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Electromagnetic Waves, Airlie, VA, Oct. 30-Nov. 4, 1977, have resulted in uneven heating of RBC's in some portions of be published. to 41.50C at the sample. The increased loss of both Hb and K+ [111 P. J. Staples and P. F. Griner, "Extracorporeal hemolysis of clearly demonstrates that such local heating could alter the blood in a microwave warmer," New Eng. J. Med., vol. 285, pp. 317-319, Aug. 1971. results obtained in these experiments. These problems were holder sample largely solved by introduction of the rotating because it assured that each tube would receive equivalent exa David J. Peterson was born in Salt Lake City, posure of microwave irradiation intensity and also it provided UT, on May 3, 1953. He received the B.A. sample mixing within each tube. degree in biology and the M.S. degree in bioX engineering from the University of Utah, Salt Lake City, in 1977 and 1978, respectively. REFERENCES While at the University of Utah, he was [1] S. Baranski, H. Ludwicka, and S. Szmigielski, "The effect of engaged in research involving the biological

[2]

[3]

[41 [5] [6] [7]

[8]

[9] [10]

microwaves on rabbit erythrocyte permeability," Medycyna Latnicza Z., vol. 39, pp. 75-79, 1971. S. Baranski, S. Szmigielski, and J. Moneta, "Effects of microwave irradiation in vitro on cell membrane permeability," in Biologic Effects and Health Hazards of Microwave Irradiation-Proc. Int. Symp. Warsaw, Poland: Polish Medical Publ., 1974, pp. 173-177. E. S. Ismailov, "Mechanism of the effect of microwaves on the permeability of erythrocytes for potassium and sodium ions," Biol. Nauki (USSR) (English translation), vol. 3, pp. 58-60, 1971. P. E. Hamrick and J. G. Zinkl, "Exposure of rabbit erythrocytes to microwave irradiation," Radiation Res., vol. 62, pp. 164168, Apr. 1975. L. M. Liu and S. F. Cleary, "Effects of microwave irradiation on erythrocyte membranes," in Abstr. 1977 nt. Symp. Biol. Effects Electromagnetic Waves, 1977, p. 103. T. C. Rozzell, C. C. Johnson, C. H. Durney, J. L. Lords, and R. G. Olsen, "A nonperturbing temperature sensor for measurements in electromagnetic fields," J. Microwave Power, vol. 9, pp. 241-249, 1974. E. A. Kabat, Experimental Immunochemistry, 2nd ed. Springfield, IL: Thomas, 1961, ch. 4, p. 149. H. Jasik, Antenna Engineering Handbook. New York: McGrawHill, 1961, ch. 10. C. C. Johnson and A. W. Guy, "Nonionizing electromagnetic wave effects in biological materials and systems," Proc. IEEE, vol. 60, pp. 692-718, 1972. 0. P. Gandhi, M. J. Hagmann, and J. A. D'Andrea, "Some recent results on deposition of electromagnetic energy in animals and models of man," presented at the 1977 Int. Symp. Biol. Effects

effects of electromagnetic waves and in treatcancerous tumors with induced hyperthermia from microwaves. He is currently serving as a Consultant to the Research Division, Northwest Energy Company.

ing

Lester M. Partlow was born in Camp Forrest, TN, on January 14, 1943. He received the B.S. and Ph.D. degrees from the Thomas C. Jenkins Department of Biophysics, The Johns Hopkins University, Baltimore, MD, in 1964 and 1969, respectively. He also spent two years as a Postdoctoral Fellow in the Department of Pharmacology, College of Medicine, Washington University, St. Louis, MO. He joined the Department of Pharmacology, College of Medicine, University of Utah, Salt Lake City, in 1972 and is now an Associate Professor. He is currently engaged in research in the areas of microwave bioeffects, neurochemistry, and neurophysiology. In addition, he teaches basic pharmacology, neuropharmacology, and neurochemistry to both medical and graduate students. Dr. Partlow is a member of Sigma Xi, the Society for Neuroscience, and the American Society for Neurochemistry.

Om P. Gandhi (S'57-M'58-SM'65-F'79) for a photograph and biography, see this issue, p. 404.

Communications INTRODUCTION

A Pulse Height Analyzer for Displaying Coulter Counter Particle Size Distributions

The Coulter counter' is widely used in medical and biological laboratories for counting and sizing cells and microorgaS. J. RACKHAM AND R. A. SHERLOCK nisms (e.g., see [1] ). In its basic form, the instrument counts the number of particles in a preselected size range in a sample volume of fluid suspension. However, much more useful inAbstract-A 100-channel pulse height analyzer for displaying particle formation about the distribution of particle sizes present can size distributions from the output of a ZBI Coulter counter has been be obtained by feeding the pulse train produced by the counted built using readily available low cost IC's. An outline of the complete particles into a multichannel pulseheight analyzer. system is presented along with a detailed description of the input pulseIn this paper we give an outline description of a 100-channel width discriminator essential in this application. pulse height analyzer designed for use with a completely standard model ZBI Coulter counter (the output pulse train being accessible via a rear panel connector on the ZBI). The analyzer Manuscript received December 22, 1977; revised December 6, 1978. S. J. Rackham was with the Department of Physics, University of can accumulate up to 106 counts in each channel; the chanWaikato, Hamilton, New Zealand. He is now with the Ministry of Agri- nels being individually addressable via a thumbwheel switch, culture and Fisheries, Ruakura Agricultural Research Center, Hamilton,

New Zealand. R. A. Sherlock is with the Department of Physics, University of Waikato, Hamilton, New Zealand.

'Manufactured by Coulter Electronics Ltd., Coldharbour Lane, Harpenden, Herts., England.

0018-9294/79/0700-0436$00.75 O 1979 IEEE

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and their contents read out on a six digit channel count light emitting diode (LED) display. The pulse height distribution can be displayed on a CRO (and can be observed "building up" as data accumulates) and can also be outputted to a Y-T or X-Y plotter. The analyzer uses standard CMOS logic almost exclusively and has been built for a parts cost of only $400, $150 of which is accounted for by a commercial analog-todigital converter (A/DC) module. The design features are discussed in detail and full circuit information given elsewhere [2]. We note here however that microprocessor techniques were considered inapplicable at the time the instrument was designed on account of the processor speed needed to cope with sample update rates of up to 5 kHz and the maintenance of a real-time CRO display, channel, and total counter displays. Even with the higher speed 16-bit devices now available, the software development would be far from trivial and probably not warrant the effort unless considerable post-aquisition processing within the same instrument was required.

counts in distributions obtained by the analyzer may vary greatly, some means of scaling this analog output is necessary. This is accomplished by selecting two adjacent BCD digits from the channel count data bus and inputting them to the 8-bit channel count DAC. The scale factor, determined by the pair of digits selected, is switched manually. The channel number DA C provides the X-input signal for the CRO. If the address on the channel address bus corresponds to the channel number selected by the thumbwheel switch, the bus comparator causes the channel count to be latched into the channel count latch and displayed on the channel count LED display. The bus comparator also drives a cursor on the CRO display; this is achieved by strobing the channel count DAC into saturation at the selected channel, thus enabling easy identification of channel positions. The plotter display is implemented by simply slowing down the channel display counter and gating it such that it makes one complete cycle only through all memory locations.

PRINCIPLES OF OPERATION A block diagram of the complete analyzer is shown in Fig. 1. Names in italics (e.g., memory) refer to units in this block diagram. During operation the analyzer is either updating channel counts (memory update cycles) or simply reading channel counts from memory for display purposes (display cycles). The memory (implemented with three 128 X 8-bit RAM's) contains the 100 six digit (24-bit) binary-coded decimal (BCD) numbers corresponding to the accumulated counts in each channel.

B. Memory Update Cycles

A. Display Cycles Most of the pulse height analyzer's time is spent implementing CRO display cycles which occur at the rate of 104 channels/s; thus, every channel is accessed 100 times/s. The memory channel count locations are addressed sequentially by the channel display counter and the corresponding channel counts are loaded from memory into the six digit BCD counter. The channel count DAC generates an analog signal proportional to the channel count in the six digit loadable BCD counter and is used to drive the CRO Y-input. Since maximum channel

When an acceptable pulse from the Coulter counter has been detected and its height converted to a two digit BCD number by pulsewidth discriminator and A/DC, timing and control is alerted. (Note that an A/DC with high differential linearity is required to ensure that all channels are of equal width.) The current display cycle is interrupted and the digitized height of the newly acquired pulse (i.e., the address of the channel in which the pulse "belongs") is gated to the memory address input. The corresponding channel count is loaded from memory into the six digit loadable BCD counter which is then incremented by one. The updated channel count is then read back into the same memory location via the tristate buffers and the displaced display cycle restored, thereby completing the memory update cycle. The 8-digit total counter accumulates the total number of counts in all channels with index numbers greater than or equal to the value set on the total count discriminator. This can be preset (by a front panel switch) to channel numbers 0, 10, 20, or 40; its purpose is to gate out lower channel noise counts which are characteristic of Coulter counter pulse height distributions (see Fig. 2).

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(b) Fig. 3. (a) Block diagram of analyzer analog input circuitry. (b) Detailed schematic of input pulsewidth discriminator: IC1 = LM339, IC2 = MM74C04, IC3 = MM74C02, IC4 = MM74C74, IC5 = LM311, and IC6 = LM311.

PULSEWIDTH. DISCRIMINATOR AND A/DC The differentiator action of the model ZBI Coulter counter tends to accentuate random current fluctuations at the transducer output, resulting effectively in a relatively large number of small amplitude (< 5 percent of max) pulses in the ZBI output. These "noise pulses" give rise to large numbers of counts in the low channels (e.g., see Fig. 2) and it is essential to prevent the analyzer's processing time being swamped by them. Fortunately, a large proportion of the noise pulses are of rela-

tively short duration (< 5 jus) compared with those arising from typical biological "particles" and, hence, can be edited out by a pulsewidth discriminator. The discriminator allows only pulses whose widths lie within a preset range to be accepted by the analyzer. A block diagram of the analog input circuitry is shown in Fig. 3(a) along with a detailed schematic of the pulsewidth discriminator in Fig. 3(b). When an "acceptable" pulse is recognized by the discriminator, a cycle of the sequencer (an eight state counter whose prime task is the control of the

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A/DC) is initiated. When the A/D conversion is complete timing and control is alerted and the sequencer is reset. The seven control signals shown in Fig. 3(a) perform the following functions. 1) "Peak detect" switches the peak detector from the tracking to the peak detect mode (Fig. 4). 2) "Hold" causes the sample and hold to be switched to the hold mode (Fig. 4.) 3) "Sequencer reset" initiates one cycle of the sequencer by going to logic 0 when an acceptable pulse has been detected by the discriminator. 4) "Sequencer Last State" signals the discriminator that the sequencer has completed its cycle. The discriminator then resumes control and resets the sequencer by returning sequencer reset to logic 1. 5) "'Start convert" initiates an A/D conversion. 6) "A/DC ready" informs pulse height analyzer timing and control that a pulse height has been converted to a channel number. 7) "EOC" signals the sequencer that the A/D conversion is complete. The pulsewidth discriminator circuitry is shown in Fig. 3(b). When the programmable gain amplifier output rises above the small input threshold voltage VT ICla ( CA 339 open collector output comparator) "floats" its output and Cl charges through R1 until the incoming pulse falls below VT, at which

point C1 is rapidly discharged (see Fig. 5.) The maximum voltage transferred to Cl provides a measure of the pulsewidth and the front panel adjustable thresholds V1 and V2 on the voltage window comparator (IClb and IClc) set the pulsewidth discriminator upper and lower thresholds (T1 and T2). The comparator IC 1 d generates a rising edge as C1 is reset and it clocks the output of IC3a onto IC4a. If the output of the window comparator was at logic 1 (+5 V) just before Cl was reset (i.e., T, < T < T2, "acceptable pulse") then a logic 1 would be clocked onto Q (IC4a) and sequencer reset would initialize a sequencer cycle, otherwise no action would occur. IC3a, R2C2, and IC3b serve two purposes. 1) They delay the window comparator output such that the value it held at the time C1 was discharged is presented to the D input of IC4a as it is clocked. 2) They smooth the 400 ns "glitch" generated as C1 is reset for the case T > T2 [see Fig. 5(a)] . As soon as IC4a is set it is "locked" into this state by IC2b and can only be "unlocked" by the sequencer last state signal (via IC2a). Note that the unlocking involves a transition via the "illegal" Q = 0, Q = 0 state and relies on MM74C74 "illegal state" characteristics. The RS flip-flop (IC3c and IC3d) prevents the pulsewidth discriminator from reinstating the sequencer until no pulses are present at the pulsewidth discriminator input. This prevents a second sequencer cycle immediately following the first

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and not allowing time for the sample and hold to acquire the new pulse height. The operation of hold and peak detect signals is illustrated in Fig. 4. The necessary overlap between these two signals is generated by the pulse stretcher D2, C3, and R 3. REFERENCES [11 H. E. Kubitshek, "Counting and sizing micro-organisms with the Coulter counter," in Methods in Cell Biology, J. R. Norris and D. W. Ribbons, Eds. London, England: Academic, 1969, pp. 593-610. [21 S. J. Rackham, "A pulse height analyzer for displaying particle size distributions," M.Sc. thesis, Univ. Waikato, Hamilton, New Zealand, 1977.

Proposed Cardiac Pacemaker System Combining Unipolar Stimulation with Bipolar Sensing

PHILIP HURZELER, V. DE CAPRIO, AND S. FURMAN Abstract-Present cardiac pacemaker designs use either unipolar or bipolar electrode systems. Advantages of unipolar electrodes for stimulation are listed; then arguments in favor of bipolar electrodes for sensing are cited. A proposed system combines unipolar stimulation with bipolar sensing and may be implemented by adding a differentialinput stage to the sensing amplifier.

STIMULATION In unipolar stimulation, while the cathode is in contact with the myocardium and connected to the pulse generator through an insulated lead wire, the anode forms part or all of the exterior package of the implanted pulse generator and, being relatively distant from the myocardium, is the "indifferent" electrode. The significant voltage loss that is characteristic of anodes during stimulation, is minimized by the large anodal surface area. In bipolar stimulation, where the anode is also in the heart and must be kept physically small, voltage stimulation thresholds are greater [ 11. Further advantages of unipolar stimulation are increased reliability due to absence of a lead wire, and avoidance of anode-to-myocardium contact with conceivable attendant fibrillation hazard [ 2 1.

SENSING For sensing of myocardial depolarization to achieve noncompetitive pacing, bipolar electrodes offer the advantage of improved rejection of electromagnetic and skeletal muscle artifact due to a more restricted lead field or "antenna" [3]. Chatterjee et al. [41 report greater signal-to-noise ratios for both ventricular and atrial sensing, using their new catheter with bipolar electrodes. Ongoing research at this institution also suggests that the bipolar signal is greater than the unipolar signal in amplitude, unless the bipolar axis is perpendicuManuscript received February 23, 1976; revised December 11, 1978. This work was supported in part by the United States Public Health Service under Grant HL 04666-16. P. Hurzeler is with Cardiac Datacorp, Inc., Bloomfield, CT 06002. V. De Caprio is with Becton-Dickinson, Inc., Fairfield, NJ 07006. S. Furman is with the Division of Cardiac Surgery, Montefiore Hospital and Medical Center, New York, NY 10467.

lar to the direction of propagation of the depolarization wave. However, new bipolar electrode geometries such as coaxial or tripod arrangements suggested by Siegel et al. [5] may be devised to overcome the directionality problem. A past constraint on such designs has been a minimum surface area of some 10 mm2 for the proximal electrode since it is also the stimulation anode. THE COMBINATION In the proposed system, one pole, say the tip, of an intracardiac bipolar electrode serves as both the stimulation cathode and as a sensing electrode, as in conventional systems. The other half of the bipole is connected only to the other input of the differential sensing amplifier, while an indifferent electrode serves as the stimulation anode. In this way the advantages of both systems are retained. An alternate way to effect the combination is to use the isolation afforded by an output transformer in the pulse generator in lieu of a push-pull differential stage in the input amplifier. As the second half of the bipole is no longer used as an anode, its surface area may be made as small as is convenient, and designs featuring hooks to attach catheter tips to the myocardium, such as described by Irnich [11, may be more valuable. A central tip, forming one pole, surrounded by a tripod of hooks forming the other pole, may overcome the directionality problem as well as avoiding dislodgement. This combination should be particularly helpful for atrial sensing. In conventional designs, the sensing amplifier input impedance is shunted by the OFF output impedance of the stimulator circuit, whereas in the proposed design the differential input impedance is not shunted. This further removes contraints on sensing electrode surface area. Also, the polarization voltage that persists after each stimulus pulse is conducted directly to a conventional single-ended sensing input, whereas in the proposed design the anodal portion of the polarization voltage, which Irnich [1I1 suggests is 'the larger portion in bipolar systems, appears as a common-mode input voltage. A further advantage is that a redundancy feature of the bipolar system is retained, to wit-in the event of a single lead wire fracture, the surgeon has the option of changing to a unipolar configuration to maintain pacing without implanting a new electrode. Finally, the concept need not be confined to systems which sense and stimulate from the same electrode tip. For instance, bipolar atrial sensing may be combined with unipolar ventricular stimulation. REFERENCES [1] W. Irnich, "Engineering concepts of pacemaker electrodes," in Advances in Pacemaker Technology, M. Schaldach and S. Furman, Eds. New York: Springer-Verlag, 1975.

[2] T. A. Preston, "Pacer induced ventricular tachycardia," in Modern

Cardiac Pacing, S. Furman and D. J. W. Escher, Eds. Bowie, MD: Charles Press, 1975. [31 A. R. Kahn and R. J. Schlentz, "Design and construction methods for protecting implanted cardiac pacemakers from electromagnetic interference," in Cardiac Pacing, H. J. Thalen, Ed. Assen, The Netherlands: Van Gorcum, 1973. [4] K. Chatterjee, H. J. C. Swan, W. Ganz, R. Gray, H. Loebel, J. Forrester, and D. Chunette, "Use of a balloon-tipped flotation electrode catheter for cardiac monitoring," Amer. J. Cardiol., vol. 36, pp. 56-61, 1975. [5] L. Siegel, E. B. Mahoney, J. A. Manning, and S. Stewart, "Conduction cardiograph-bundle of His detector," IEEE Trans. Biomed. Eng., vol. BME-22, pp. 269-274, July 1975.

0018-9294/79/0700-0440$00.75 © 1979 IEEE