Cytokine ELISPOT assay technology

I've been learning about the technology involved in performing immunological assays. Cross-disciplinary work fascinates me, and it always has. High-performance automation is extremely cross-disciplinary in nature, and this is true of immunological laboratory robotics as well. It ideally requires a proper understanding of chemistry, biological systems, electromechanical systems, computer vision and software engineering -- hence my interest in this field.

The ELISPOT process

The enzyme-linked immunospot (ELISPOT) assay is a flexible and highly sensitive tool for analyzing the immunological secretions of peripheral blood and lymphoid cell populations. This process allows for the detection, enumeration, and characterization of individual cytokine-secreting cells within cultured cell populations.

In the case of a cytokine assay, a culture plate is coated with anti-cytokine antibodies. The cells are introduced, under conditions which cause them to secrete the cytokines. These cytokines bind to the antibodies in question, after which the cells are removed. An enzyme-labeled anti-cytokine is then applied to the bound cytokines, and a chromogenic (i.e. color-generating) substrate is applied to anti-cytokines. This substrate creates colored spots which can be detected via machine vision. (This process is graphically depicted here.)

ELISPOT technology

In order to be truly effective though, the software techniques used must be designed to make maximal use of machine vision techniques and man-machine interface usability. This can be tricky, as the individuals who develop the software are generally not the types who would be using it on a regular basis. UI design is an art form unto itself, and its difficulty is compounded when such disparate fields and biochemistry and software engineering are involved.

This necessitates the development of readers or analyzers which can perform the analysis at high speed, and with high accuracy. This avoids most of the tedium involved in this process, and if scientifically validated statistical techniques are used, the subjectivity involved can be eliminated as well.

ELISPOT applications

The ELISPOT assay was originally developed for analyzing specific antibody-secreting cells; however, it has been adapted for enumerating cells which secrete other effector molecules, such as cytokines, chemokines and granzymes. The high sensitivity and flexibility of this technique are among the attractive features of the ELISPOT assay method.

Laboratory automation

A single experiment can involved dozens, or even hundreds, of plates. Manual loading and unloading of these plates can be tedious in the extreme, and can lead to gross human errors. Ditto for the washing and chemical preparation of these plaets. This is a classic situation wherein robotic automation can greatly improve both accuracy and throughput.


More info...

Information on reagent sets and an expanding glossary of immunological terms might prove useful to the layman.