When asked her opinion about emerging technology in the positioning and nanopositioning equipment industry, Jenice Con Foo, a marketing representative at Mad City Labs Inc. in Madison, Wis., said that the company has seen a rapidly increasing demand within biotechnology and the life sciences for ultrahigh-precision imaging systems. The introduction of highly precise piezo Z-axis stages has been one of the key enabling components for high-speed confocal imaging and image reconstruction techniques, she added.
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The development of focus-correction devices, using a variety of techniques, is another exciting area contributing to higher-precision instrumentation devices, Con Foo said. The explosion of interest in nanoscale biotechniques has been a stimulus for the company, which has incorporated advice from users into its microscopy-related piezo stages – such as the need for slimmer profiles and larger apertures to accommodate biological media. Mad City Labs manufactures flexure-based nanopositioning systems that achieve subnanometer positioning resolution. Its product line covers the full spectrum of nanopositioning capabilities while specializing in multiaxis stages for high-speed optical microscopy imaging. The company uses 3-D computer-aided design and finite element analysis to produce nanopositioners that combine long range of motion with high linearity, orthogonality and stability.
Highly precise positioning products for the biotechnology and microscopy markets are offered by Mad City Labs Inc. Shown from left to right are a low-profile Nano-Bio series two-axis nanopositioning system, a Nano-View/M series fully integrated positioning system and a Nano-F series objective lens positioner. Photo courtesy of Mad City Labs Inc.
Con Foo explained that the major applications for nanopositioning and precision motion equipment lie in optical trapping/tweezers, particle tracking for biomolecules, reconstructive imaging and super-resolution microscopy techniques such as stochastic optical reconstruction microscopy, stimulated emission depletion and photoactivated localization microscopy. She added that, although some of these techniques are still in their infancy, there is optimism that they will lead to better analytical instruments and eventually better diagnostic tools.
System integration – making all the hardware and software talk to one another – is one of the biggest challenges that the company’s customers face, Con Foo said. Post image acquisition software and modeling are other areas of interest, she noted. “The further you go into the nanoworld, the more you have to consider other factors that could inhibit your ability to look at the nanometer scale,” she added, giving as an example the need to understand the thermal characteristics of the instruments and the laboratory. In conventional optical microscopy, thermal gradients on the instrument or even the temperature control of a laboratory haven’t been serious matters, but at the nanometer scale, even a small change in temperature is significant, Con Foo said.
Concerning the economic downturn, she said that, in her segment of the market, she is seeing continued growth and interest from both the commercial and research sectors. Part of the reason is that government and industrial customers are still investing in precision motion technology. The industry view is to continue development of instruments and techniques so that when the economy turns around, the technology will be ready for the market.
The biggest trend likely to bolster the industry in upcoming years is the demand for all types of nanoscale information, whether in conventional markets such as semiconductors, or in the emerging fields of medical imaging and microscopy.
“Mad City Labs employs proprietary PicoQ sensor technology, which outperforms capacitive sensors, yielding products with ultralow-precision noise,” Con Foo said. Among the company’s products are the Nano-LPS 20-mm-high three-axis piezo positioning stage, which travels up to 300 μm per axis with subnanometer precision, and the Nano-PDQ multiaxis nanopositioners with up to 75 μm of motion per axis – designed for applications such as particle tracking, where milli-second response times are required.
Some motion control products for biophotonics applications: a piezo flexure nanofocusing device for Z-stack imaging (right); a piezo well-plate scanner for drug discovery applications (foreground); and a low-profile X-Y microscopy stage (background) that uses autolocking piezoceramic motors for fast response and long-term stability. Photo courtesy of PI (Physik Instrumente) LP.
Stefan Vorndran, director of corporate product marketing and communications, and Scott Jordan, director of nanopositioning technologies, both at PI (Physik Instrumente) LP in Auburn, Mass., said that the industry is early in the era of motors built on something other than magnetism. Piezoceramic motors have been around for decades, but only recently have breakthroughs in materials science and control technology enabled them to be used in a wider range of applications. Their benefits in terms of speed, responsiveness, stability and size are remarkable, and they are enabling photonics applications such as optical tweezers (where long-travel resonant piezomotor stages provide the nanoscale ability essential to the task), they said.
PIFOC closed-loop piezoelectric nanofocusing devices from PI (Physik Instrumente) LP are used for Z-stack imaging in bioresearch and can provide 3-D images 10 times faster than conventional motor drives, according to the company. Photo courtesy of PI (Physik Instrumente) LP.
Nanopositioning is essential for a variety of microscopy applications and implementations, according to Vorndran and Jordan. For example, the field of single-molecule biophysics relies on subnanometer positioning equipment to optically sense and even manipulate the activities of the molecules, while the field of super-resolution microscopy is based on piezo nanopositioning stages and capacitive feedback technology that is free of Johnson noise, also known as thermal noise, providing a step forward in sensing resolution and stability. The field of scanned microassays, which is the foundation for applications such as drug discovery and clinical genetic testing, employs a diverse selection of automated motorized and piezo mechanisms for scanning and focusing.
New controllers for nanopositioning stages and actuators. Photo courtesy of PI (Physik Instrumente) LP.
Vorndran and Jordan noted that education and marketing are among the larger challenges facing the positioning equipment industry. Many of the users in biology and medical applications are new to motion, automation and dynamic considerations. “Selecting the right nanopositioning system for the task is not always easy because sometimes vendors’ specifications seem to be based more on fantasy than physics,” Vorndran said, adding that extensive test and metrology equipment and training are required to verify precision on a nanometric and millisecond scale and below.
Currently, motion capabilities have outstripped metrology’s progress, and progress in sensor technology is the next pacing item for the industry, according to the PI representatives. New control techniques, better and faster communications interfacing, and sophisticated software to make the extensive power usable on a human scale are all required to take advantage of the emerging performance in the technology, Vorndran and Jordan said. They added that development in vibration isolation needs to keep pace with advances in applications, noting that a positioning system with subnanometer capabilities would not be compatible with an ambient environment that has vibrational amplitudes in the micron range.
Although important markets for positioning equipment, such as the semiconductor and telecommunications sectors, have been hard hit in the economic slowdown, there is still a lot going on in areas such as the life sciences, said Vorndran and Jordan. Some positioning technologies, such as long-travel resonant ceramic motors, open new possibilities. For example, a motion device driven by a conventional motor cannot be operated in an MRI application, but a ceramic piezo-motor is unaffected by magnetic fields and produces none of its own, so that presents tantalizing new possibilities to innovators in that field, they said.
Speed and synchronization
Industry players who can satisfy the universal hunger for speed will thrive, the PI representatives said. Motion applications will require faster throughput and tight synchronization – time is money. The demand is for motion controllers based on real-time interfaces and advanced control algorithms to synchronize commanded motion with execution; and for software architecture to help customers get to productivity sooner by letting them switch hardware and upgrade to new interfaces without rewriting the code.
The PL-200 slide loader is an advanced system for automatic slide handling in a variety of microscope applications. Photo courtesy of Prior Scientific Inc.
Along with other developments, PI is switching to a new generation of 24-bit-resolution nanopositioning stage controllers that will permit 60-pm command resolution even on the latest-generation long-travel piezo nanopositioning stages (1-mm or 1000-μm motion), like the company’s P-628 closed-loop multiaxis positioners.
Automated slide handling
Thomas Freda, president of Prior Scientific Inc. based in Rockland, Mass., said that the company’s new PL-200 slide loader for upright microscopes can load up to 200 slides unattended and interfaces with its highest-precision motorized stages. Precision stages with closed-loop feedback [and] with 50-nm-resolution scales are also a very exciting technology development, he added. Also, the company’s flattop inverted stages can be combined with these precision linear scales to provide high-precision movement.
Freda said that Prior Scientific will be introducing a new controller that will be modular in design and that will combine control of a stage, focus drive, multiple filter wheels, multiple shutters and piezo Z-stages, and have additional axes available for products in development.
The ProScan II high-precision H117 flattop stage complete with a 200-μm nanopositioning piezo Z-stage. Photo courtesy of Prior Scientific Inc.
Live-cell time-lapse imaging, high-speed scanning of well plates and scanning of slides for virtual slide storage are among the major photonics-related applications for positioning and micropositioning equipment in the medical and life sciences sectors, Freda said. The industry is challenged by the need for high-speed/high-acceleration movement with fast settle times, optical systems to minimize the thermal effects during scanning, and software to easily and seamlessly integrate all of the optical accessories, Freda said, adding that researchers are always looking for better repeatability in their time-lapse experiments, which pushes manufacturers to look for ways to improve this feature.
Freda said that what used to be the most problematic was assuring that individual components would function as an integrated system. He added that having the components function well as a system now requires looking at the environment in which the movements, measurements and study are to be completed. As an example, he said that researchers at the company are working in the single-molecule realm using Förster resonance energy transfer and are performing investigations at the nanometer level. He said that the real challenge is to be able to combat or mediate to an extent the external factors, such as room temperature and lower-frequency vibrations, that can wreak havoc in measuring small-scale incremental changes.
The positioning equipment industry overall has slowed somewhat because of the economic downturn, but that it is somewhat insulated because of government funding.