by Robert A. Freitas Jr.
© Copyright 1998, Robert A. Freitas Jr.
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The first volume of Nanomedicine describes the preliminary technical issues involved in medical nanodevice design, along with some details of the required foundational technical competencies. These required competencies include the ability to sort and transport molecules; chemical, acoustic, and other physical sensors; shape, texture, and compositional control of external surfaces; in vivo power storage, generation, and transmission; communication among nanorobots, and between doctors, patients, and in vivo nanorobots; navigation throughout the body and inside individual cells; manipulation and locomotion at the microscopic level; nanocomputation, timers and nanoclocks, cryothermal operations, and defensive cellular armaments.
Chapter 1 defines the field of nanomedicine and its objectives, keyed to the "biological existence proof" of the feasibility of nanotechnology. Several thought experiments are employed to help the reader develop an intuitive appreciation of time, space, and mechanics in the microworld, where nanorobots will be operating. The goals of biotechnology-based "molecular medicine" are carefully distinguished from the goals of nanomedicine. The evolution of the concept of nanomedicine and cell repair machines is described as the natural culmination of millennia of medical history. The limits of nanomedicine are presented, although by 20th century standards these limits appear, for the most part, quite tolerable and modest in scope. The applicability of the Hippocratic Oath in the nanomedical era is explored. The chapter finishes with an overview of the entire three volume series.
Since nanomachines cannot yet be built, it is necessary to credibly establish that such devices are feasible, and that their design, fabrication, and operation violate no laws of physics and will obey sound engineering principles. A number of classical objections to nanotechnology (e.g. quantum mechanics, thermal motions, friction) are considered and resolved. Precursor technologies to nanotechnology and nanomedicine, such as micromachines/MEMS, telemicrosurgery, and tissue engineering, are briefly reviewed. The concept of molecular manufacturing is reviewed, including the differences between top-down and bottom-up manufacturing. Three principal paths to molecular manufacturing — proximal probes, biotechnology, and supramolecular chemistry with self-assembly — are outlined, and a few alternative pathways are suggested. The chapter concludes with discussions and brief descriptions of molecular machine parts, nanocomponents, and nanomaterials, along with the results of molecular computational simulations; nano-assemblers and the Foresight Institute Feynman Prize; desktop manufacturing; and the challenges of molecular engineering and design (nano-CAD).
The human body is comprised of at least 100,000 different molecular species, including perhaps 5,000 different species within each tissue cell (Section 3.1). Transporting and sorting such a broad range of essential molecular species will be an important basic capability of many nanomedical systems.
The three principal methods for distinguishing and conveying molecules that are most useful in nanomedicine are diffusion transport (Section 3.2), membrane filtration (Section 3.3), and receptor-based transport (Section 3.4). The chapter ends with a brief discussion of binding site engineering (Section 3.5).
Medical nanorobots must be able to acquire information from their environment if they are to properly execute their assigned tasks. Such acquisition is achieved using onboard nanoscale sensors, or nanosensors, of various types. Nanosensors make it possible for medical nanodevices to monitor environmental states at three different operational levels: (1) internal nanorobot states, (2) local and global somatic states (inside the human body), and (3) extrasomatic states (sensory data originating outside the human body).
Specific nanosensor technologies include sensors to detect chemical, displacement and motion, force and mass, acoustic, thermal, and electromagnetic stimuli. Typical sensor device mass, volume, and maximum sensitivity limits are summarized in each Section. The chapter ends with a brief description of in vivo bioscanning and external macrosensing.
It has been asserted that nanomechanical systems fundamentally differ from systems of biological molecular machinery in their basic architecturespecifically, that nanomechanical components are supported and constrained by stiff housings, while biological components often can move freely with respect to one another. As regards medical nanodevices, this may be a somewhat artificial distinction. The likelihood that most nanoscale components will be connected in rigid arrays does not imply that the nano machines themselves must be entirely rigid in shape, nor does it rule out the possibility that some major nanomachine components may be designed to allow periodic reconfiguration and repositioning.
A flexible or "metamorphic" surface is a nanodevice exterior surface comprised of independently controllable elements that can translate or rotate their relative positions, thus enlarging or contracting total surface area of the device, or changing its shape, with or without altering the membership of elements in the surface, with or without altering the enclosed volume of the entire nanomachine, while maintaining continuous structural integrity and nonpermeability of the surface. The range of possible designs is enormous.
Device energetics may represent the most serious limitation in nanorobot design. Almost all medical nanodevices will be actively powered. Mechanical motions, pumping, chemical transformations and the like all require the expenditure of energy. Even a drug molecule interaction with a biological receptor site reduces free energy by ~50 kT. Heat dissipation is also a major consideration in nanomachine design, particularly when large numbers of nanomachines are deployed in cyto or in vivo.
Chapter 6 opens with a review of the various forms of stored energy that may be accessible to working nanodevices. Subsequent sections describe how various forms of energy (likely to be available in vivo) can be converted into many other formsincluding thermal, mechanical, acoustic, chemical, electromagnetic, and nuclear sourcesand how such energy may be transmitted from one place to another inside the human body. The chapter closes with an enumeration of issues and techniques useful in assessing energy requirements and performance restrictions in medical nanodevice design.
Communication is an important fundamental capability of medical nanorobots. At the most basic level, nanomachines must pass sensory and control data among internal subsystems to ensure stable and correct device operation. They must also exchange messages with biological cells, communicating with the human body at the molecular level. Nanodevices must be able to communicate with each other in order to: (1) coordinate complex, large-scale cooperative activities, (2) pass along relevant sensory, messaging, navigational, and other operational data, and (3) monitor collective task progress. Finally, nanorobots must be able to receive messages from, and transmit messages to, both the human patient and external entities including antennas and telecommunications links, laboratory or bedside computers, and attending medical personnel.
Chapter 7 opens with an analysis of the most common communication modalities and communication network architectures, followed by a discussion of the many specific communication tasks to be performed. This latter discussion, constituting about half of Chapter 7, concentrates on the following specific situations: Inmessaging from external sources, inmessaging from patient or user, intradevice messaging, interdevice messaging, biocellular messaging, outmessaging to the user, outmessaging to an external receiver, and transvenue outmessaging.
It is difficult to imagine any significant application of medical nanodevices which does not involve navigation, however crude. Devices intended to monitor somatic states, assemble artificial internal structures, remove tumors or foreign matter, combat infections, or perform repairs, must normally be extremely tissue- or cell-specific. Navigation is also required to execute many control protocols, to locate dedicated energy, communication, or navigational helper organs, or to stationkeep and coordinate with other nanodevices. Even bloodborne nanorobots intended to operate solely at the systemic levelsuch as nanobiotics, immunocytes, or respirocytes (artificial red cells)must know if they have been prematurely ejected from the vasculature so that they may cease functioning or at least modify their activities.
Chapter 8 opens with a broad survey of human somatography. This is followed by general discussions of positional navigation including high-resolution navigational networks; functional navigation, ranging from simple demarcation strategies to thermographic, barographic, and chemographic navigation, as well as continuous real-time biotagraphic mapping; and cytonavigation, including cytometrics, molecular cytoidentification, and navigational cytography and nucleography. The chapter concludes with a brief look at the challenges of ex vivo navigation.
Manipulation and mobility will be important basic capabilities in many classes of medical nanodevices. This chapter opens with a discussion of adhesion forces at the molecular level and the performance of nanoscale fluid pumps and fluidic circuits. Several classes of nanomanipulators are described, along with various tool tips and manipulator configurations such as massively parallel manipulator arrays. Techniques of in vivo locomotion are described in the context of bloodstream and nanodevice rheology, including swimming, anchoring, nanodiapedesis, cell penetration, intracellular mobility, and cytocarriage. The chapter concludes with a discussion of ex vivo locomotion.
Chapter 10 describes a number of important additional technical capabilities that may prove useful to some or all medical nanodevices, in various scenarios or theaters of operation. The most important of these capabilities is computation, including nanomechanical, nanoelectronic, and nanoscale data storage technologies. Other capabilities include timers and nanoclocks with long-term nanosecond stability; high-pressure materials storage; limitations and techniques of cryothermal operations; and defensive cellular armaments which will allow pathogenic cells to be efficiently dispatched.
The second volume of Nanomedicine considers the system-level technical requirements in the design and operation of medical nanodevices, and systems of such nanodevices.
Part 1 of Volume II describes aspects of nanomedical operations and configurations including issues of closed-loop sensory feedback and teleoperation, swarm control, centralized vs. distributed control architectures, repair and reliability issues, deployment configurations, medical utility fogs, and replicators.
Part 2 of Volume II deals with a multitude of issues involving clinical safety and performance, including medical nanorobot biocompatibility, immunoreactivity and thrombogenicity, methods of nanorobotic somatic ingress and egress, side effects of nanomedical treatments, nanodevice failure modes and unwanted environmental interactions, potential iatrogenic factors, and other safety issues.
Part 3 of Volume II reviews the various classes of medical nanosystems, including instruments and tools, diagnostic systems, specific medical nanorobot devices, chromatin and protein editors, and various complex nanorobotic systems including cell repair and personal defensive systems.
The third volume of Nanomedicine describes the full range of nanomedical applications using molecular nanotechnology inside the human body. It is written from the perspective of a future nanomedical physician or biomedical practitioner in an era of widely available nanomedicine.
Volume III describes appropriate nanomedical treatments for cardiovascular repair, disease processes, trauma and acute injuries including amputations and thermal/radiation burns, and brain and spinal injuries. Nanomedical issues in nutrition and digestion, sex and reproduction, and cosmetics and recreation are explored, along with proof-of-principle designs for numerous nanoengineered artificial organs and human augmentation systems. Chapter 30 describes the control and elimination of most aging processes and causes of death prevalent in the 20th century, the ultimate limits to human longevity, and current cryonics preservation strategies along with plausible revival protocols. The volume concludes with a discussion of possible social impacts and social acceptance of nanomedicine, nanotechnology implementation timelines, and some speculations on the future of hospitals, pharmaceutical companies, and the medical profession.
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