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Catalyzing Inquiry at the Interface of Computing and Biology
6 years, with much of the savings coming from reduced repetitive motion injuries and fewer health problems caused by allergen exposure.
In the future, modularization is likely to continue. In addition, fewer stand-alone robot arms are being used because the robotics necessary for sampling from conveyor belts are often integrated directly into clinical analyzers. Attention is turning from the development of hardware to the design of process control software to control and integrate the various automation components; to manage the transport, storage, and retrieval of specimens; and to support automatic repeat and follow-up testing strategies.
From a conceptual standpoint, automation for speed depends on two things—speeding up an individual process and processing many samples in parallel. Individual processes can be speeded up to some extent, but because they are limited by physical time constants (e.g., the time needed to mix a solution uniformly, the time needed to dry, the time needed to incubate), the speedups possible are limited—perhaps factors of a few or even ten can be possible. By contrast, parallel processing is a much bigger winner, and it is easy to imagine processing hundreds or even thousands of samples simultaneously.
In addition to quantitative speedups, qualitatively new data acquisition techniques are needed as well. The difficulty of collecting meaningful data from biological systems has often constrained the level of complexity at which to collect data. Biologists often must use indirect or surrogate measures that imply activity. For example, oxygen consumption can be used as a surrogate for breathing.
There is a need to develop new mechanisms to collect data, particularly mechanisms that can form a bridge from the living system to a computer system, in other words, tools that detect and monitor biological events and directly collect and store information about those events for later analysis. Challenges in this area include the connection of cellular material, cells, tissues, and humans to computers for rapid diagnostics and data download, bio-aided computation, laboratory study, or human-computer interactivity, and how to perform “smart” experiments that use models of the biological systems to probe the biology dynamically so that measurements of the spatiotemporal dynamics of living cells at many scales become possible.
A good example of future data acquisition challenges is provided by single-cell assays and single-molecule detection. Traditional assays can involve thousands or tens of thousands of cells and produce datasets that reflect the aggregate behavior of the entire sample. While for many types of experiments this is an appropriate approach, there are current and future biological research issues for which this does not provide sufficient resolution. For example, cells within a population may be in different stages of their life cycle, may be experiencing local variations of environmental conditions, or may be of entirely different types. Alternatively, a probe might not touch the cell type of interest, due to inadequate purification of a sample drawn from a subject that contains many cell types.32 For some biological questions, there is simply not a sufficient supply of cells of interest; for example, certain human nervous system tissue is highly specialized, and a biological inquiry may concern only a few cells. Similarly, in attempts to isolate some diseases, there may be only a few, or even only one, affected cell—for example, in attempts to detect cancerous cells before they develop into a tumor.
Many technologies offer approaches to analyzing and characterizing the behavior of single cells, including the use of mass spectrometry, microdissection, laser-induced fluorescence, and electrophoresis. Ideally, it would be possible to monitor the behavior of a living cell over time with sufficient resolution to determine the functioning of subcellular components at different stages of the life cycle and in response to differing environmental stimuli.
Today, this issue is addressed by the very labor-intensive process of “plucking” individual cells from a sample and aggregating them—a process that typically requires 104 to 105 cells when today’s assays are used.