Analytical chemistry

Home diagnostics to music

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Fed up with sitting in the doctor's surgery among all those sneezy patients, waiting for the results of a health check? With the latest technology, you could one day perform bioassays on your home compact-disc player.

Biosensors are under commercial development for all sorts of applications — detecting human and animal pathogens, measuring clinical markers for heart attack and cancer, and monitoring environmental pollutants. The most effective way to put biosensors into the hands of potential customers, especially those with limited budgets, might be to modify the technology so that it can run on everyday devices, rather than on specialized apparatus. Popular electronic gadgets such as palm-sized computers, flatbed scanners and DVD players could potentially be converted into low-cost, battery-operated, user-friendly biosensors. Reporting in Analytical Chemistry, Li et al.1 describe a notable advance in this direction: a system for running assays on standard compact discs that uses free CD-quality-analysis software to detect and quantify biological binding events.

With data-reading optical elements and electronics already incorporated into CD players, it is easy to imagine that sample delivery systems could be integrated into these devices to provide a system for running assays on discs. In particular, researchers developing microfluidics technology have shown that centrifugal force can be used to move fluids through compartments in a spinning disc2,3. The first such systems required external devices to read out results from disc-based assays, but the best readers would be standard-issue machines such as those found in homes or cars.

Although Li et al.1 are not the first to run bioassays on a disc, or to read results using a standard CD player, they are the first to have integrated most of the elements required to do both. Building on previous findings4,5,6,7, they report a gentle and widely applicable method for attaching biorecognition molecules — which can bind to a wide variety of medically important target molecules — to the surface of a CD. This method involves oxidizing the polymeric surface of the disc to form chemical groups to which biotin molecules can be tethered. The surface-bound biotin molecules bind specifically to streptavidin proteins, which can subsequently be used to immobilize various biorecognition molecules. The authors designed their system so that, in the presence of a target molecule, a surface-bound complex forms that includes gold nanoparticles. The nanoparticles reflect light and thus can generate an optical signal. But in practice, the nanoparticles are too small to be detected by CD players. Li et al. therefore added an extra step to their protocol, in which larger silver particles are grown around the gold nanoparticles, providing a detectable proxy for the binding of target molecules.

Perhaps the real breakthrough in this work1 is the digital readout protocol. The data on every pre-recorded audio CD are encoded in such a way that errors can be detected and corrected by CD players, using a standard algorithm. For example, scratches up to about 8.5 millimetres long can be compensated for during playback. The silver particles that are associated with the formation of target complexes in Li and colleagues' system obscure data pre-recorded on the CD, and so can be detected as errors (Fig. 1). Furthermore, because each block of data on a CD is associated with a physical position on the disc, these errors can be tracked to their locations. Li et al. therefore used free diagnostic software to analyse the error information measured by the CD player reading the disc. By plotting the rate of error detection against the distance from the centre of the CD, the formation of target complexes at all points on the CD's surface can be quantified.

Figure 1: Musical bioassays.
figure1

Each track on a CD stores data as a series of pits in a light-sensitive dye layer that is backed by a reflective metal layer. CD players read the data by scanning the dye's surface through a polymer layer. Li et al.1 have developed a system for running binding assays on standard CD players. 'Capture molecules' attached to the polymer surface of a CD bind to specific molecular targets. Gold nanoparticles attached to the targets nucleate the formation of larger silver particles, which prevent the laser beam of a CD player from reading the data on the disc. This creates an error in the retrieved data, which can be detected by the CD player. The authors use free, CD-quality-analysis software to detect and quantify binding events across the surface of the CD. (Figure modified from ref. 1.)

Methods for acquiring data from a disc-based assay using a standard CD reader8 or specially written error-determination software9 have been reported previously, but Li and colleagues' use of freely available software opens up such assays for widespread use. And by demonstrating that three different software packages can be used for detecting spots of bound targets, the authors show that their technique need not be restricted by the availability of any single error-detection program.

Using their biochemical and analytical strategy1, the authors performed assays to detect the binding of single-stranded DNA to complementary strands and to detect the binding of antibodies to antigens. The detection rate increased with the concentration of the targets, suggesting that the assays can indeed produce quantitative results. After carrying out comparison experiments, Li et al. claim that the sensitivity of their technique is tenfold higher than that of fluorescence-based methods. This assessment may not be valid, as they placed ten times more target molecule in the microfluidic channels for the CD reader than in the channels for their fluorescence assays — but this is a minor criticism.

Only one piece of the puzzle now remains to be slotted into place: microfluidic structures must be integrated into CDs for sample processing and reagent storage in a format that can be run in a standard CD player. Figuring out how to do this without compromising the detector's function is a tough problem. An additional transparent layer would need to be attached to the disc to either contain or constrain microfluidic channels, buffers and freeze-dried reagents. Potential fabrication methods include injection moulding, embossing or casting10, but any such modifications to the original disc must be done in a way that does not damage the underlying metal or light-sensitive layer.

If fluidics were integrated into the disc by removing material from the thick polymer layer, the sensitivity of the technique might actually be increased: the binding events would occur closer to the reflecting layer of the disc, on which the detecting laser is focused. But local changes in the thickness and refractive index of the polymer layer might also alter the focal distance of the laser, reducing sensitivity. Furthermore, light scattering off the walls of the microfluidic structures might produce signals that are difficult to distinguish from binding signals.

One solution would be to make all the surfaces forming the microfluidic channels from materials that have the same refractive index, and then to fill the channels with a fluid of similar refractive index. This is much easier said than done. Alternatively, the fluidic layer could be made to be removable. This would necessitate a two-spin assay — one to run the assay, and another, without the fluidic layer, to detect the results. The removal of the fluidic layer between spins would have to be performed in a way that doesn't damage the sensing surface of the disc, but such handling by the user would best be avoided.

Clearly, there is much work to be done, yet the integration of bioassays into consumer electronic devices has a bright outlook. Perhaps we really will eventually be able to recreate the experience of a doctor's surgery at home: not only will we be able to run a quick and inexpensive biological test in our own living room, but the analytical device will also provide the waiting-room background music.

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Erickson, J., Ligler, F. Home diagnostics to music. Nature 456, 178–179 (2008) doi:10.1038/456178a

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