Exploiting the phenomenon of linear dichroism (LD)
Linear Dichroism occurs when there is a difference in absorbance, by a sample, of two light beams which are polarized in two different directions. The polarization directions are usually parallel to an alignment (fluid flow) direction and at right-angles to this. LDL’s technology exploits this phenomenon by aligning a long thin scaffold molecule, achieved by flowing it in a liquid, and measuring the degree of alignment using LD. If the scaffold is modified to bind to a target (e.g. by immobilizing antibodies on it) then, in the presence of the target, this specific sensor molecule binds to the target and thus changes the alignment which in turn produces an LD signal change.
Long, thin sensor molecules (phage) are aligned under flow in a liquid sample. Alignment of the sensor molecules depends on the amount of target present. In this example the target is a bacterium. The degree of de-alignment (and therefore the amount of target) can be measured by LD. This works by measuring the amount of light (polarized parallel and perpendicular to the flow direction) that passes through the sample. We measure this using a hand-held reader.
The signal change happens quickly (less than a minute) and indicates how much of the target is present. The scaffold molecule that we use is a bacteriophage or “phage”. Phages are naturally occurring viruses which infect specific host bacteria.
The advantages of using phages are many, and include the fact that they are simple and economical to produce, robust (our phages can withstand high temperatures and are impervious to many harsh chemicals), and monodisperse. This last point means that we have a population of molecules that have the same size and properties (including the chemical groups on the surface that we use to make them specific to the targets) and this allows us to modify them for our purposes with a high level of control.
Note that in our diagnostic applications we are using these desirable properties of the phages and not their ability to infect bacteria, which is destroyed when we change them into detector molecules by the addition of, for example, antibodies, DNA and/or dyes.