This chapter describes software construction and testing. These are the very concrete steps in the software life cycle (Section 14.1). Next, we discuss “construction,” or coding (Section 14.2), beginning with a brief review of key regulatory issues. We follow this with a presentation of programming topics and conclude this section with an extended discussion of risk management in the context of the programming process.

This chapter presents an overview of current medical software applications and the factors that promise to drive growth in this area. We begin this chapter by defining and discussing some important terms such as digital biomarkers and digital health (Section 7.1).

This chapter provides background on the constraints imposed on software by the need to operate within a healthcare environment. We first present an overview of the environment and the constraints under which our software must operate (Section 3.1).

This chapter describes the process of software validation. We first begin with a brief overview of what validation is. We then review the regulatory guidance for validation (Section 15.1) in general, and then provide an extended discussion on the issues that affect the validation of software modules that use artificial intelligence/machine learning (AI/ML) techniques in particular.

Trafficking of molecules both into and out of a cell is a normal activity necessary for cell survival. Cells have evolved elaborate strategies for these transport processes while ensuring the integrity of the cell membrane. Some of these transport processes are thermodynamically driven, whereas others involve active transport mechanisms. Nanomedical design attempts to use the naturally occurring transport mechanisms to bring drugs into single cells.

There are a number of features of nanomedicine that make it a new, unique medical discipline. In addition to its association with nanotechnology, it changes the fundamental paradigm of disease in medicine from being at the organ level to being at the single-cell level. It is paradigm shifting in a number of ways. Befitting its nanotechnology origins, nanomedicine uses a bottom-up rather than top-down approach to medicine. Nanomedicine uses a cell-by-cell approach and uses biosensing and feedback control to safely regulate drug delivery.

It is necessary to make quantitative single-cell measurements of efficacy. Efficacy is broadly defined as anything that is helpful or is providing some kind of a positive therapeutic effect, either directly or indirectly, that can be done on a single-cell level. While traditional medical measures of efficacy remain relevant and useful, it is important for a nanomedical approach to remain focused mostly on what is happening at the single-cell level. These measurements may be structural or functional, but they allow us to determine the efficacy of nanomedical treatments at the single-cell level.

Nanomedicine is the intersection of the field of nanotechnology with the field of medicine. In order to understand the basis for this intersection, it is first important to learn a little bit about nanotechnology in general as well as a few fundamentals of medicine and specific fields of science and engineering. In this book, I will use an approach to teachingcalled the “spiral approach.” The idea is to first introduce a concept at a very simple level and then gradually peel away the layers to go into greater depth and level of understanding, like peeling back the layers of an onion. I will introduce basic concepts in earlier chapters and then go into much more detail in later chapters.

A number of different targeting molecules can be used to target nanoparticles to specific cells for diagnostics or therapeutics. The main categories are antibodies, peptides, and aptamers. Each targeting molecule type has its advantages and disadvantages. Targeting then needs to be quantitatively measured by single-cell technologies such as flow and image cytometry.

There are many challenges of proper drug dosing with nanodelivery systems. The first part of this discussion concerns how experts think about drug dosing with conventional drugs. In the second part, we need to consider the differences between nanodevices and traditional drug delivery, and pharmacokinetics using nanodrug delivery. Drug dosing uses scale-up methods from animal model data before testing on humans. New organ-on-a-chip and human-on-a-chip technologies may someday replace animal data.

Typically, there is an optimal dose for treating a diseased cell. But most conventional drug delivery systems have either exponential or biexponential decay characteristics. So-called timed-release drugs create a sawtooth drug delivery pattern, which is a big improvement but still less than optimal. What we really want is to be able to hold the drug delivery to as close to the optimal dose as possible over time. This can best be done using nanomedical systems with biosensing and feedback control systems.

This chapter describes quality assurance and regulatory issues and how different government agencies approach the problem of determining whether new nanomedical systems are safe and effective. Nanomedical systems are both a device and a drug. Testing in humans after animals occurs in precise regulatory stages of clinincal trials. Regulatory agencies also assess potential damage to the environment and monitor worker safety issues.