In any field of science, new discoveries often depend on finding answers to fundamental questions. In drug discovery, that often means uncovering the differences between healthy and diseased cells and tissues and understanding the biological basis of cellular function and dysfunction at the molecular level.
Microscopes and imaging technology have evolved in synchrony with advances in computers and software applications, detectors, light sources, and labeling and detection systems. Microscopes have an increasingly important role in research aimed at illuminating what exactly happens, for example, when a virus infects a host cell, a ligand binds to a membrane receptor, or a tumor cell metastasizes.
The abundance of published articles featuring advanced imaging techniques, and grant awards to support the establishment and expansion of imaging centers are evidence of the critical role of microscope technology in biomedical research.
For example, The HIV Center at the University of Utah recently received a $21.8 million grant from the NIH to develop methods to image and study the structural biology of the AIDS-causing virus and to understand how it infects host cells, replicates, and spreads.
The Molecular Imaging Center at Washington University School of Medicine in St. Louis received a $7.1 million grant from the NCI. And the Dana-Farber Cancer Institute received a $10 million grant from the Massachusetts Life Sciences Center to expand its cancer imaging research program and to help establish the Molecular Cancer Imaging Facility, a research initiative aimed at developing new molecular imaging probes.
These sizable grants also emphasize the high cost of imaging technology, and one overarching goal expressed by developers of microscope systems is to bring down the cost of ownership and expand accessibility of the technology.
While the most advanced technology is available to the top biologists in the world, “we need to make it more financially and technically accessible to all biologists,” says Paul Goodwin, science director at Applied Precision, a GE Healthcare company.
In surveying the microscopy industry, several key trends emerge, most prominently an emphasis on increased resolution and the emergence of super-resolution technology and dynamic imaging in live cells and organisms.
The super-resolution methods that have emerged represent an alphabet soup of sophisticated techniques including structured illumination microscopy (SIM), stochastical optical reconstruction microscopy (STORM), spatially modulated illumination (SMI), ground state depletion (GSD), and stimulated emission depletion (STED).
Live-cell/organism imaging requires faster image acquisition to capture biological and physiological processes as they are happening, such as protein-protein interactions, cell migration, morphologic changes related to cell division or apoptosis, and ion-channel activity. Growing interest in live-cell imaging has spurred developments in related fields such as label-free imaging to enable less intrusive and disruptive methods that do not require exposure to large amounts of light likely to affect the biology and compromise the viability of cells.
Additional trends focus on enhanced quantitation, co-localization, and correlative microscopy, and the integration of different microscopy techniques in unified multifunctional systems. Advances in deep-tissue imaging and 3D microscopy reflect a trend in cell biology away from studying cells grown in monolayers to examining multicellular and tissue constructs to explore biology in a more natural, dynamic environment.
The challenges lie mainly in the ability of tissues to absorb and scatter light, and other factors that contribute to poor signal-to-noise ratios when imaging through tissues and aberrations that can compromise resolution.