Understanding the Human Machine - A Primer for Bioengineering - Max E. Valentinuzzi

creases and declining costs. Digital image processing algorithm research also continues at fast pace, spurred on by increasing commercial demands. When coupled with an expanding applications base, digital image processing techniques are becoming key tools in diverse new industries.

The interested student may find detailed background material in the classic books by Castleman (1979), in Gonzalez and Woods (1992) and in Glasbey and Horgan (1995). Also, he/she may check papers such as Chalama and Kim (1997) and/or Chittaro (2001).

Emilce Moler was born in La Plata, Argentina. She received the undergraduate degree in Mathematics and the Master of Sciences from the Faculty of Sciences of the Universidad de Mar del Plata, Argentina, in 1983 and 1995, respectively. She joined the Department of Mathematics of the same university in 1987, where she is currently Assistant Professor of Computing and Image Processing. In 1988, she became also member of the Signal Processing Laboratory of the Department of Electronics. Recently, Emilce obtained the PhD degree at the Universidad Nacional de Tucumán with a dissertation supervised by the author of this book. Her research interests include image segmentation and mathematical morphology with applications in biomedicine.

3.7. Concluding Remarks of Chapter 3

Physiological signals have been reviewed to introduce the student to this rich set full of invaluable information. Bioelectric events were arbitrarily divided in non-traditional and traditional signals, the former originating in the eye, the skin and the oocyte, while the latter have their respective stems in the heart, brain and muscle. Signals related to bioelectric events are the biomagnetic ones (such as the magnetocardiogram, magnetoencephalogram and magnetomyogram) and the bioimpedancimetric signals derived from changes in a bioimpedance. Thereafter, we moved on to biohydraulics, with its two main representatives: blood pressure and blood flow. Heart sounds, perhaps finding opposition from some people for their inclusion in this section, were considered as a paraphenomenon of the biohydraulic event. Section 3.4 dealt with biomechanical signals. In them we included force, length, torques, acceleration, surface tension, mostly generated by muscles in general. Biomaterials, cells and tissues are signal sources that do not seem to comply with traditional and more commonly handled concepts, but they do exist and are responsible for

quite a revolution in the biomedical sciences. Their signals are mostly of chemical nature. Their characterization, however, may not be an easy task. The chapter is closed with a brief description of the signals produced by an image, perhaps the most powerful form to transmit information. The thermic signal was not described. Its use is mostly limited in the detection of breast cancer using infrared sensors. Unfortunately, it is also used in war to locate enemies in dark or foggy environments.

Chapter 4

Signal Pick Up

by Carmelo J. Felice, Rossana E. Madrid and Max E. Valentinuzzi

Physiologists and biomedical engineers are very much like the fisherman, who throws the line as far and as deep as possible to catch the known and also the unexpected piece.

4.1. Introduction

Once the signal is identified, the task is to pick it up in order to study it at leisure, to characterize it and sometimes to better determine its true source. It may not be an easy enterprise. History of science has taught us several sweat-and-blood examples, as the nerve action potential and arterial pressure, to mention only two. Obviously, a gadget is required, something equivalent to the fishpole-fishhook-bait assembly. This is exactly what electrodes, sensors, transducers and biosensors are for.

The latter three words are often used interchangeably, however, they have slightly different meanings. Strictly speaking, a sensor just detects the signal under the original type of energy (electrical, mechanical, thermic, magnetic, chemical, luminic) while the transducer only transforms the small amount of energy (whatever the type) contained in a signal into another type of energy, the second usually being electrical. Thus, it literally “translates”; but it needs a sensor. However, the sensor proper is often so well immersed in the transducer as to make it essentially impossible to dissect them out. Electrodes are specific electrical sensors; in a way, they might be considered as electric-electric transducers because their input signal is in the form of electrical energy and the output is also of the same kind. A biosensor, as its prefix indicates, includes in it some kind of biological material, as for example an enzyme, which reacts with an external substrate to catalyze the production of a given substance that,

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in turn, generates a transducible signal. The whole may turn into a semiconductor chip. The final output will be always electrical. Many textbooks on bioinstrumentation have dealt with this relatively new and still developing subject.

Herein, the objective is to introduce the student to another section of the biomedical engineering world recalling, from the very starting line, that no recording system can be better than its picking up gage, for sensorstransducers, in general, are the bottleneck of the system. Tremendous advances have been made in the XXth century and they are still subject of research and development with new ideas being incorporated almost every day to scientific and technical knowledge. Most of this material belongs to the area of bioinstrumentation, one of the traditional and early specialties of bioengineering/biomedical engineering.

4.2. Electrodes: The Electric-Electric Transducer

This section describes and discusses the entrance gate for bioelectric signals to the electronic and computer environment. Electrodes represent such gate; they are the place where ionic currents (typical of living organisms) are transformed into electronic currents (usually circulating in technological equipments).

As mentioned in the preceding chapter and also above, by and large, physiological systems generate five types of signals, i.e., electrical, mechanical, magnetic, thermic and chemical; electrical and chemical ones have received a great deal of attention. We have referred also to biohydraulic signals; however, they do not encompass a different kind because they belong to the mechanical group.

The human being is in many respects an electric animal; ferromagnetic materials in it are only present in tracer amounts, as for example, iron in the liver. If biological magnetic fields were of higher intensity, perhaps simpler technologies would have been developed earlier. However, this is not the case, and biomagnetic fields sustained by bioelectric currents are so feeble that only within the last four decades or so high level technologies were developed to sense and transduce them adequately, as briefly described in the preceding chapter.

Very simplistically speaking, to be alive, a living organism must keep dc and ac electric potentials with currents traversing fluids and membranes, must maintain an enormous variety of biochemical reactions and carefully watch over the concentration of essential substances. Collectively, all such actions are encompassed by the term metabolism. Medical science uses the variables involved in these processes and the biomedical engineer constantly digs into them searching for better and more reliable probes, that is, sensors-transducers.

Electrodes are the front-end gadget to sense and measure electric potentials or currents. They touch tissues, usually directly but sometimes indirectly (as the case is when electrolytic bridges are interposed). For example, the ECG requires surface electrodes directly touching the patient’s skin; if membrane potential is measured, instead, a very small electrode (a microelectrode) needs to puncture the cell membrane to get in contact with the intracellular fluid. In any case, always at least two electrodes are mandatory, one of them acting as the return pathway. Sometimes, three electrodes are used, the third to electrically balance out the system. The output signal is calibrated either in volts or amperes, depending on whether voltage or current is measured. As stated already above, the electric potential or current sensed by the electrodes in fact also transduce ionic currents into electronic currents that excite the electronic input circuitry.

Electrodes can generally be classified into three groups:

1.noninvasive, or those that are applied to skin surfaces, such as conventional ECG limb electrodes or EEG scalp electrodes;

2.semi-invasive, such as nasopharyngeal and tympanic electrodes or EMG acupuncture needle-type electrodes; and

3.invasive, which include depth, grids, and subdermal needles.

The classic book by Geddes and Baker (1989) carefully describes, with examples, a wide variety of commonly used electrodes. Many are even commercially available. Sizes cover an ample range, from centimeters down to minute and sometimes rather elaborate pieces, as the case is with double–barrel microelectrodes or small multielectrodic arrays for research use in electrophysiology.

Student task: Search in the literature, or perhaps with a specialized professional, for different types of electrodes. Try to examine them identifying their parts.

In the case of biochemical reactions, even at biomolecular level, detection is indirect. Technology usually does not deal with transducers that produce chemical signals as output because it is more difficult to handle and interpret them. Chemical signals, instead, frequently via enzyme concentrations, are translated into electrical counterparts. The preceding chapter, devoted to signals, offers a variety of examples where electrodes are an indispensable requisite. We can include in them the measurement of pH, oxygen and carbon dioxide levels in blood, and also many other substances such as specific ions.

4.2.1. The Interface: Two Lion’s World

Absolutely all cases wherein electrodes pick up an electric signal fall in either of two categories: Either the sought signal is within the very close neighborhood of the electrodes themselves, as when measuring pH or bacterial concentration (Felice, Madrid, Olivera et al., 1999; Felice & Valentinuzzi, 1999), or the desired signal crosses the electrodic surface, as when recording ECG or EEG or EMG.

Both cases require good understanding of the electrode behavior when placed in touch with a biological tissue or with a cell suspension. A wellknown way to study it makes use of metallic electrodes immersed in a simple electrolytic medium, as for example, sodium chloride solution (NaCl), which is called saline solution, for short. Over the last hundred years, say from Warburg, in 1899, to Geddes, in 1997, and many other authors in-between, abundant electrochemical research has produced models to at least partially elucidate the real system. Remember that models are neither right nor wrong; they are just approximations that may describe better or worse the system under study depending on the specific conditions of the latter.

The contact region between an electrode and the surrounding medium is ill-defined; since it is located in the midst of two entirely different worlds, namely the electrolytic environment and the electronic side, or the solution and the metallic face, it was named electrode-electrolyte interface, the latter word meaning literally “between faces”. Colloquially speaking, two faces looking at each other and exchanging kisses.

How can an electrode transduce, or translate, electricity into electricity? When two stainless steel small pieces are immersed in 0.9 % NaCl and an external battery is connected to them, a measurable electric current

will circulate from the positive pole through the solution and back to the battery via the negative side; a very simple circuit, indeed. However, and to our surprise, the moving electric charges or carriers are not the same depending where in the circuit we look at. In all metallic portions such carriers are electrons, each with an equal and well-known amount of charge; instead, in the bulk of the electrolyte the carriers are Na+ and Cl– ions, also with a definite and known electric charge. In both places, the current is defined as the number of charges (in coulombs) per unit time (in seconds) and, thus, we could speak in terms of charge flow (in amperes). Since the circuit forms a closed loop, the total current sustained by the battery must be the same at any place, be it the solution, the electrodes, the wires or within the battery, each place always considered as a whole (to distinguish from current per unit cross-sectional area or current density which may differ at different points). Somewhere in the circuit carrier’s change from one type (electrons) to the other (ions) or viceversa and that critical place is precisely the electrode-electrolyte interface. There is an exchange phenomenon that consists of ions either receiving or delivering electrons. The ionic species can be as simple as the above-mentioned Na+ and Cl– or as complex as those derived from aminoacids or other biochemical compounds.

An interface is formed spontaneously the very moment an electrode is immersed in an electrolytic solution. The metal can be considered as a cloud of free electrons around positive ions fixed or attached to a crystalline network. Instead, free positive and negative ions and polar molecules that behave as orientable dipoles usually form the solution. Once the electrode is submerged in the solution, a redistribution of charges takes place on both sides of the limiting faces building up a metal-solution difference of potential. Two basic phenomena account for it,

appearance of superficial either free or induced charges, be it in excess or defect, with respect to the bulk of each face, or

formation of a layer of oriented dipoles towards the electrode surface. The complex system of charges and oriented dipoles has been named the double electric layer or simply the double layer. Another name is Helmholtz double layer, for it was this German scientist who first studied it in 1879. In the early times of this knowledge, it was thought that only two layers of charge formed such system (one positive and the other nega-

tive), thus its name. However, now it is well documented that the charge distribution is far more complex and only exceptionally is formed by just two layers. No matter how complex the distribution is, the interface region keeps an overall electrical balance; in other words, the principle of neutrality is maintained.

The electric-electric transduction concept becomes clear now with the transference of charges occurring in the double layer region (the term is still used in spite of its complex distribution). The charge transference process is one of the several electrochemical reactions that take place at the interface. Say that we look at the solution side. An ion must first arrive in the interface region. Such arrival can be due to any of three different transport processes:

-migration or drift, when the driving cause is an electric field;

-diffusion, when concentration gradients are present, irrespective of the particle having or not an electric charge; and

-convection, which happens when movement is due to temperature gradients or to mechanical stirring of the medium. Combinations of them are also possible.

Once at the interface, ions either deliver electrons to the electrode or receive electrons from it. The exchange is collectively called the oxidationreduction process (oxidation refers to loss of electrons and reduction to gain of electrons). In the case of sodium, potassium, or chloride, reduction or gain of an electron is a simple reaction. With proteins the situation appears as more complex, sometimes involving short-lived intermediate substances before reaching the final product.

Diffusion usually is directed toward the interface because the ionic concentration at the double layer is lower than in the solution bulk. This is due to the very transference, for once it takes place, the ion disappears as such, it is replaced by another species, and its concentration decreases.

Hermann von Helmholtz (1821–1894) can perhaps be considered as the first biomedical engineer; thus, a word about him should be said. It is educational. He attended the Potsdam Gymnasium showing interest mainly in physics and he would have liked to study that subject at the university. The family financial position, however, meant that higher education was conditioned to a scholarship. Such financial support was only available for particular topics and Hermann's father persuaded him to study medicine, which was supported by the government. In 1837, Helmholtz (he was 16) was awarded a grant to enter the Royal Frie- drich–Wilhelm Institute of Medicine and Surgery, in Berlin. But he had to sign a document

promising to work for ten years as physician in the Prussian army after graduating. Besides, he went into mathematics on his own and also read philosophy, particularly Kant (not easy task for a young guy, indeed). His research career began in 1841, with his dissertation. The direction taken by physiology though, based on the so-called “vital forces, was against his view, maintaining that physiology had to be set on the principles of physics and chemistry. He graduated from the Medical Institute in 1843 and was assigned to a military regiment at Potsdam, but spent all his spare time doing research. He concentrated on showing that muscle force was derived from chemical and physical principles. In 1847, he published a very important paper, Über die Erhaltung der Kraft (On the conservation of energy). Many of his ideas were based on concepts previously advanced by Clapeyron and Sadi Carnot (students: find out who they were). He demonstrated that in various situations where energy appears to be lost, it is in fact converted into heat. That paper was an important contribution and it was quickly seen as such. In fact, it played a large role in Helmholtz's career for the following year he was released from his obligation to serve as an army doctor so that he could accept the chair of physiology at Königsberg. His career progressed rapidly there, publishing important contributions to physiological optics and acoustics. He received great acclaim for his invention of the ophthalmoscope in 1851 and rapidly gained a strong international reputation. In 1852, he published his theory of color vision. In 1855, he was appointed to the chair of anatomy and physiology in Bonn. Hydrodynamics was also subject of his concern with contributions that had a strong impact, although somewhat delayed. Helmholtz agreed in 1858 to setting up a new Physiology Institute in Heidelberg and this event was mixed with some personal problems (his father’s death in 1858 followed by his wife’s in 1859). He was left to bring up two young children and within eighteen months he married Anna von Mohl, daughter of a professor at Heidelberg. Some of his most important work was carried out while he held this post in Heidelberg. He studied mathematical physics and acoustics producing a major study in 1862 that looked at musical theory and the perception of sound. In 1843, Ohm had stated the fundamental principle of physiological acoustics, concerned with the way in which one hears combination tones; Helmholtz improved it formulating a resonance theory of hearing. From around 1866, Helmholtz began to move away from physiology and towards physics. When the chair of physics in Berlin became vacant in 1870, he indicated interest in the position, which he took in 1871. A major topic that occupied Helmholtz was electrodynamics, searching for a compatibility with the principle of conservation of energy. Helmholtz devoted his life to seeking the great unifying principles underlying nature. His career began with one such principle, that of energy, and concluded with another, that of least action. He longed to understand the ultimate, subjective sources of knowledge. That longing found expression in his determination to understand the role of the sense organs, as mediators of experience, in the synthesis of knowledge. Helmholtz owed the depth characteristic of his contributions largely to mathematical and experimental expertise. He was a great scholar in the tradition of Leibniz, embracing all the sciences, as well as philosophy and the fine arts.