The shape of a eukaryotic cell or tissue is determined by the actions of the dynamic cytoskeleton pulling or pushing on the ECM or neighboring cells through a set of complex functions. In the previous chapters, we have considered the important elements of cytoskeletal filament dynamics and myosin activation as well as how cell–matrix and cell–cell interactions might affect the cytoskeleton. However, these motile systems must be orchestrated spatially and temporally to produce the correct types of motility for the needed functions of individual cells or of cells in tissues. Because of the dramatic differences in the behavior of individual cells and cells in tissues, we will discuss each type of behavior separately, making this a two-part chapter. In the first part, we will describe individual cell migration and motility, whereas in the second part, we will consider the cooperative processes that occur in tissue formation and remodeling. In both cases, the actin cytoskeleton is dynamic and the major active forces are generated by myosin II. However, there is a different organization of motile functions through the activation of different sites of actin polymerization and myosin activation in the different motile processes. At the individual cell level, we will consider the mechanisms of the few characterized types of motility and how the different elements of the cytoskeleton might be coordinated to produce migration or matrix remodeling. In tissues, the types of motility are dramatically different and the subcellular forces are difficult to measure. Thus, there is a lot of speculation, but some important principles such as the cohesion of the cells in the tissue have emerged. Modeling of the motility processes has started and such models will be very useful in prioritizing experiments to focus on the critical elements that will control each type of motility selectively. The goal in this area is to define the steps in motile functions, how they are coordinated as well as altered by forces or mechanics, and the roles of specific molecules involved.

Cell and tissue shape is critical for the survival of the organism. Because eukaryotic cells form without an exoskeleton, organism structure and shape must be developed using the tools that we have discussed in previous chapters; namely, the cytoskeleton, motor proteins, and extracellular matrices.

Although the blueprint for the body is built into the DNA sequence, it is still mysterious how a single fertilized egg cell develops into the mature organism. In mammals, the microenvironment of cells is critical for their proper differentiation. This comes from the simple fact that killing cells in a tissue will not seriously alter the development of that tissue, i.e. neighboring cells rapidly fill the gaps both physically and functionally. In other words, the plan for differentiation of the cell is not cell-autonomous but comes from dynamic interactions of the cell with its neighboring cells and matrix. As the single cell becomes a multicellular structure, there are a number of very standard changes in shape that take place. These involve a dynamic mechanical feedback between individual cells and the surrounding tissue. At a protein level, stem cells express many different proteins, which allow them to respond to many different stimuli, and define their differentiation program accordingly. These stimuli will be received from the microenvironment as well as circulating hormones, and will activate a specific set of complex functions that allow the cell to progress to the next step in development. At later times the microenvironment provides mechanical as well as biochemical signals, making it very difficult to take cells out of the embryo and expect them to differentiate properly. Furthermore, mechanical changes in the tissue are critical for proper development, and can only occur through dynamic feedback between the cells, and an ill-defined organ shape parameter. There are a variety of tyrosine kinases that when mutated or deleted will cause major changes in the shape of an organ. Recent findings indicate that many tyrosine kinases are directly linked to mechanosensing, which can explain how they have been genetically linked to the pathways that define shape. As cells differentiate into one of the over 300 different cell types, the set of proteins that are expressed becomes limited. Further, there are major epigenetic changes in nuclei that involve the modification of chromatin to silence genes that are not needed for the specific cell type. Generally, the regularly transcribed genes will not be silenced, whereas those that are not expressed become silenced in heterochromatin. We will discuss how the differentiation process is controlled and how differentiation is manifested both at the cellular and nuclear level.

In the design of a robust device, it is common to specify all of the ancillary functions needed, and then determine how they interface with other functions in the physical device. The previous chapter discussed how to analyze a complex function in the cellular context by controlling cell phases, so that one can reproducibly analyze the same function in a known cellular context. In the design of a robust device, the designer determines what is needed; however, if the device (cell) was developed over many generations through robust selection processes, many ancillary functions or features may be hidden. The treatment of biological systems as robust devices should include an appreciation for all of the needed functions, the necessary links between them and the dependent parameters, such as ATP, which contribute to larger cellular activity. This complete treatment of the problem can enable one to analyze biological functions with a new perspective. The major difficulty in this approach is that we do not appreciate the complexity of most biological systems in that dietary changes, exercise levels, startle reflexes, and environmental factors such as temperature, bacteria, or viruses can all alter the normal balance of cellular homeostasis. In many of these cases, the organism has compensatory or adaptive mechanisms to minimize the trauma of an abrupt environmental change. This is part of the definition of a robust device. In this chapter, we will discuss how to dissect a primary function into a series of dependent functions and their governing parameters. Although many of those parameters are automatically controlled in cells, knowing that they are important may help to explain why certain perturbations cause unexpected changes in a given function.

‘Systems Biology’ has been defined as the study of how interactions between specific components of biological systems give rise to that system's function and behavior. For example, the proteins and the cell phase in clathrin-mediated endocytosis. Operationally, many have approached these questions by using protein expression, and interactomics data to generate models with a number of experimentally determined reaction constants. The problem that occurs in many cases is that the system is too poorly constrained and therefore the models are built with too many adjustable parameters. A rule of thumb in mathematical modelling is that you can model the shape of an elephant with four adjustable parameters and get it to walk with a fifth.

The generation of force and the active transport of material over long distances are processes that are important in a number of complex functions. Both force generation and transport are driven by molecular motors that utilize the energy derived from ATP hydrolysis to move along polar filaments of the cytoskeleton. This movement generates the forces needed for synthesis, packaging, and transport of cellular components, and enables the cell to do work and maintain tension in tissues. The best-understood motor proteins are myosin and kinesin, which move on actin filaments and microtubules, respectively. Other motor proteins that move on DNA, on RNA, and on the protein backbones have roles in synthesis, packaging, and degradation processes. In a broad view, molecular motors couple the Brownian movements of proteins (vibrational, rotational, or translational) to the dissipation of energy (from ATP or GTP hydrolysis, or from coupling to a proton gradient). The three major types of motors, myosin, kinesin, and AAA superfamily of ATPases, are significantly different in their designs and functions. Although single-molecule studies have provided many insights into the mechanisms of motor protein function, the rules that control their motility are not well understood. The mechanisms that regulate motor protein activity are complex yet highly important because the level of force and/or displacement that is generated must be tightly controlled in order for the complex functions to be carried out properly (for more background on motors, see Howard, 2000).

Motor protein complexes constitute a major class of proteins that are needed for many functions, as outlined in the textbox above. Analyses of the genetics of motor proteins have been somewhat frustrating because knocking out individual motor proteins often produces ‘unremarkable’ phenotypes. For example, individual myosin I motor proteins, which represent a diverse group of single-headed motor proteins, can be knocked out in the amoeboid cells of Dictyostelium discoideum, with little effect. Only when several myosin I proteins are knocked out do cells show significant changes in function. In the early days of protein knockouts, this result was viewed by many as an indication that the myosin I proteins were unimportant and young faculty were discouraged from working on them because it would be doubly hard to get tenure.

Despite a lack of exoskeleton, isolated animal cells normally exhibit stable, nonspherical shapes with excess membrane area. To maintain cell shape, the plasma membrane conforms to a cytoskeleton located inside the cell, but the membrane surface area to cell volume ratio determines how extensively the membrane can conform. In a few cases, such as endothelial cells in capillary tubes, the cytoskeleton alone can support the cell shape. In most cases, however, the cytoskeleton is dynamic, and defines the cell shape in concert with the cell volume, and the effect of contracting against external contacts, or adhesions. Modulation of these adhesions, whether they are between adjacent cells, or cells and matrices, provide the stimuli to initiate cytoskeleton dynamics. These dynamics, which include filament assembly and disassembly, typically determine any changes in the shape of the cell. Actin filaments are often assembled from adhesion sites or sites of membrane extension, both of which lie primarily at the cell periphery. They are then pulled inward and disassemble in a process known as ‘actin treadmilling.’ Actin filaments are contracted by myosin and this creates tension in the cytoskeleton and is responsible for tissue organization and the cohesive property of cells. Paradoxically, the rapid loss of contractile force increases filament dynamics, and cytoskeleton assembly. Cohesion of cells over longer periods is stabilized by intermediate filaments. These appear to be the safety net that prevents acute fracture of cells in epithelia under tension. Microtubules, on the other hand, help stabilize and define cell polarity and structure. Microtubules originate from the microtubule-organizing center (MTOC) and provide directional pathways on which motors will transport membranous organelles and other cellular components. During mitosis, the dynamic microtubules of the mitotic spindle play critical roles in the transport of chromosomes to the daughter cells. Thus, the cytoskeleton is a dynamic, mechanically active component of the cell that is responsible for shaping the cell and its environment as well as for organizing the intracellular organelles.

The cytoskeleton is comprised of three long filament systems; specifically, microtubules, actin filaments, and intermediate filaments. These filaments are crosslinked by motor proteins or multivalent binding proteins, which serve to stabilize the cytoskeleton, and provide it with dynamic qualities including the ability to disassemble, reassemble, and contract. As evidenced by photobleaching recovery experiments, filament subunit exchange occurs on the timescale of minutes for actin and microtubules.

Cellular functions have evolved over time to better enable organisms to survive major environmental challenges (see Chapter 1). Improvements to basic functions or new functions that more successfully supported survival were preserved and shared between organisms, either by infections or by interbreeding. Because the environment is constantly changing, the complex functions have evolved to be robust so that they will work under many different conditions and the design principles of robust devices (see text box below) can be used to understand them. A complex function involves multiple functional modules coordinated to perform a complex task. In this chapter, we will describe a general approach to understanding the features of complex functions and how the functional modules that underlie complex functions may be linked to yield the desired emergent properties across different scales. An emergent property is the outcome of many steps and many modules in a complex function. We suggest that models of complex functions violating the principles of robust devices are likely to be wrong. Furthermore, we will describe why it is important to quantitatively measure the performance of complex biological functions (outputs) under different circumstances (inputs) to better test models of different complex functions.

Principles of Robust Machines with Standard Functions

We propose that cells are highly engineered, robust machines. They are also very small machines where all actions are dominated by diffusion. The stochastic nature of diffusion processes can account for some of the observed biological variability. However, biological systems have devised mechanisms to use diffusion to drive muscle movements and to direct the shaping of the organism. Evolutionary refinements of the basic mechanisms of biological systems enable them to reproducibly create organisms of diverse shapes using the information encoded in the DNA. Thus, fruit flies with the same DNA will look the same as well as identical twins. In the case of the twins the development took many years and yet they often do look identical. Thus, the robustness of the biological systems extends to making reliable decisions using inherently noisy stochastic processes. Because it seems that the cells that form the basis of biological systems are robust machines, the complex functions that they utilize should follow the design principles of robust devices (Figure 2.1, from Thomas et al., 2004).

This book is designed to introduce the reader to the fundamental information necessary for work in the clinical setting, supporting the technology used in patient care. Beginning technicians/ technologists can use this book to develop a working vocabulary and fundamental knowledge of the Healthcare Technology Management (HTM) profession. Content includes a wide variety of medical technology, with an emphasis on device types and classifications; individual manufacturers are utilized as examples.

This work is intended for the reader with a fundamental understanding of anatomy, physiology, and medical terminology appropriate for their role in the healthcare field, and assumes the reader's understanding of electronic concepts, including voltage, current, resistance, impedance, analog and digital signals, and sensors. The material covered in this book will assist the reader in the development of his or her role as a knowledgeable and effective member of the patient care team. The second edition features revisions to all of the content to reflect changes in healthcare, regulations, standards, and technology. A new chapter addresses device testing, with emphasis on safety inspections. A second new chapter explores the interface of medical technology with the electronic medical record.

A vital connection exists between technology and the care of patients. In many cases, healthcare workers depend on technology to administer care or treatment or to make a diagnosis. This book helps readers understand how technology is tightly woven into patient care. The role of technical support for the medical team is, therefore, essential in the delivery of effective medical care.

The section of each chapter entitled “For Further Exploration” encourages readers to use the Internet to obtain in- depth information about a related topic. The questions are designed to push the reader to integrate concepts and ideas using external sources. Answers to the questions are not specifically available within the chapters. Research exercises encourage one of the most important professional skills – the ability to investigate topics that are not well understood. In the clinical setting, it is virtually impossible to be an expert about all technology and aspects of patient care. The ability to effectively search for information is vital.

Introduction

Technology is used to support heart function in numerous ways. Perhaps the most common and well- known device is the defi- brillator. In addition, the amazing life- saving powers of artificial hearts and implantable devices regularly capture the attention of the public and news media.

ACLS (advanced cardiac life support) is a detailed protocol to provide life- saving cardiac care. HTM professionals may be involved in the selection of technology and technical protocols used in a crisis. In addition, technicians may help establish training programs and awareness of the medical devices involved in emergency response.

Defibrillators

A defibrillator is familiar to most only from life- saving moments on television medical shows, but is often used in real life as first responders seek to help those with medical emergencies. It is a fairly simple device that delivers a large amount of energy across a patient's chest when the heart is not beating properly: that is, when the pacemaker of the heart, the sinoatrial (SA) node is not properly generating a periodic waveform. When the heart is not beating with a pattern, all cells are contracting at different times, this is known as fibrillation. Defibrillators, or defibs (as they are often called) in use today send about 3,000 volts (V) – up to 20 amperes (A) – across a patient's chest. (Note: The amount of voltage and current vary tremendously based on the patient's size and therapeutic settings.) This large amount of energy causes all cells in the heart to depolarize at once. This action may allow the SA node to resume function and generate a normal electrical pattern. Sometimes the SA node can recover and resume electrical control of the heart, but sometimes it cannot. The shape of the energy waveform delivered by a defibrillator has evolved with experience. The Lown waveform was the therapeutic waveform standard until recently. It looks like a damped sine wave.

The biphasic waveform is the standard of care in defibrillators today. It has both a positive and negative component and produces much better results for patients more quickly. Because it better simulates the electrical conduction pattern through the heart, biphasic waveforms are able to deliver results with less energy. The waveform is approximated in Figure 8.1.

Introduction

As part of the healthcare team, technicians must ensure medical technology is safe and available when needed by clinicians. In the healthcare workplace, work is done to ensure a device is operating properly. This is in contrast to corrective actions designed to remedy problems as a result of a device malfunction. The kind of work described in this chapter is focused on reducing equipment failures and discovering hidden problems before they could impact patient care or device performance.

Clinical sites and administrators generally define the scope of medical equipment managed by HTM technicians. As discussed in Chapter 2, medical technology is often grouped into three broad categories: therapeutic, monitoring, or diagnostic. Variation among hospitals is common based on historical support or individual skill sets, although devices that are disposable or singleuse and most implantable devices are beyond the responsibility of the HTM technician.

Before any work begins on any medical device, technicians should be sure to utilize appropriate personal safety measures as discussed in Chapter 5.

Device Inspection

When a new device is delivered to an institution, removal from the packing materials, initial assembly, and incoming inspection is performed. The complexity and time required to complete these steps varies greatly depending on the device. As mentioned in Chapter 1, incoming inspections are an essential part of the HTM technician's workload, with efforts focused on the assurance that a new device will function properly when put into service within the healthcare setting.

Preventative maintenance, another important workplace responsibility, evaluates the performance of an existing device to ensure proper operation. These activities are typically scheduled utilizing a predetermined timeline (such as once per year). The goal of these actions is to identify undetected problems before they impact patient care, reducing equipment downtime and reducing overall hospital costs.

Simple visual inspections look for signs of deterioration, damage, or missing hardware. The stressful clinical environment may result in unintended equipment mishandling that can cause broken plastic parts, missing doors or knobs, frayed power cords, or gashes. Power cord damage, especially at the junction with the device, can be both common and potentially hazardous. Experience in healthcare settings will offer technicians the opportunity to see a wide variety of device damage (some surprising and inexplicable), and to develop a special sense to predict and find device deterioration.

Introduction

The use of technology to push fluids into the circulatory system of a patient has evolved and expanded over time. In the past, glass bottles of fluids utilized gravity to promote fluid flow to “drip” fluids into a patient. As technology expanded into healthcare, the bottles were replaced with plastic bags and gravity was no longer medically adequate. Electromechanical pumps are more reliable and provide constant monitoring of fluid delivery. In addition, the flexibility of some pumps has improved medication dosing and caloric delivery. Healthcare has come to depend on the use of technology to deliver fluids and medications to patients.

Infusion Pumps

One of the most common pieces of equipment in the hospital, the infusion pump (also called intravenous pump, IVAC, and IV pump) delivers medication, blood, or fluid into the patient over a specific period of time at a particular rate. The name used may reflect brand names from the past, including IVAC. Many patients will be connected to several pumps delivering fluids to the patient through a vein (hence, the term “intravenous”). The pump ensures an accurate rate and, therefore, an exact dose. In addition, should there be a problem with the fluid delivery, an occlusion (blockage of the tubing) perhaps, or the complete fluid amount has been delivered, an alarm will sound to alert staff. The electronic monitoring allows delivery of IV fluids with minimum human intervention.

Bags, filled with fluids of many kinds, are hung on poles, connected through tubing to the pump, and then through the pump to the veins of the patient. Settings on the device include delivery/ flow rate as well as alarms to indicate blockages or empty fluid bags.

There are different techniques employed to pump in the fluid. One of the most common is a peristaltic pump. Rollers (in most cases) squeeze the tubing to push in the fluid. Traditional tubing from the fluid- filled bag to the patient is used.

Another method requires some additional disposable cassettes that hold the liquid for a piston to push the liquid. This requires that the infusion tubing be specifically chosen to work with the type of pump the hospital owns.

A significant reason for death and long-term disability due to head injuries and pathologic conditions is an elevation in the intracranial pressure (ICP) due to vascular compromise and secondary sequelae causing edema. ICP measurements before and after injury in a completely closed-head environment have a significant research value, particularly in the acute postinjury period. With current technology, a tethered fiberoptic probe penetrates the brain and therefore can only remain implanted for relatively short time periods. Use of the probe also can cause complications such as infection and hemorrhage and prohibit immediate (at the time of injury) and long-term measurements of ICP. A small, fully embedded, wireless ICP device may simplify clinical management and research protocols by offering a means for semi-invasive and long-term ICP measurement following brain injury. In this chapter, a new digital wireless ICP (DICP) device is described. The dynamic ICP measurement performances of both the analog ICP (AICP) devices (described in Chapter 2) and the DICP devices are evaluated in a specific traumatic brain injury (TBI) (swine) model of closed-head rotational injury.

Introduction

In Chapter 2, a prototype of an AICP device operating in the industrial-scientific-medical (ISM) band at 2.4 GHz was described that successfully simplified the surgical procedure by reducing the infection rate, the risk of hemorrhage, and the degree of tissue injury.

The AICP device was implanted in a canine model only for a static test, and hypo- and hyperventilation were used to affect variations in ICP. Dynamic ICP variations as a result of TBI in a completely closed-head environment are of paramount importance for understanding the development of a prolonged postconcussion syndrome and facilitating institution of the correct treatment at different stages, particularly in the acute postinjury period. Currently, in experimental (animal) models of TBI, a tethered fiberoptic probe (if inserted before the injury) has to be removed before an injury is induced in order to avoid significant focal damage at the point of probe insertion. Moreover, reinsertion of the probe is possible only after the animal's vital signs have stabilized. However, the act of breaching the cranium after the injury affects the fidelity of the ICP measurements. In addition, proposed noninvasive ICP (NICP) solutions, such as the pulsatility index method based on the use of trancranial Doppler, argued by Figaji et al. [1], have been shown to be insufficient for accurate ICP estimation.

Introduction

Doppler radar has recently been extensively used in noncontact cardiopulmonary monitoring [1–3]. A continuous wave (CW) microwave signal is transmitted toward a human subject. Physical motion caused by the respiration and heartbeat of the human subject phase modulates the transmitted signal and reflects it back to the transmit antenna, where it is received and phase demodulated to yield the heart and respiration rates of the subject. Physical motion of the human chest during respiration and heart motion are measured to be about 0.2 to 2 and 8 to 20 mm, respectively [4]. Thus the system has to be very sensitive to phase changes, which are caused by path-length variations. For a stationary transmitter and subject, this path length only varies with a subject's heartbeat and respiration. A nonstationary transceiver antenna or a fidgeting subject will produce additional path variations causing interference in radar signal (Figure 7.1).

There are cases where the transmit/receive antenna cannot be assumed to be physically stationary. For example, if the transceiver is a handheld unit used in search and rescue operations or to sense through walls in military applications, “hand shake” of the operator will introduce path-length variations that phase modulate the received signal in addition to that of the target's cardiopulmonary motion. Also, if the antenna is placed on a platform subject to some vibration, the vibration can cause antenna motion, creating an interference with the radar signal. Monitoring a driver in a vehicle is an example of such an application. Thus the final demodulated signal will include components resulting from operator's unwanted hand shake to the extent that life signs monitoring will become impossible due to excessive interference. The fidgeting of the subject, which can be the result of coughing, sneezing, itching, and similar activities, is another source of this type of interference.

While most sources of unwanted interference motion are random, they can still be categorized to a certain extent by their frequency spectrum and amplitude. For example, a 2003 Ford Taurus with a V6 engine being driven on a flat freeway at a speed of 65 mph creates about 3 to 9 mm of shake at a low frequency of 1.2 Hz [5].

The problem of undesired instrument shake is similar in still image and video cameras, where it causes motion blur in the captured image.

Introduction

One limitation with Doppler radar is that for vital sign monitoring, any torso movement by the subject will affect the measurements. Other limitations include interference from moving objects or people in the vicinity and an inability to detect multiple targets. These issues arise due to the fact that a continuous-wave (CW) radar motion-detecting system is not inherently selective and will detect any motion in its field of view. Various solutions have been proposed for this, such as the use of multiple antennas with blind source separation (BSS) techniques to identify multiple respiration signatures [2,36] and use of two and four radars to cancel body sway [12,38]. BSS techniques are very effective in identifying multiple motion signatures but cannot associate those signatures with a particular source, leading to ambiguity in the interpretation of results. A good solution still does not exist for identification of a subject from the environmental clutter and making the Doppler radar system selective.

Bringing selectivity to the radar implies introducing ways to ensure that the motion signals obtained correspond to the desired source. By rejecting clutter motion and detecting the physiologic motion of a subject, we are implementing the first stage of selectivity. The only way to resolve targets without placing any circuit on them is by spatial resolution and range. Spatial resolution can be brought to the radar through coherent detection using pulse Doppler radar. This principle is used in synthetic aperture radars (SARs) and inverse synthetic aperture radars (ISARs) [33]. In order to achieve good resolution, we would have to use millimeter-wave signals and associated circuitry and would still have ambiguities in the range. Spatial resolution can also be obtained through multiple-input, multiple-output (MIMO) systems and BSS techniques, but the sources of motion would still remain ambiguous. Range can also be calculated using frequency-modulated continuous-wave (FMCW) radars, but then Doppler processing would become more challenging. The resolution provided by FMCW radar is also limited by the bandwidth of frequencies used.

Introducing modulation at the source of motion may allow more flexible solutions compatible with the current Doppler radar system. The way to achieve selectivity would be to have some form of modulated backscatter from the subject and no modulated backscatter from other objects, similar to radiofrequency identification (RFID) systems. Although RFID technology is mature and easily available, it is difficult to apply to motion-sensing applications.

Introduction

The focus of this chapter is external human respiration. Moving air in and out of the lungs is external respiration and the focus of technological interventions. The exchange of gases in the alveoli is part of external respiration (although it occurs within the lungs) and reflects the effectiveness of breathing – note that internal respiration does not mean “inside the lungs,” it refers to the gas exchange at the cellular level within the tissues. Patients need to move air in and out of the lungs and exchange gases in the alveoli, a substructure of the lungs. Oxygen is taken in by the body and carbon dioxide is expelled. Air is made up of 79% nitrogen, 20.96% oxygen, and 0.04% carbon dioxide. However, the air that is expired out of the lungs contains differing percentages. Expired air still contains 79% nitrogen (unaffected by respiration), but notice that the concentration of oxygen is decreased to 17%, and the concentration of carbon dioxide is substantially increased to 4%.

Respiration Effectiveness

One important patient characteristic that is monitored is the effectiveness of respiration – a patient may be breathing (air moving in and out), but it is more important to know whether this activity is resulting in appropriate oxygenation of the body. One method to examine breathing effectiveness is to evaluate the properties of a patient blood sample. Chemical analysis of blood (often performed at the bedside or in the unit), especially the measurement of pH (i.e. the acidity of the blood), can help clinicians determine a patient's respiratory status. See Chapter 15 for more information regarding blood testing.

Pulse oximetry, as discussed in Chapter 7, is also used to simply and non- invasively characterize the effectiveness of respiration. The percentage of hemoglobin molecules that carry oxygen can be displayed by a simple device and will increase or decrease as the body is able to absorb and circulate oxygen.

Capnography is the measurement of carbon dioxide concentrations in expired air. This technique evaluates the changes in carbon dioxide values over time. Expired air is sampled or passed through sensors that can electronically detect the concentration of carbon dioxide. Sensors that utilize infrared (IR) light and light detectors are typically placed within the tubing that connects patients with respiratory devices.

Introduction

Interest in ultra-wideband (UWB) technology has increased significantly since the Federal Communications Commission's (FCC's) inquiry in 1998 and approval of its use in 2002. The FCC opened up two bands, the 3.1- to 10.6- and 22- to 29-GHz frequency bands. UWB has been used for both communication and radar applications. The fundamental purpose of this chapter is to open up new areas of application for UWB technologies applied to medicine. This includes pushing the achievable limits in terms of high-accuracy indoor three-dimensional (3D) localization using UWB technology and to use this technology in a real-time location system that tracks multiple tags simultaneously with high 3D accuracy in the millimeter range. The application of this technology goes beyond localization to other areas such as breast cancer detection, human gait analysis, and vital signs monitoring, and the list goes on.

Historically, Time Domain Corporation has pioneered real-time precise location of people and assets. Time Domain is the first company to unleash its full potential [1]. Their pulse-on system enables real-time localization in the most difficult environments – where GPS fails and where ad hoc or moving frames of reference are required. Multispectral Solutions, Inc., also used UWB for multiuser networking applications – more specifically, an ad hoc wireless UWB communications network for tactical voice and high-speed communications, a long-range UWB system for over-the-water and non-line-of-sight voice, data, and video communications, and a wireless UWB communications network for support of both tactical and strategic (long-haul) communications [2].

In this chapter, we will focus on three areas: (1) indoor positioning, (2) human gait analysis and vital signs detection, and (3) early breast cancer detection.

Overview of UWB Technology for Indoor Positioning Systems

It is important to recognize that the use of UWB technology in a high-performance localization system requiring millimeter 3D accuracy has not been well researched, and far fewer systems have been developed compared with its use in cheaper but more widespread systems with lower accuracy requirements on the order of 10- to 15-cm 3D accuracy.

These localization systems based on using UWB narrow pulses are typically comprised of a transmitter and numerous receivers. The transmitter (the tag) has a narrow-pulse generator (in the picosecond range) controlled by a clock, a power amplifier, and a wide-band omnidirectional antenna.

Introduction

The clinical laboratory is vital to a hospital's ability to treat patients. Bodily fluids from patients are analyzed for their chemical makeup as well as evidence of disease. Many therapeutic and treatment decisions are made based on the results of this important analysis. Almost all testing is automated and most devices perform many tasks. As a very equipment- intensive department, technical support is vital. The high level of complex equipment does require some hospitals to obtain service contracts for the support of clinical laboratory equipment.

Common fluids from patients analyzed include blood, urine, and cerebrospinal fluid. A tremendous number of categories and tests are performed. This chapter focuses on the principles that form the foundation for the complex equipment. Most devices utilize multiple reagents, bar codes, robotics, and computers to perform the sample preparation and multiple tests. In addition to automated fluid analysis, many laboratory tests evaluate tissue and fluid samples for evidence of abnormalities. Many of these tests are not automated and require the expertise of a pathologist or clinical laboratory technician.

The naming conventions associated with this part of healthcare have varied over time. Originally termed medical technology, a shift was made to more clearly identify the profession. Previously, clinical staff who managed sample analysis techniques were known as “med techs,” causing confusion with medical assistants, phlebotomists, and HTM technicians. Now laboratory staff are often called clinical laboratory scientists. Newer labels for the department include medical laboratory, clinical laboratory, and clinical technology.

Clinical laboratories have their own specific regulations, and organizations that offer guidelines and best practices. These include the American Association of Blood Banks (AABB), College of American Pathologists, and Clinical Laboratory Improvement Amendments (CLIA). CLIA observance is a federal requirement.

Blood Analysis

Many tests are performed on blood. A common test is blood cell count. The automation of this test was vital to improvement in analysis speed. W. H. Coulter created an automated method of particle counting using electrical impedance. As the blood cells pass between electrodes, the impedance increases in pulses. These pulses can be counted to determine the amount of cells (particles) in a sample. Since red blood cells and platelets have different sizes, the pulses vary in size. This allows for very specific results.