Neuman. m.r.""Biomedical Ser The Electrical Engineering Handbook Ed. Richard C. Dorf Boca raton crc Press llc. 2000
Neuman, M.R. “Biomedical Sensors” The Electrical Engineering Handbook Ed. Richard C. Dorf Boca Raton: CRC Press LLC, 2000
114 Biomedical sensors 114.1 Introduction 114.2 Physical Sensors 114.3 Chemical Sensors 114.4 Bioanalytical Sensors Michael R Neuman 114.5 Applicat 114.6 Summary 114.1 Introduction Any instrumentation system can be described as having three fundamental components: a sensor, a signal processor, and a display and/or storage device. Although all these components of the instrumentation system are important, the sensor serves a special function in that it interfaces the instrument with the system being measured In the case of biomedical instrumentation a biomedical sensor(which in some cases may be referred to as a biosensor) is the interface between the electronic instrument and the biologic system. There are some general concerns that are very important for any sensor in an instrumentation system regarding its ability to effectively carry out the interface function. These concerns are especially important for biomedical sensors, since the sensor can affect the system being measured and the system can affect the sensor performance. Sensors must be designed so that they minimize their interaction with the biologic host. It is important that the presen of the sensor does not affect the variable being measured in the vicinity of the sensor as a result of the interaction between the sensor and the biologic system. If the sensor is placed in a living organism, that organism will probably recognize the sensor as a foreign body and react to it. This may in fact change the quantity being sensed in the vicinity of the sensor so that the measurement reflects the foreign body reaction rather than a central characteristic of the host Similarly, the biological system can affect the performance of the sensor. The foreign body reaction might cause the host to attempt to break down the materials of the sensor as a way to remove it. This may, in fact, degrade the sensor package so that the sensor can no longer perform in an adequate manner. Even if the foreign body reaction is not strong enough to affect the measurement, just the fact that the sensor is placed in a warm, aqueous environment may cause water to eventually invade the package and degrade the function of the sensor. Finally, as will be described below, sensors that are implanted in the body are not accessible for calibration Thus, such sensors must be extremely stable so that frequent calibrations are not necessary Biomedical sensors can be classified according to how they are used with respect to the biologic system. Table 114.1 shows that sensors can range from noninvasive to invasive as far as the biologic host is concerned. The most noninvasive of biomedical sensors do not even contact the biological system being measured. Sensors of radiant heat or sound energy coming from an organism are examples of noncontacting sensors. Noninvasive sensors can also be placed on the body surface Skin surface thermometers, biopotential electrodes, and strain gauges placed on the skin are examples of sive sensors. Indwelling sensors are those which can be placed into a natural body cavity that communicates with the outside. These are sometimes referred to as minimally invasive sensors and include such familiar sensors as oral-rectal thermometers, intrauterine pressure transduc- ers,and stomach pH sensors. The most invasive sensors are those that need to be surgically placed and that c 2000 by CRC Press LLC
© 2000 by CRC Press LLC 114 Biomedical Sensors 114.1 Introduction 114.2 Physical Sensors 114.3 Chemical Sensors 114.4 Bioanalytical Sensors 114.5 Applications 114.6 Summary 114.1 Introduction Any instrumentation system can be described as having three fundamental components: a sensor, a signal processor, and a display and/or storage device. Although all these components of the instrumentation system are important, the sensor serves a special function in that it interfaces the instrument with the system being measured. In the case of biomedical instrumentation a biomedical sensor(which in some cases may be referred to as a biosensor) is the interface between the electronic instrument and the biologic system. There are some general concerns that are very important for any sensor in an instrumentation system regarding its ability to effectively carry out the interface function. These concerns are especially important for biomedical sensors, since the sensor can affect the system being measured and the system can affect the sensor performance. Sensors must be designed so that they minimize their interaction with the biologic host. It is important that the presence of the sensor does not affect the variable being measured in the vicinity of the sensor as a result of the interaction between the sensor and the biologic system. If the sensor is placed in a living organism, that organism will probably recognize the sensor as a foreign body and react to it. This may in fact change the quantity being sensed in the vicinity of the sensor so that the measurement reflects the foreign body reaction rather than a central characteristic of the host. Similarly, the biological system can affect the performance of the sensor. The foreign body reaction might cause the host to attempt to break down the materials of the sensor as a way to remove it. This may, in fact, degrade the sensor package so that the sensor can no longer perform in an adequate manner. Even if the foreign body reaction is not strong enough to affect the measurement, just the fact that the sensor is placed in a warm, aqueous environment may cause water to eventually invade the package and degrade the function of the sensor. Finally, as will be described below, sensors that are implanted in the body are not accessible for calibration. Thus, such sensors must be extremely stable so that frequent calibrations are not necessary. Biomedical sensors can be classified according to how they are used with respect to the biologic system. Table 114.1 shows that sensors can range from noninvasive to invasive as far as the biologic host is concerned. The most noninvasive of biomedical sensors do not even contact the biological system being measured. Sensors of radiant heat or sound energy coming from an organism are examples of noncontacting sensors. Noninvasive sensors can also be placed on the body surface. Skin surface thermometers, biopotential electrodes, and strain gauges placed on the skin are examples of noninvasive sensors. Indwelling sensors are those which can be placed into a natural body cavity that communicates with the outside. These are sometimes referred to as minimally invasive sensors and include such familiar sensors as oral-rectal thermometers, intrauterine pressure transducers, and stomach pH sensors. The most invasive sensors are those that need to be surgically placed and that Michael R. Neuman Case Western Reserve University
CARDIAC MONITOR T e basic method of assessing heart function is thermodilution, a procedure that involves insertion f a catheter into the pulmonary artery and is demanding in terms of cost, equipment, and skilled ersonnel time. For monitoring astronauts in flight, NASA needed a system that was non derably less compl n 1965, Johnson Space Center contracted with the University of Minnesota to explore the then-known but little-developed concept of impedance cardiography(ICG)as a means of astronaut monitoring. A five-year program led to the development of the Minnesota Impedance Cardiograph(MIC), an electronic system for measuring impedance changes across the thorax that would be reflective of cardiac function and blood flow from the heart's left ventricle into the aorta ICG clearly had broad potential for hospital applications but further development and refinement was needed. A number of research institutions and medical equipment companies launched development of their own ICGs, using MIC technology as a departure point. Among them were Renaissance Technologies, Inc, Newtown, Pennsylvania, and Drexel University of Philadelphia, who jointly developed the IQ System. The system provides a simple, repeatable non-invasive way of assessing cardiac function at dramatically reduced cost. The IQ System is in wide use in hospital intensive care units, emergency rooms, operating rooms, and laboratories in the U.S. and IQ has two basic elements: the non-invasive, disposable patient interface known as IQ-Connect and the touch screen monitor, which calculates and displays cardiac output values and trends. The hardware design of the original MIC was retained but IQ has advanced automated software that features the signal processing technology known as TFD(Time Frequency Distribution). TFD provides three-dimensional distribution of the hemodynamic signals being measured, enabling visualization of the changes in power, frequency, and time. This clinically proven capability allows IQ to measure all cardiac events without using estimation techniques required in some earlier systems.( Courtesy of National Aeronautics and Space Administration. The IQ-Connect interface electronically measures impedance changes across the thorax to reflect heart function. (Photo courtesy of National Aeronautics and Space Administration. e 2000 by CRC Press LLC
© 2000 by CRC Press LLC CARDIAC MONITOR he basic method of assessing heart function is thermodilution, a procedure that involves insertion of a catheter into the pulmonary artery and is demanding in terms of cost, equipment, and skilled personnel time. For monitoring astronauts in flight, NASA needed a system that was non-invasive and considerably less complex. In 1965, Johnson Space Center contracted with the University of Minnesota to explore the then-known but little-developed concept of impedance cardiography (ICG) as a means of astronaut monitoring. A five-year program led to the development of the Minnesota Impedance Cardiograph (MIC), an electronic system for measuring impedance changes across the thorax that would be reflective of cardiac function and blood flow from the heart’s left ventricle into the aorta. ICG clearly had broad potential for hospital applications but further development and refinement was needed. A number of research institutions and medical equipment companies launched development of their own ICGs, using MIC technology as a departure point. Among them were Renaissance Technologies, Inc., Newtown, Pennsylvania, and Drexel University of Philadelphia, who jointly developed the IQ System. The system provides a simple, repeatable, non-invasive way of assessing cardiac function at dramatically reduced cost. The IQ System is in wide use in hospital intensive care units, emergency rooms, operating rooms, and laboratories in the U.S. and abroad. IQ has two basic elements: the non-invasive, disposable patient interface known as IQ-Connect and the touch screen monitor, which calculates and displays cardiac output values and trends. The hardware design of the original MIC was retained but IQ has advanced automated software that features the signal processing technology known as TFD (Time Frequency Distribution). TFD provides three-dimensional distribution of the hemodynamic signals being measured, enabling visualization of the changes in power, frequency, and time. This clinically proven capability allows IQ to measure all cardiac events without using estimation techniques required in some earlier systems. (Courtesy of National Aeronautics and Space Administration.) The IQ-Connect interface electronically measures impedance changes across the thorax to reflect heart function. (Photo courtesy of National Aeronautics and Space Administration.) T
TABLE 114.1 Classification of TABLE 114.2 Physical Variables Sensed by Biomedical Sensors According Biomedical Sensors to Their Interface with the Host lacement, velocity, acceleration(linear and angular erature Noninvasive Noncontacting (weight and m nvasive Implanted gy(optical) involve some tissue damage associated with their installation. For example, a needle electrode for picking up electromyographic signals directly from muscles; a blood pressure sensor placed in an artery, vein, or the heart itself; or a blood flow transducer positioned on a major artery are all examples of invasive sensors. We can also classify sensors in terms of the quantities that they measure. Physical sensors are used neasuring physical quantities such as displacement, pressure, and flow, while chemical sensors are used to determine the concentration of chemical substances within the host. A subgroup of the chemical sensors that re concerned with sensing the presence and the concentration of biochemical materials in the host are known as bioanalytical sensors, or sometimes they are referred to as biosensors In the following paragraphs we will look at each type of sensor and present so ome of the important issues surrounding these types of sensors. 114.2 Physical Sensors Physical variables associated with biomedical systems are measured by a group of sensors known as physical sensors. A list of typical variables that are frequently measured by these devices is given in Table 114.2. These quantities are similar to physical quantities measured by sensors for nonbiomedical applications, and the devices used for biomedical and nonbiomedical sensing are, therefore, quite similar. There are, however, two principal exceptions: pressure and flow sensors The measurement of blood pressure and blood flow in humans and other animals remains a difficult problem in biomedical sensing. Direct blood pressure measurement refers to evaluation of the blood pressure using a ensor that is in contact with the blood being measured or contacts it through an intermediate fluid such as physiologic saline solution. Direct blood pressure sensors are invasive. Indirect blood pressure measurement involves a sensor that does not actually contact the blood. The most familiar indirect blood pressure measure- ment is the sphygmomanometer cuff that is usually used in most medical examinations. It is a noninvasive instrument. Until recently, the primary sensor used for direct blood pressure measurement was the unbonded strain gauge pressure transducer shown in Fig. 114.1. The basic principle of this device is that a differential pressure seen across a diaphragm will cause that diaphragm to deflect. This deflection is then measured by a displacement transducer In the unbonded strain gauge sensor a closed chamber is covered by a flexible diaphragm. This diaphragm is attached to a structure that has four fine gauge wires drawn between it and the chamber walls. a dome with the appropriate hardware for coupling to a pressure source covers the diaphragm on the side opposite the chamber such that when the pressure in the dome exceeds the pressure in the chamber, the diaphragm is deflected into the chamber. This causes two of the fine wires to stretch by a small amount while the other two wires contract by the same amount. The electrical resistance of the wires that are stretched increases while that of the wires that contract decreases. By connecting these wires, or more correctly these unbonded strain gauges, into a Wheatstone bridge circuit, a voltage proportional to the deflection of the diaphragm can be obtained In recent years semiconductor technology has been applied to the design of pressure transducers. Silicon strain gauges that are much more sensitive than their wire counterparts are formed on a silicon chip, and micromachining technology is used to form this portion of the chip into a diaphragm with the strain gauges integrated into its surface. This structure is then incorporated into a plastic housing and dome assembly. The entire sensor can be fabricated and sold inexpensively so that disposable, single-use devices can be made. These e 2000 by CRC Press LLC
© 2000 by CRC Press LLC involve some tissue damage associated with their installation. For example, a needle electrode for picking up electromyographic signals directly from muscles; a blood pressure sensor placed in an artery, vein, or the heart itself; or a blood flow transducer positioned on a major artery are all examples of invasive sensors. We can also classify sensors in terms of the quantities that they measure. Physical sensors are used in measuring physical quantities such as displacement, pressure, and flow, while chemical sensors are used to determine the concentration of chemical substances within the host. A subgroup of the chemical sensors that are concerned with sensing the presence and the concentration of biochemical materials in the host are known as bioanalytical sensors, or sometimes they are referred to as biosensors. In the following paragraphs we will look at each type of sensor and present some examples as well as describe some of the important issues surrounding these types of sensors. 114.2 Physical Sensors Physical variables associated with biomedical systems are measured by a group of sensors known as physical sensors. A list of typical variables that are frequently measured by these devices is given in Table 114.2. These quantities are similar to physical quantities measured by sensors for nonbiomedical applications, and the devices used for biomedical and nonbiomedical sensing are, therefore, quite similar. There are, however, two principal exceptions: pressure and flow sensors. The measurement of blood pressure and blood flow in humans and other animals remains a difficult problem in biomedical sensing. Direct blood pressure measurement refers to evaluation of the blood pressure using a sensor that is in contact with the blood being measured or contacts it through an intermediate fluid such as a physiologic saline solution. Direct blood pressure sensors are invasive. Indirect blood pressure measurement involves a sensor that does not actually contact the blood. The most familiar indirect blood pressure measurement is the sphygmomanometer cuff that is usually used in most medical examinations. It is a noninvasive instrument. Until recently, the primary sensor used for direct blood pressure measurement was the unbonded strain gauge pressure transducer shown in Fig. 114.1. The basic principle of this device is that a differential pressure seen across a diaphragm will cause that diaphragm to deflect. This deflection is then measured by a displacement transducer. In the unbonded strain gauge sensor a closed chamber is covered by a flexible diaphragm. This diaphragm is attached to a structure that has four fine gauge wires drawn between it and the chamber walls. A dome with the appropriate hardware for coupling to a pressure source covers the diaphragm on the side opposite the chamber such that when the pressure in the dome exceeds the pressure in the chamber, the diaphragm is deflected into the chamber. This causes two of the fine wires to stretch by a small amount while the other two wires contract by the same amount. The electrical resistance of the wires that are stretched increases while that of the wires that contract decreases. By connecting these wires, or more correctly these unbonded strain gauges, into a Wheatstone bridge circuit, a voltage proportional to the deflection of the diaphragm can be obtained. In recent years semiconductor technology has been applied to the design of pressure transducers. Silicon strain gauges that are much more sensitive than their wire counterparts are formed on a silicon chip, and micromachining technology is used to form this portion of the chip into a diaphragm with the strain gauges integrated into its surface. This structure is then incorporated into a plastic housing and dome assembly. The entire sensor can be fabricated and sold inexpensively so that disposable, single-use devices can be made. These TABLE 114.1 Classification of Biomedical Sensors According to Their Interface with the Biologic Host Noninvasive Noncontacting Body surface Invasive Indwelling Implanted TABLE 114.2 Physical Variables Sensed by Biomedical Sensors Displacement, velocity, acceleration (linear and angular) Temperature Force (weight and mass) Pressure Flow Radiant energy (optical)
PreSSUre PORT UNBONDED STRAIN GAUGES FIGURE 114.1 An unbonded strain gauge pressure transducer. have the advantage that they are only used on one patient and they do not have to be cleaned and sterilized etween patients. By using them on only one patient, the risk of transmitting blood-borne infections is eliminated In biomedical applications pressure is generally referenced to atmospheric pressure. Therefore, the pressure in the chamber of the pressure transducer must be maintained at atmospheric pressure. This is done by means of a vent in the chamber wall or a fine bore, flexible capillary tube that couples the chamber to the atmosphere This tube is usually included in the electrical cable connecting the pressure transducer to the external instru mentation such that the tube is open to the atmosphere at the cable connecter In using this sensor to measure blood pressure the dome is coupled to a flexible plastic tube, and the dome and tube are filled with a physiological saline solution. As described by Pascals Law, the pressure in the dome, and hence against the diaphragm, will be the same as that at the tip of the tube provided the tip of the tube at the same horizontal level as the dome. Thus by threading the tube into a blood vessel, an invasive procedure, the blood pressure in that vessel can be transmitted to the dome and hence the diaphragm of the pressure transducer. The pressure transducer will, therefore, sense the pressure in the vessel. This technique is known as external direct blood pressure measurement, and the flexible plastic tube that enters the blood vessel is known catheter. It is important to remember that the horizontal level of the blood pressure transducer dome must be the same as that of the tip of the catheter in the blood vessel to accurately measure the pressure in that vessel without adding an error due to the hydrostatic pressure in the catheter In addition to problems due to hydrostatic pressure differ- DIAPHRAGM ences between the chamber and the dome, catheters introduce pressure errors as a result of the dynamic properties of L (Se EAD WIRES catheter, fluid, dome, and diaphragm. These properties as well bubbles in the catheter, or obstructions due to clotted CATHETER WALL blood or other materials, introduce resonances and damping. These problems can be minimized by utilizing miniature pressure transducers fabricated using microelectronic semi- SEMICONDUCTOR STRAIN GAUGES conductor technology that are located at the tip of a catheter FIGURE 114.2 A catheter tip pressure transducer rather than at the end that is external to the body. A general are integrated into the diaphragm of the transducer such that they detect very small deflections of this arrangement for such a pressure transducer is shown in Fig. 114.2. As with the disposable sensors, strain gaug phragm. Because of the small size, small diaphragm displacement, and lack of a catheter with a fluid column, these sensors have a much broader frequency response, give a clearer signal, and do not have any hydrostatic "It must be pointed out that the use of such a sensor is not limited to blood pressure measurement. The strain gauge pressure sensor can be used to measure the pressure of any fluid to which it is appropriately coupled e 2000 by CRC Press LLC
© 2000 by CRC Press LLC have the advantage that they are only used on one patient and they do not have to be cleaned and sterilized between patients. By using them on only one patient, the risk of transmitting blood-borne infections is eliminated. In biomedical applications pressure is generally referenced to atmospheric pressure. Therefore, the pressure in the chamber of the pressure transducer must be maintained at atmospheric pressure. This is done by means of a vent in the chamber wall or a fine bore, flexible capillary tube that couples the chamber to the atmosphere. This tube is usually included in the electrical cable connecting the pressure transducer to the external instrumentation such that the tube is open to the atmosphere at the cable connecter. In using this sensor to measure blood pressure the dome is coupled to a flexible plastic tube, and the dome and tube are filled with a physiological saline solution.1 As described by Pascal’s Law, the pressure in the dome, and hence against the diaphragm, will be the same as that at the tip of the tube provided the tip of the tube is at the same horizontal level as the dome. Thus by threading the tube into a blood vessel, an invasive procedure, the blood pressure in that vessel can be transmitted to the dome and hence the diaphragm of the pressure transducer. The pressure transducer will, therefore, sense the pressure in the vessel. This technique is known as external direct blood pressure measurement, and the flexible plastic tube that enters the blood vessel is known as a catheter. It is important to remember that the horizontal level of the blood pressure transducer dome must be the same as that of the tip of the catheter in the blood vessel to accurately measure the pressure in that vessel without adding an error due to the hydrostatic pressure in the catheter. In addition to problems due to hydrostatic pressure differences between the chamber and the dome, catheters introduce pressure errors as a result of the dynamic properties of the catheter, fluid, dome, and diaphragm. These properties as well as air bubbles in the catheter, or obstructions due to clotted blood or other materials, introduce resonances and damping. These problems can be minimized by utilizing miniature pressure transducers fabricated using microelectronic semiconductor technology that are located at the tip of a catheter rather than at the end that is external to the body. A general arrangement for such a pressure transducer is shown in Fig. 114.2. As with the disposable sensors, strain gauges are integrated into the diaphragm of the transducer such that they detect very small deflections of this diaphragm. Because of the small size, small diaphragm displacement, and lack of a catheter with a fluid column, these sensors have a much broader frequency response, give a clearer signal, and do not have any hydrostatic pressure error. 1 It must be pointed out that the use of such a sensor is not limited to blood pressure measurement. The strain gauge pressure sensor can be used to measure the pressure of any fluid to which it is appropriately coupled. FIGURE 114.1 An unbonded strain gauge pressure transducer. FIGURE 114.2 A catheter tip pressure transducer