September 15, 2011 (Vol. 31, No. 16)

Many companies exhibiting at the “European Laboratory Automation” (ELA) congress were hesitant to make major announcements or unveil new products at a new conference taking place right on the heels of “BIO2011”. Nonetheless, several new offerings caught GEN’s eye.

TALEN-ted Molecular Scissors

Cellectis bioresearch touted its new service for engineering customized genetic modifications. Earlier this year the company obtained exclusive rights to transcription activator-like effector nucleases (TALENs®)—a dimeric protein fusion of a highly specific DNA binding recognition sequence with an endonuclease—which can be used to make precise double-stranded breaks.

Because of its straightforward cypher—the two amino acid repeat variable di-residue (RVD) of a 33–35 amino acid repeat domain recognizes a unique nucleotide—it’s expected that TALENs can be made to target a wide variety of sequences.

The double-stranded breaks created by TALENs have been used to disrupt genes by nonhomologous end joining as well as to insert transgenes or introduce precise gene modifications (in the presence of a template) by homologous recombination.

Lars Knoch, Ph.D., Cellectis bioresearch’s Central European sales manager, sees TALENs as the “next generation” of molecular scissors—a field that currently includes zinc finger-nucleases and meganucleases.

TALENs allow for customized gene modifications, according to Cellectis bioresearch. The technology makes double-stranded breaks to disrupt genes, insert transgenes, or introduce gene alterations. The company sees TALENs as the next-generation of molecular scissors, joining zinc-finger nucleases and meganucleases.

Toxic Animal Farm

In his 10 years in pharmaceutical research, Steven Trim realized how difficult it was to source crude animal venoms and toxins in the U.K. and Europe. So he founded Venomtech—which houses a host of snakes, insects, scorpions, spiders, and other arthropods—to do just that.

Venoms contain a variety of different carbohydrates, enzymes, peptides, and nucleotides that, singly or in concert, can have a profound effect on physiology—as analgesics, antimicrobials, or anticancer agents, for example. The crude venoms themselves, as natural products, are free from IP constraints.

Custom volumes of individual venoms are sold frozen in low protein-binding vials rather than lyophilized, which could potentially lead to some loss and expose personnel to potentially toxic dusts. Custom and off-the-shelf 96-well Venom Discovery Arrays (VDA)—“with 32 snakes in triplicate, 48 tarantulas in duplicate, or 96 arthropods in singlet,” for example—are also available for screening, Trim said.

Because they contain complex mixtures—with the components of some species overlapping those of others—a VDA is a “naturally compressed hit-to-tool screening plate” with built-in redundancy to help identify the hit, he explained. In addition, natural selection has modified many of the components, allowing for even more ways to probe the potential structure-activity relationship and determine selectivity.

Venomtech provides crude venom and hemo-lymph from many arthropods including the orange baboon tarantula.

Pray for a Preddator

Redd&Whyte worked with pharma to develop a line of small, versatile dispensers for the research community, which co-founders Martyn Hanlon and Roger Poole, M.D., were happily showing off at ELA. “We knew industry needed this equipment,” said commercial director Hanlon.

“The Preddators can dispense any fluid from DMSO to oil, in any dispense pattern,” he added, with the ability to mete out detergents and surfactants with virtually no foaming. “They will even do grease and cells.” Hanlon boasted that the instruments can fill 300 1,536-well plates with the worst, stickiest protein before the tips begin to clog.

These modular, upgradable instruments come preloaded with more than 100 programs in their flash memory, and can also be controlled by a PC or integrated into an automated platform, enabling them to fill any plate up to 3,456 wells, as well as dispense to custom-patterned plates and surfaces.

Preddator’s open-architecture software makes it useful for applications as diverse as PCR, multispotting arrays, protein crystallography, and dispensing gels. Solenoid valves dispense volumes from 20 nL to 200 µL. It comes in one- and four-channel versions, with the four-channel Preddator S4 capable of filling a 384-well plate with 1 µL in 15 seconds, and a 1,536-well plate in a minute, according to the firm.

Thermal Cycler

Among the products Thermo Fisher Scientific  had on display was the diminutive (and “green”) Piko thermal cycler, available in two block configurations. The 24-well block can handle standard low profile single tubes, 8-tube strips, and 24-well Piko PCR plates, while the 96-well block is designed to use 96-well Piko plates.

Piko plate wells are ¼ the size of conventional PCR microplate wells. This, combined with the plastics’ faster heat transfer, allows the Piko thermal cycler to complete 30 PCR cycles in just 15 minutes, said Hilkka Sarapisto, commercial product manager for sample preparation and analysis, Europe and emerging markets. And this, the firm claims, results in a huge savings in energy cost of operation, reagent usage, and plastics consumption.

Though Sarapisto pointed out that the machine is not designed for high-throughput screening, the Piko plates utilize industry standards for well spacing and sample capacity, making them compatible with a variety of multichannel pipettors, reagent dispensers, and liquid-handling systems.

Also touted was Thermo’s Arktik thermal cycler, with interchangeable blocks allowing it to be transformed between a 96-well and a 386-well instrument. It can also be operated as two independent 48-well instruments, simultaneously utilizing different programs, Sarapisto noted.

Although Thermo Fisher Scientific’s Piko thermal cycler is only about half the size of a typical thermal cycler, the firm claims that performance is not compromised and that a PCR protocol can be completed in under 15 minutes. The Piko instrument is suitable for both conventional and fast PCR applications, Thermo says.

Go For the Gold

IBIS Technologies showed off its IBIS MX96 surface plasmon resonance (SPR) system for label-free imaging of biomolecular interactions. The instrument is designed to work in conjunction with the company’s Continuous Flow Microspotter (CFM), which uses a network of microchannels to print arrays on the surface of sensors from dilute 70 µL ligand samples, said Richard Schasfoort, Ph.D., CSO.

Sensor chips with standard or custom dimensions are available from the company, with surfaces ranging from bare gold to a variety of capture surfaces and activation chemistries. Typical applications range from kinetic rate and affinity constant measurements of antigen-antibody pairs, to antibody selectivity testing and even identification of individual epitopes involved in antibody binding.

The latest system developments allow for a higher throughput and at least 20-fold greater sensitivity than IBIS’ earlier platforms, said Dr. Schasfoort. By exploiting its multiplexing capabilities, for example, 10,000 sensorgrams can be obtained overnight, which affords significant productivity increases.

This multiplexing can be used to measure a given interaction using multiple different ligand densities and analyte concentrations in a single experiment, and the software can calculate highly accurate affinity constants in a way that avoids inaccuracies typically imposed by ligand re-binding effects as encountered with conventional platforms. For customers who choose not to purchase their own system, IBIS also provides its services as a CRO.

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