Shedding New Light on Cells Nanoluminescent Tags

Biologists have any number of reasons to be interested in the movements of particular groups of cells and other structures as they move through the body or even through a sample in a dish. Tracking movement can help them to determine how well drugs are being distributed and how substances are metabolized. But tracking a small group of cells as they move through the body is an essentially impossible task. A needle in a haystack is at least a chunk of dense metal in a mound of light biomass; you can find it by sifting or by using a metal detector. Cells have no significant material differences from one another and are typically of similar size and shape to other cells of their type. Unless you can actually attach something visible and unique to a cell, it will disappear into the body like a grain of sand into a beach.

In the past, scientists got around this problem by dyeing cells. If a sample of cells is green and all the other cells are more or less clear, it's easy to spot the sample. Organic dyes that have been used in the past can be toxic and must still be excited with light of a certain frequency to cause them to fluoresce. More recently, these dyes have been replaced with proteins that naturally fluoresce green or yellow, but these proteins must still be excited by light of the right frequency in order to operate. Different color dyes and proteins absorb different frequencies of light. Consequently, if you have multiple samples that you need to track at the same time, you may need as many light sources as you have samples. This can become quite a problem.

A. Paul Alivisatos, Moungi Bawendi, and their groups addressed this problem with the introduction of what are now often called luminescent tags. These tags are quantum dots often attached to proteins to allow them to penetrate cell walls. These quantum dots exhibit the nanoscale property that their color is size-dependent. They can be made out of bio-inert materials (materials that do not interact with life processes and are thus nontoxic) and can be made of arbitrary size. This means that if we select sizes where the frequency of light required to make one group of nanodots fluoresce is an even multiple of the frequency required to make another group of tags fluoresce, both can be lit with the same light source. At one stroke, these tags solve two major problems of the old organic dyes: toxicity and the ability to use more than one color of tags at the same time with a single light source.

The science behind luminescent tags is elegantly simple and shows how easily newly discovered properties at the nanoscale can be made practical. Bawendi and Alivisatos have gone on to found Quantum Dot Corporation where this discovery forms the core of their Qdot product. In a Qdot, the quantum dot is surrounded with a shell that protects it from its environment and amplifies its optical properties. The resulting structure can be attached to various different carriers to transport it to whatever it should tag. Figure 8.1 shows how this works.

Figure 8.1. Schematic of Qdot probe..

Courtesy of Quantum Dot Corporation

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