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  • Review Article
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Encoding microcarriers: present and future technologies

Nature Reviews Drug Discovery volume 1, pages 447–456 (2002)Cite this article

Key Points

  • Over the past few years, in the fields of drug discovery, drug screening and diagnostics, as well as in combinatorial chemistry, many microcarrier-based multiplex technologies have arisen in which the compounds to be screened are attached to the surface of microcarriers. Each microcarrier has to be encoded according to the compound that is attached to its surface. Decoding the microcarrier reveals the identity of the surface-bound compound. The encoding methods can be classified as follows:

  • Spectrometric encoding methods are those technologies that allow the microcarriers to be decoded by placing them directly into a spectrometer. This can be achieved by using either spectrometric chemical tags or an optical encoding strategy, in which the absorption or emission spectrum of the microcarrier determines its identity.

  • Electronic encoding methods make use of radio-frequency memory tags that can transmit their identity (ID) code as a radio-frequency pulse towards a transceiver.

  • The graphical encoding methods are promising with regard to the number of unique codes that can be generated. Here, the microcarriers are encoded by the spatial modulation of a material or its properties.

  • Finally, it is possible to discriminate between microcarriers on the basis of their physical properties 'as a whole', such as size, density, composition and so on.

  • Which of those encoding strategies will turn out to be the most successful will depend not only on the number of unique codes that can be generated, but also on the versatility of the microcarriers to be applied in various assays.

Abstract

In answer to the ever-increasing need to carry out many assays simultaneously in drug screening and drug discovery, several microcarrier-based multiplex technologies have arisen in the past few years. The compounds to be screened are attached to the surface of microcarriers, which can be mixed together in a vessel that contains the target analyte. Each microcarrier has to be encoded to know which compound is attached to its surface. In this article, the methods that have been developed for the encoding of microcarriers are reviewed and discussed.

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Figure 1: The need to encode microcarriers.
Figure 2: Colloidal encoding.
Figure 3: Luminex xMAP system.
Figure 4: Bead-based fibre-optic array.
Figure 5: Alternative fluorescence encoding methods.
Figure 6: Electronic encoding.
Figure 7: Laser-etched barcodes.
Figure 8: Metallic nanorods.
Figure 9: Spatial selective photobleaching.

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Acknowledgements

We thank Dr. C Roelant for many fruitful discussions about progress in the fields of drug discovery and diagnostics.

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  1. Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Harelbekestraat 72, Ghent, 9000, Belgium

    Kevin Braeckmans, Stefaan C. De Smedt & Joseph Demeester

  2. Tibotec –Virco, Generaal de Wittelaan L11 B3, Mechelen, 2800, Belgium

    Marc Leblans & Rudi Pauwels

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Glossary

TARGET ANALYTE

The substance whose properties are being determined in an analysis.

EMISSION SPECTRUM

The spectrum of possible emitted wavelengths of a fluorophore.

CHROMOPHORE

An atom or group of atoms that has a specific light-absorption spectrum, which is usually in the visible spectrum.

FLUOROPHORE

A molecule in which the three stages of fluorescence occur. First, a photon from an external source is absorbed, which causes an excited electronic singlet state. This state exists for a finite time period, typically 1–10 ns, during which the fluorophore is subjected to interactions with its environment that result in a relaxed singlet state. Finally, a photon of lower energy (and hence a longer wavelength) compared with the absorbed photon is emitted.

COLLOIDAL FORCE

The long-range force between colloidal particles; that is, particles smaller than a few micrometres in diameter. The origin of colloidal forces can be, for example, electrostatic, electrodynamic or steric.

POLYELECTROLYTE

A macromolecule in which a substantial portion of the constituent units have ionizable or ionic groups, or both.

FLUORESCENCE RESONANCE ENERGY TRANSFER

A distance-dependent interaction between the electronically excited states of two dye molecules, in which excitation is transferred from a donor molecule to an acceptor molecule without emission of a photon.

EXCITATION SPECTRUM

The spectrum of possible wavelengths for the excitation of a fluorophore.

ISOTROPIC

Equal in all directions.

FLOW CYTOMETER

An instrument that measures properties, such as light scatter and fluorescence, of microscopic objects, such as cells, as they move or flow in liquid suspension.

PHOSPHORESCENCE

This is essentially the same process as fluorescence, but with a longer excited singlet state — lifetime is typically 10−3 to 102 s.

PHOTOCHROMISM

A reversible photoisomerization between two isomers that have different absorption spectra.

REFRACTIVE INDEX

The ratio of the velocity of propagation of an electromagnetic wave in a vacuum to its velocity in the medium.

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Braeckmans, K., De Smedt, S., Leblans, M. et al. Encoding microcarriers: present and future technologies. Nat Rev Drug Discov 1, 447–456 (2002). https://doi.org/10.1038/nrd817

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