Massachusetts Institute of Technology (MIT) chemists have developed a high-throughput and inexpensive method for the multiplexed detection of biomolecules by using multifunctional particles. This method could be used to screen for millions of different biomolecules and lead to new and low-cost clinical bedside diagnostics: no more need to wait a day or more before a lab analysis. The particles developed at MIT contain a barcoded ID and one or more probe regions that turn fluorescent when they detect specific targets in a test sample. The researchers think that this method, based on highly customizable particles, could also be used for drug discovery or genetic profiling.
This research has mainly been done by Daniel Pregibon, a graduate student in chemical engineering at MIT, under the supervision of Patrick Doyle, an associate professor of chemical engineering, and within his research group.
On the left, you can see an example of such a multiplexed analysis using single-probe encoded particles. The particles were loaded with DNA oligomer probes. Shown are representative fluorescence images for single-probe particles after a 10-min incubation with both fluorescent-labeled targets. (Credit for image: Daniel Pregibon, MIT)
Even if the researchers are discreet on their particles, they offer some clues: "As two streams of monomers (liquid precursors loaded with fluorescent dye or molecular probe) flow side by side through a microfluidic device, ultraviolet light repeatedly strikes the streams. A chemical reaction initiated by the light causes the liquid to solidify, forming a single particle with two distinct ends. Each particle takes on the shape of a "mask" (similar to a transparency film) through which the UV light is aimed. One end of each particle is a fluorescent "dot-pattern" barcode that reveals what the target molecule of the particle is, and the other end is loaded with a probe and only turns fluorescent if the target molecule is present. The particles can also be designed to each test for multiple targets, by adding several unique regions."
Now, why this method will be fast to use and the future detection tools inexpensive?
To rapidly "read" the particles, the researchers designed a custom "flow cytometer" using a microfluidic device and standard microscope. In this flow-through system, the oblong, disk-like shape of the particles ensures that they are precisely aligned for accurate scanning. Each time a particle flows past a detector, its barcode is read and the corresponding target is quantified.
The microparticles are inexpensive because they can be produced efficiently in a single step. The design of the particles also makes the scanning devices cheaper. With multiple distinct regions, the barcode can be read and the target quantified using a single fluorescent color, which greatly simplifies detection.
For more information about the subject, this research work has been published by Science under the title "Multifunctional encoded particles for high-throughput biomolecule analysis" (Volume 315, Issue 5817, Pages 1393-1396, March 9, 2007). Here are two links to the abstract and to the full paper (PDF format, 4 pages, 281 KB). This article contains additional illustrations which are worth looking at.
Sources: Massachusetts Institute of Technology news release, via EuerkAlert!, March 8, 2007; and various websites
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