring data obtained for Cincinnati indicated that the method could provide significant new information about air quality.
LITERATURE CITED (1) A. P. Altshuller, W. A. Lonnernan, F. D. Sutterfleld. and S. L. Kopczynski, Environ. Sci. Techno/., 5, 1009 (1971). (2) S. L. Kopczynski, W. A. Lonneman, F. D. Sutterfield, and P. E. Darley. Environ. Sci. Techno/.. 6, 342 (1972). (3) W. A. Glasson, and C. S. Tuesday, Environ. Sci. Techno/., 4, 916 ( 1970). (4) B. Dirnltrlades. Environ. Sci. Techno/.,6, 253 (1972). (5) T. A. Hecht and J. H. Seinfeld, Environ. Sci. Techno/., 6, 47 (1972). (6) S. K. Friedlander and J. H. Selnfeld, Environ. Sci. Techno/., 3, 1175 (1969).
(7) J. M. Heuss and W. A. Glasson, Environ. Sci. Techno/., 2, 1109 (1968). (8) Environmental Protection Agency, "National Primary and Secondary Ambient Air OuaHty Standards," Fed. Regis., 36, 8186-8201 (April 30, 1971). (9) A. P. Altshuller, G. C. Ortrnan, and B. E. Saltzrnan, J. Air Pollut. Control ASSOC.,16, 87 (1966). (10) R. K. Stevens and A. E. O'Keefe, Anal. Chem., 42 (2), 143A (1970). (11) W. A. King, Jr.. Environ. Sc;. Techno/.,4, 1136 (1970). (12) D. L. Klosterrnan and J. E. Sigsby, Environ. Sci. Techno;., 1, 309 (1967). (13) W. B. Innes, W. E. Barnbrick, and A. J. Andreatch, Anal. Chem., 35, 1198(1963). (14) R. H. Groth and V. A. Zaccardi, J. Air Pollut. Control Assoc., 22, 696 (1972). (15) A. P. Altshuller, J. Air Pollution Control Assoc., 16, 257 (1966). (16) A. P. Altshuller and I. R. Cohen, Int. J. Air Water Polluf., 7, 787 (1963). (17) A. P. Altshuller and J. J. Bufalinl, Environ. Sci. Techno/. 5, 39 (1971). (18) National Air Pollution Control Adrnin., Publication Ap-64, "Air Quality Criteria for Hydrocarbons." pp 3-8.
RECEIVEDfor review March 31, 1975. Accepted July 28, 1975. This work was supported in part by the Center for the Study of the Human Environment under U.S. Public Health Service Grant ES 00159, and in part by the Environmental Protection Agency under Research Grant R800869.
Potassium Ion-Sensitive Field Effect Transistor Stanley
D. Moss, Jifi Janata,' and Curtis C. Johnson
Department of Bioengineering, University of Utah, Salt Lake City, Utah 84 172
The construction and theory of operation of a potassiumsensitive field effect transistor Is described, and Its performance is characterized both as a solid-state field-effect device and as an electrochemical sensor. The performance of this device is comparable with the correspondlng PVC-type ion selective electrodes. The transistor operates satisfactorliy in the presence of proteins and it has been used for determination of potassium ion concentration in blood serum.
A new type of electrochemical sensor, an ion-sensitive field-effect transistor (ISFET), was introduced when Bergveld removed the metal gate from a metal oxide semiconductor field-effect transistor (MOSFET) and exposed the silicon oxide gate insulator to a measured solution ( I ) . A similar approach was followed later by Matsuo and Wise ( Z ) , and this new subject area has been recently reviewed by Zemel ( 3 ) .In the broader sense of chemically sensitive field-effect transistors, one sensitive to molecular hydrogen has also been reported ( 4 ) . The ISFET is a result of the integration of two technologies: ion-selective electrodes and solid state microelectronics. This development opens several new possibilities, such as miniaturization, development of multiprobes, all solidstate design and in situ signal processing. Because of its small size, it presents a difficult encapsulation and packaging problem which is, however, amply offset by the elimination of electrical pick-up noise by in situ impedance conversion and on site signal amplification. Bergveld did not modify the ion-sensitive layer in any way although he considered introducing impurities in order to render the device ion selective. In this paper, we introduce a class of devices having a chemically-sensitive layer placed over the gate region, and we report our results with valinomycin/plasticizer/poly(vinylchloride) membrane Present address, Corporate Laboratory ICI, Ltd., The Heath, Runcorn, Cheshire, England. 2238
which is selectively sensitive to potassium ion ( 5 ) .Performance of this ISFET is examined both from the point of view of a solid state field effect device and as an electrochemical sensor.
EXPERIMENTAL Integrated Circuit. A photomicrograph of the specially-designed integrated circuit chip is shown in Figure 1. The circuit was processed on a 2-inch diameter, P-type, silicon wafer having a (111) crystal orientation and 12 to 15 ohm-cm resistivity. The chip is approximately 1.28 mm X 2.13 mm and contains two ISFET transistors and two metal gate control devices. Each transistor is an N-channel depletion-mode (normally on) device with a source to drain spacing of approximately 20 gm. The transistors were intentionally made large (400 pm wide) for experimental purposes. The gate insulator consists of a thermally grown Si02 layer approximately 400 A thick and a Si3N4 layer approximately 500 A thick. The N-diffused source and drain regions are approximately 1 to 2 pm in depth and 150 pm wide. The field oxide is approximately 10,000 %, thick. Contact holes are etched in the insulating layers to allow electrical connection to be made to the source and drain diffusions. Aluminum conductors approximately 1 micron thick are formed on the surface by evaporation and photo-etching techniques. The IC chip is die-attached and wire-bonded to a 10-pin TO-5 type IC header. The chemical membrane is next applied by a solution casting technique (6). Once the membrane has cured, a quarter-inch long piece of flexible tubing is placed over the IC header. The IC header is then placed in a holding fixture at an angle of approximately 45', and encapsulant is injected into the lower portion of the IC header-tubing volume. The encapsulant used is Tra Cast 3012 (Tra-Con, Inc., Medford, Mass.) having a volume resistivity of 4.5 X 10'j ohm-cm. Once the encapsulant has cured, the IC header is rotated 90° and the encapsulant injection procedure is repeated. This process continues for a total of 4 cycles until the bonding wires and scribe lanes of the chip are totally covered by the encapsulant. Leads are then soldered to the existing pins on the TO-5 header, after which the entire unit is placed in a short glass tube and sealed with additional applications of epoxy encapsulant. Chemicals. Ion-exchange membranes were cast from T H F solutions in the following compositions: 10.0 mg valinomycin (Sigma Chemical Company), 0.89 ml dioctyladipate (K & K Laboratories,
ANALYTICAL CHEMISTRY, VOL. 47, NO. 13, NOVEMBER 1975
