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Spanish Researchers Using Scienion Arrayers to Develop Nanomechanical Biosensor Platform

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Scienion said this week that the Bionanomechanics Lab of the Madrid-based Microelectronics Institute is using its SciFlexarrayer to produce nanomechanical biosensors for genetic analysis in collaboration with Mecwins, a Spanish technology company.

Montserrat Calleja, head of the department of devices, sensors, and biosensors at the Bionanomechanics Lab, told BioArray News that the Scienion instrument will be used to spot biomolecules on gold-coated silicon microcantilevers — beams that are supported by a biochip at one end and that carry molecules at the other end of the structure or along its length.

The researchers envision the new biosensors being used in diagnostic applications, and are currently developing an assay for Mycobacterium tuberculosis detection, Calleja said.

According to Calleja, the lab decided to use Scienion's arrayer because it "provides the needed flexibility to address cantilever sensors of almost any size and design," and, in particular, because the instrument's inkjet head "does not contact the surface of the fragile devices."

Scienion said the Bionanomechanics Lab is using its arrayer to immobilize thiolated single-stranded DNA onto the microcantilevers, producing a homogeneous self-assembled monolayer on each cantilever. After incubating the cantilevers with complementary DNA sequences, hybridization results in a deflection, or bending, of the cantilever that is detected with an optonanomechanical read-out platform called Scala being commercialized by Mecwins, also based in Madrid. According to Mecwins' website, Scala is capable of detecting hundreds of biomolecules simultaneously in a 96-well microplate format. The company's system is based on technology licensed from Calleja's lab.

Calleja said that Mecwins' system is capable of detecting the bending of hundreds of microcantilevers in a "one-shot measurement," and is sensitive enough to detect DNA hybridization without the need for labels or prior PCR amplification. She added that protein detection can be achieved without labeling the sample using the lab's microcantilever chips.

She also said that the use of microcantilever-containing biochips, which are manufactured via established semiconductor techniques, should allow "batch production" of arrays that are more sensitive than competing technologies, such as quartz crystal resonators.

"Nanomechanical systems can exhibit extremely low mechanical compliances, translating biomolecular recognition events into measurable displacements," said Calleja. "Since the size of the biomolecules is comparable to one of the dimensions of the mechanical system — mainly the thickness [of the cantilevers] — the mechanical response is also highly sensitive to the properties of the adsorbed biomolecules."

Together with Mecwins, Calleja's lab is working on a TB assay that could be faster and more sensitive than existing kits on the market.

"Our goal is to speed up the detection, as compared to other technologies," said Calleja. "We can detect low concentrations of the DNA or RNA target in complex samples, and also use very small sample volumes as our devices are micro-nanofabricated. This is key to early detection of targets."

In addition to the TB assay development project, Calleja said that the researchers are also interested in applying the technology to detect gene mutations related to cancer, "as the technique has a high sensitivity, and not relying on a prior PCR or a labeling step would speed up the detection and lower the cost."

Calleja added that the approach would "suit perfectly" expression profiling assays, given the throughput achieved by Mecwins' system, but said that the groups are more interested in targeted applications, rather than general research, and that the platform is "not competing [with] sequencing technology."

'Necessary Toys'

Berlin-based Scienion, which specializes in arraying instruments and services, has many other collaborations besides the Bionanomechanics Lab partnership. In recent years, the company has ramped up its activity in the original equipment manufacturing market and has disclosed OEM deals with Genomica, Courtagen, Procognia, Maine Manufacturing, and, most recently, Anagnostics (BAN 12/11/2012).

CEO Holger Eickhoff told BioArray News this week that nanomechanical biosensors like those developed at the Bionanomechanics Lab in Madrid require "precise loading with capturing molecules," and that Scienion's technology delivers "low picoliter volumes that are sufficient to load these sensors."

The main challenge for Scienion has been to align the step of dispensing droplets to "these tiny sensors." He noted that the company has collaborated on multiple biosensor projects in recent years, where it "gathered experience with tiny sensing elements to be loaded with biomolecules," and that its instruments provide "all the necessary toys and tools required" to make such chips.

"We have very precise drive systems with micrometer precision and onboard cameras with horizontal and vertical orientation to precisely deposit a picoliter droplet with a functional biological molecule on a micrometer-size biosensor location of choice," said Eickhoff. He also said the process, while challenging, is scalable from R&D to full production for "all kinds of biosensors," including the Bionanomechanical Lab's microcantilevers.

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