Big Potential in Small Sample Sizes

Microliter spectrophotometry is a technique used to measure extremely small sample sizes, but its market potential is anything but small. Recent activity in the market has reflected both large and small companies’ recognition of the prospects of microliter spectrophotometry. In October, Thermo Fisher Scientific acquired NanoDrop (see IBO 10/15/07), the market leader. Next year, GE Healthcare will introduce the NanoVue spectrophotometer. The NanoVue is manufactured by Harvard Bioscience’s British subsidiary, Biochrom. Harvard Bioscience estimates the microliter spectrophotometry market to be worth $50 million and growing at 20% per year. And UK firm Picodrop launched its microliter spectrophotometer, the Picodrop, earlier this year and will bring the instrument to the US in January.

The principles behind microliter spectrophotometry are the same as for standard spectrophotometry: different light spectra are passed through a sample and the absorbance or transmission of this light provides information about the sample, such as concentration levels. As Jonathan Redfern, CEO of Picodrop, explained, this component of microliter spectrophotometry was made possible by the development of fiber optic–coupled spectrophotometers, which have been available for several years. The important difference in microliter spectrophotometry is the sample size: current sample sizes promised by microliter spectrophotometry manufacturers range as low as 0.5 µl, and as Dr. Redfern said, the competition to bring sample sizes lower should be a feature of the market going forward. In addition to Thermo/NanoDrop and Harvard Bioscience/GE Healthcare and Picodrop, other companies offering microliter spectrophotometry include Implen GmbH and Analytik Jena AG.

Differentiating the instruments are the different methods used for holding the sample for analysis. NanoDrop’s spectrophotometers use an arrangement of hydrophobic surfaces and surface tension in which the sample directly bridges a gap between two fiber optic cables. With Analytik Jena’s ScanDrop and Harvard Bioscience’s NanoVue, the sample is placed directly on a sample window. In the NanoPhotometer, the sample is forced into a small gap between the measurement window and a reflecting mirror. Implen’s NanoPhotometer uses a Biochrom spectrophotometric module, but has different software and internal components. Finally, the Picodrop is designed to scan samples while they are still inside the pipette, using the company’s UVpette tips. All of the instruments’ sampling setups, with the exception of NanoDrop’s instruments, allow end-users to recover the majority of their samples, which can be an added benefit.

Another differentiating factor is the sample’s exposure to air. One problem that can arise with microliter samples exposed to air is evaporation, which can change concentration levels. Implen and Picodrop’s sampling configurations, for example, do not expose samples to open air, keeping samples stable for minutes and allowing for kinetics analyses. However, as David Parr, managing director of Biochrom, explained, “the main application of these products is RNA and DNA quantification, and purity and proteins quantification, all of which require a single measurement which takes less than 10 seconds. Under these circumstances, evaporation is not an issue. If a kinetics experiment were a requirement, where a number of readings are taken at set intervals so that the elapsed time might be a matter of minutes, then evaporation would be a major issue.”

When larger sample sizes are available, cuvette-based spectrophotometers still offer better performance. As Dr. Parr explained, microliter spectrophotometers “are ideal for applications where there is only a small amount of highly absorbing sample. Where plenty of sample is available, this technology would not be used since the performance of conventional cuvette technology will always be better.” In order to address both kinds of applications, Implen and Analytik Jena’s products can use cuvettes for larger samples in addition to cuvette-free analyses of microliter samples. Another feature of spectrophotometry with larger samples is the capability for performing high-throughput applications. Microliter spectrophotometry typically does not allow for high throughput, but Picodrop has recently developed a high-throughput offering. Called the Seadragon, the product is the result of a collaboration with Gilson and uses Gilson’s liquid handling robotics.

For all of the companies IBO spoke with, DNA and RNA analysis are the most common applications for their microliter spectrophotometry products, but protein research is one of the fastest-growing applications. Thomas Sahiri, managing director of Implen, explained that the company would be releasing new consumables for protein and cell analysis application markets: “We will be launching a new disposable cell called DiluCell in the first quarter of next year, which will allow users to do cell density and difficult protein sample measurements without a physical dilution.” Dr. Redfern also said that a large proportion of his customers have expressed interest in using the Picodrop for proteins.

Across the range of applications, microliter spectrophotometry is most widely used in academic and other research markets. Dr. Sahiri added that Implen also “has been very successful in the clinical diagnostics environment, since the NanoPhotometer can be easily integrated in accredited environments offering the right tools to follow regulations.” For end-users, the most attractive features of microliter spectrophotometry are the conservation of samples and ease of analysis. In a press release announcing the NanoDrop acquisition, Thermo Fisher Scientific CEO Marijn Dekkers noted that Thermo was drawn to NanoDrop because of the opportunity to offer Thermo’s customers the capacity to reduce sample preparation time and to cut down the amount of sample needed for experiments.

The companies involved in the microliter spectrophotometry industry are confident that strong growth is on the horizon. Dr. Parr estimated near-term growth of “around 20%, driven by the convenience of the product to carry out these life science applications quickly—and the growth in carrying out such applications.” Dr. Sahiri had a similar outlook: “For the next years, we are expecting a double-digit growth rate of micro and submicroliter applications in the UV/Vis area. This is mainly triggered by protein labs that are discovering . . . [varieties of submicroliter spectrophotometry-based analyses] as a sensible alternative to protein assays for precious samples.” Dr. Redfern was perhaps even more confident, comparing microliter spectrophotometers’ future to another life science laboratory mainstay: “The only other piece of equipment that has such a wide general demand is the thermal cycler, which had a similar growth pattern in the early 1990s.”

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