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Japan's AIST Looks to Commercialize Spotter For Array Printing, MALDI-TOF Applications


Scientists at Japan’s National Institute of Advanced Industrial Science and Technology have developed an instrument that they claim can spot substrates for microarray-based applications and those in microplates for use in mass spectrometry.
Called the VPW-8nano, the spotter consists of eight capillaries at adjustable intervals that its creators claim can produce high-density chips or microplates with less source material than existing arrayers. Tsukuba-based AIST is now seeking partners to bring the spotter to the analytical instrument market in Japan.
According to Hiroshi Aoki, a research scientist in the measurement technology group of AIST's Research Institute for Environmental Management Technology, the VPW-8nano was developed specifically for use in mass spectrometry-based experiments and to fabricate biosensor arrays used in a risk-management system for chemical compounds.
Specifically, the capillary intervals of the VPW-8nano spotter can be varied from 9 mm to 0.9 mm for an outer capillary diameter of 360 nanometers. A syringe pump is connected to the capillary to suction or discharge a liquid sample through the tip of the capillary.
By completely removing the air remaining in the liquid-handling system, the sample-dispensing volume can be adjusted so that it supports a wide range of small-scale to large-scale operations, Aoki said. The application of the spotter for printing arrays was described in a paper earlier this year [Aoki H, et al. Variable-pitch dispensing workstation and its application to the preparation of microsensor arrays. Analytical Sciences. 2008 Jun;24(6):817-21].
Aoki told BioArray News last week that the spotter was developed to provide specific advantages for users spotting arrays and microplates.
“The most characteristic point of this spotter is its ability to dispense a small amount of solutions with high accuracy and to change the interval between capillary outlets, [which gives it] an advantage [over] commercially available spotters,” Aoki said.
Currently, array vendors use a variety of different methods to manufacture their products. Agilent Technologies, for instance, uses its SurePrint inkjet technology to print its own arrays, and chips for client companies, including Oxford Gene Technology, BlueGnome, Signature Genomic Laboratories, Millipore, and others. In addition, Roche NimbleGen, Illumina, and Affymetrix have developed internal methods for creating their chips.
But labs that spot their own arrays must rely on arrayers sold by companies such as Roslin, UK-based Arrayjet, which uses non-contact inkjet printing; and Billerica, Mass.-based Aushon Biosystems, which uses a more traditional pin-spotting approach.
Aoki said that the VPW-8nano spotter can spot on glass, metal, and plastic substrates a variety of solutions, including proteins, hydrolyzed proteins, and nucleotides. He said such flexibility could make it attractive to labs in the Japanese market interested in medical care or environmental testing..
“This mechanism is compatible with all commercially available microplates, and the sample container and substrate that have different alignment specifications can be flexibly connected,” he said.
While AIST's new spotter could be attractive to microarray users, it was actually developed largely to meet the needs of researchers performing mass spectrometry experiments, Aoki said.
“Generally, the optimum alignment specifications in microplates and sample substrates are different,” Aoki said. “For rapid dispensing sample solutions between them, the solutions are spotted on the substrates in the same alignment as the well alignment on the microplates,” he said.

“The present market in Japan for spotters is stagnant and saturated with those based on conventional specifications.”

According to Aoki, the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method has in particular been limited by the quality of spotters available.
“Analysis based on the conventional dispensing technology has a trade-off relationship where the rapidity [of the spotter] counteracts the high precision and integration of the dispensing operation,” Aoki said. “Using this spotter rather than the conventional ones, the sample can be dispensed in narrower intervals and the substrate and analytical equipment, including MS, can be downsized.
“The spotter also makes high-precision external standard mass calibration possible due to spotting the sample and standard within an extremely short distance,” he added.
Aoki said that current MALDI-TOF methods use approximately 500 nanoliters of liquid sample per spot, which is what current dispensing technology requires to create spot diameters of around 2 mm and spot intervals of approximately 4–5 mm.
“These values are apparently too large in comparison with the 100- 300-nanometer laser irradiation diameter of the usual” MALDI-TOFs, Aoki said. “The space on the substrate that is not used for the measurement is being wasted.”
Aoki also said that the spotter's specifications could enhance the standard mass calibration method generally used in MALDI-TOF MS, where a reference compound of a known mass number is mixed with the liquid sample.
He said that, by dispensing the reference compound onto the neighborhood of the sample spot within an extremely short distance, the spotter could perform external mass calibration. “Because the existing mass analytical equipment is a product of compromise designed to fit the current dispensing technology specifications, the inherent performance cannot fully be utilized,” he said. 
Big in Japan?
According to Aoki, AIST is now looking to partner with Japanese companies that could bring the VPW-8nano to the local market after securing licenses through AIST's technology-licensing organization. Aoki said that AIST is specifically searching for a “major company for analytical equipments in Japan.”
At the same time, he said, the market for such instruments in Japan is not dynamic. “The present market in Japan for spotters [is] stagnant and saturated with those based on conventional specifications,” Aoki said. “But users might want to use the spotters which can dispense solutions between microplates and sample substrates with different alignment specification, like our spotter.”
“We think that the new spotter will make a new market and be attractive to users who are engaged in drug discovery, proteomic, and metabolomic analysis and other analysis based on a small amount of samples,” he added.
So far, AIST has been visited by “several drug- and MS-manufacturing companies” to evaluate the spotter for potential commercialization Aoki said. He declined to name the companies.
As AIST looks to bring the VPW-8nano to market, Aoki said that it will look to expand into other application areas and look to reduce sample requirements and make its capillaries more flexible for different printing projects.

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