When solving engineering problems, Leonardo da Vinci would often look to nature for inspiration.  Long after he died, and in the English speaking world, this sort of approach was Christened biomimetic problem solving.  It is used by engineers when designing the shape of aeroplanes [1] and by synthetic organic chemists in preparing compounds that appear in nature [2], as well as their analogues.

The inspiration for producing molecular tools for research or medical applications using nature as an example is still apparently rather novel.  A recent example of this is the use of Quantum Dots.  Although a term like quantum dots sounds rather fun, it tells us little about what they are or what they do.  That they are, is a small amount (dot) of a compound not found in nature, that is surrounded to a particular type of amphiphile (lipid) that has been designed so intricately that it hardly bears comparison with naturally-occurring lipids.  This means the QD is rather like the micelles seen in soap, but with an inorganic compound in the centre.  What quantum dots (often known as QDs) do, is respond to particular wavelengths of light in a way that none of the rest of the material in the cell does. This makes them very clear and thus easy to detect.

Figure 1. Examples of amphiphiles that are used to surround fluorescently-active quantum dots [3]. These dots fluoresce at 535 nm and are relatively stable in biological systems as they are relatively small with respect to other quantum dots. The head group part of the amphiphilic section is similar to that in phosphatidylcholine. The end of the lipophilic end is bonded covalently to the quantum dot, and it is this interaction that is often damaged, leading to destruction of the dot.

Figure 1 shows some examples of quantum dots from a recent paper in Nature Chemistry [3] that documents research into the use of quantum dots as imaging tools.  The compound used for the dot, cadmium selenide (CdSe, sometimes doped with zinc sulphide, ZnS [3]), is utterly unknown in natural biological systems and perhaps for this reason the components are carcinogenic and require all sorts of precautions during use.  However, the lipid mono-layer covering of the CdSe means that Zhu et al. and many others have been able to use quantum dots for imaging in live cells [3].  The quantum dot itself is both sufficiently different from its surroundings and fluorescent enough to be used to detect very small numbers of cells.  However, the compound in itself requires protection in order to have specificity in biological systems.  A mono-layer of synthetic lipids is used to provide a barrier between the toxic compound and the aqueous system in which it is suspended.  The self-assembly properties of lipids mean that the system can remain intact under physiological conditions, and thus be transported through bilayers and between membrane compartments [3].

The fact that such quantum dots can be stabilised through the use of specially designed lipids increases their stability to a point that means that we can gain a sharper insight into a variety of processes in live cells.  The dots shown above last longer and so the relative intensity of the fluorescence can be used to indicate concentration of the dots with respect to the amount put into the system.  Studies to date have found that these markers can be used to track enzyme activity [4], which has applications in detecting given diseases.  Perhaps more fundamentally, quantum dots can be used to look at cells during gene expression, and thus track whether particular proteins are being made, and thus provide evidence for genetically-determined disease [5].  If this is the capability with current technologies, what will we see with improved stability and specificity?  The future of quantum dots is not just bright, it is fluorescent.


[1] “Airbus presents a panoramic view of 2050” http://www.airbus.com/newsevents/news-events-single/detail/airbus-presents-a-panoramic-view-of-2050/
[2] Helen C. Hailes, Ralph A. Raphael, James Staunton, Tetrahedron Letters, 1993, 34, 5313-5316. http://www.sciencedirect.com/science/article/pii/S0040403900739839
[3] Zheng-Jiang Zhu,Yi-Cheun Yeh, Rui Tang, Bo Yan, Joshua Tamayo, Richard W. Vachet, Vincent M. Rotello, Nature Chemistry, 2011, 3, 963-968.
[4] Stuart B. Lowe, John A. G. Dick, Bruce E. Cohen, Molly M. Stevens, ACS Nano, 2012, 6, 851–857.
[5] James E. Ghadiali, Stuart B. Lowe, and Molly M. Stevens, Angewantde Chemie International Edition, 2011, 50, 3417 –3420.