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  • Review Article
  • Published:

Microscopic imaging techniques for drug discovery

Nature Reviews Drug Discovery volume 7, pages 54–67 (2008)Cite this article

Key Points

  • Recently disclosed microscopic imaging techniques are helping to better describe how disease processes unfold and how potential therapies might intervene. Innovative technologies are improving spatial resolution, increasing tissue penetration, overcoming physical access issues and enhancing experimental throughput.

  • Notable recent trends include the development of super-resolution microscopes, the incorporation of multiphoton techniques into intravital and fibre-optic microscopy, and the automation of microscopy and image analysis for high-content screening.

  • A renaissance in intravital or in vivo microscopy is helping to better characterize disease states and assess the efficacy of therapeutic interventions. In particular, in vivo microscopies are achieving better resolution at greater depths or from within less accessible tissues. This renaissance is helping to emphasize both pharmacological and clinical relevance in animal and tissue models.

  • The miniaturization of fluorescence microscopy by fibre-optic technologies is also helping to implement less invasive optical readouts and thereby enable the development of improved chronic or long-term animal models.

  • The capability to image the in vivo treatment response to test compounds, especially in animal models of disease, is likely to be an important addition to the toolbox of discovery scientists. In particular, imaging the whole-body treatment response is a useful way of simultaneously quantifying the efficacy, time course and the specificity of therapeutic candidates. It is also potentially useful in identifying off-target effects and liabilities.

Abstract

Microscopic imaging can enhance the drug discovery process by helping to describe how disease processes unfold and how potential therapies might intervene. Recently introduced technologies, and enhancements to existing techniques, are addressing technical issues that have limited the usefulness of microscopic imaging in the past. In particular, these innovations are improving spatial resolution, increasing tissue penetration, overcoming physical access issues and enhancing experimental throughput. Notable recent trends, which are discussed in this article, include the development of super-resolution microscopes, the incorporation of multiphoton techniques into intravital and fibre-optic microscopy and the automation of microscopy and image analysis for high-content screening. Together, these developments are augmenting the existing assays and disease models that are used in early drug discovery and, in some cases, enabling new ones.

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Figure 1: Microscopic imaging technologies for drug discovery.
Figure 2: Super-resolution microscopes.
Figure 3: New optics for intravital microscopy.
Figure 4: Disease biology applications of intravital microscopy.
Figure 5: Fibre-optic imaging technique hierarchy.
Figure 6: Fibre-optic fluorescence imaging technology and applications.

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Acknowledgements

The author would like to thank B. Brission and A. Goodacre for their assistance in providing material for this Review. The editorial assistance of P. Prack and V. Shen is also greatly appreciated.

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  1. Biological Imaging Development Center, 513 Parnassus Avenue, University of California, San Francisco, 94143-0511, California, USA

    Andrew Bullen

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FURTHER INFORMATION

UCSF Biological Imaging Development Center

Glossary

Numerical aperture

The numerical aperture is a measure of the light-gathering capability of an objective lens.

Moiré fringe

The Moiré effect is a well-known phenomenon that occurs when repetitive structures such as screens, grids or gratings are superposed or viewed against each other.

Multiphoton microscopy

This is also called two-photon excitation microscopy or nonlinear optical microscopy.

CCR7

CCR7 is a chemokine receptor involved in the trafficking of B and T lymphocytes and dendritic cells.

Pyelonephritis

This is an infectious condition of the kidney whereby bacteria spread throughout the lumen of infected nephrons into surrounding tissues. It is accompanied by an acute inflammatory response and can result in significant tissue damage.

PET

Positron-emission tomography. A noninvasive, molecular imaging technique of high sensitivity that detects species labelled with positron-emitting radionuclides in vivo.

MRI

Magnetic resonance imaging. The use of radio waves in the presence of a magnetic field to extract information from certain atomic nuclei (most commonly hydrogen, for example, in water). Tissues can be differentiated by differences in their water densities.

Flow cytometry

Flow cytometry is a well-established technique that is used to count, characterize and sometimes sort cells that are suspended in a stream of fluid.

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Bullen, A. Microscopic imaging techniques for drug discovery. Nat Rev Drug Discov 7, 54–67 (2008). https://doi.org/10.1038/nrd2446

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