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Sep 1, 2008 (Vol. 28, No. 15)

Delivery of Time-Lapsed Live-Cell Imaging

Honolulu-Based Nanopoint Develops a Series of cellTRAY Technology Solutions

  • Nanopoint began life as a spin-off from Oceanit Laboratories, a diversified science and engineering firm that counts among its inventions a test kit for ciguatera poisoning in fish and a nano surfboard.

    Cathy Owen, a Silicon Valley veteran, joined the founders of Nanopoint in 2004 as president to develop an ultrahigh resolution imaging system and commercialize a device the size of a microscope slide with microfluidic channels for growing and analyzing live cells. When technology invented at Oceanit shows market potential, a new company is spun off to commercialize it.

  • Advanced System

    In 2006, Nanopoint introduced cellTRAY, a live-cell biochip that contains thousands of etched wells and microfluidic channels. The chip, the size of a standard microscope slide, is fluidically closed, yet mechanically open, to allow live cells to be treated, manipulated, and viewed under a microscope.

    In June, Nanopoint launched the cellTRAY imaging system, model CT-2000. This product allows experiments to run on an inverted microscope for several days while capturing time-lapse images of live cells, according to Owen. “This is important if you want to do a time-lapse study and don’t want to spend all night in the lab,” she says.

    Nanopoint’s software controls the navigation, camera, shutter, filters, auto-focus, and microfluidics needed for imaging live cells. A 2,048 x 1,536 high-resolution scientific-grade color camera observes and documents images of individual cells isolated in cellTRAY microwells.

    “We can automatically capture 10 independent regions with 80 wells per region,” continues Owen. The time-lapse feature takes pictures all night long to document important events, such as stem cell differentiation. Researchers can view the recorded events the next day in the laboratory.

    “The CT-2000 system is appropriate for drug screening applications and stem cell and regenerative medicine work,” notes Owen.

  • Multistate Experiments

    Researchers use the system to watch nanoparticles carrying drug compounds, move through the microfluidic channels to cells that ingest them. Images confirm that the correct cells are tagged with nanoparticles. Then the scientists can observe whether the delivered drug produces a desired behavior in the cells. For these multi-step experiments, “a multi-stage delivery system with fluidics capability is very important,” says Owen.

    Other researchers monitor calcium uptake or the time it takes a drug candidate to kill cancer cells with the CT-2000. Additionally, researchers can run samples in parallel, allowing different doses of drugs to be compared or drugs to be tested on different cell types. Such early in-vitro toxicity tests could eliminate drug candidates that may cause side effects later in clinical trials or after a drug is marketed. For example, the once blockbuster painkiller Vioxx, was pulled from the market after it proved toxic to heart cells.

    The CT-2000 offers scientists at pharma and biotech companies “the ability to do more testing earlier in the drug discovery process than ever before,” claims Owen.

    The earlier CT-1000 system, the company’s first cellTRAY live cell imaging product, includes navigational, camera, shutter, and auto-focus software. However, it is a passive system without automated microfluidic capabilities that fits on standard microscopes.

    “It's good for short-term experiments that are under four hours in duration,” explains Owen, who adds that experiments involving RNA interference work well on the CT-1000 system because they generally do not need microfluidic flows.

  • Reducing Costs

    To make the switch from conducting experiments in microtiter plates, Nanopoint developed protocols for target sets of applications. Scaling down from larger volumes to microliter amounts is not a direct 1:1 conversion. The adjustment to smaller quantities of materials requires refinements of procedures.

    “The cost of developing drugs is astronomical,” says Owen, “so miniaturization helps to reduce costs.”

    Moreover, both the cellTray microfluidic slide and accompanying cellTray Dish, which looks like a rectangular Petri dish and holds the slides, are reusable. Laboratories that perform live cell experiments in Petri dishes “toss out sleeve after sleeve of plastic Petri dishes that make a significant volume of biomedical waste,” Owen continues.

    In contrast, cellTRAY dishes and slides are cleaned by sonication to remove particles, followed by autoclaving for sterilization. Notches in the cellTRAY Dish hold slides firmly in place while reagents are changed, and they can be stored in freezers without warping.

    Owen says that Nanopoint is passionate about nurturing future scientists and skilled workers for the growing biotechnology industry in Hawaii. To inspire middle and high school students to become more interested in science, Nanopoint sells a reasonably priced cellTRAY science kit.

    Students use a sterile toothpick to scrape the inside of their cheek, then deposit the scraping on a slide in the cellTRAY and stain it. Students observe their own live cells under a microscope. Teachers can reuse the cellTRAY dishes year after year to reduce costs. “We want to encourage young people to pursue scientific careers,” adds Owen.

    Nanopoint’s location in Hawaii makes it easy to attract Asian customers, investors, and distributors.

    “There is a large market for our technology in Asia,” she says, particularly for stem cell research. Through a network of Asian distributors, Nanopoint sells to government research labs, pharmaceutical companies, and university research centers in Korea, India, China, Japan, Singapore, and Taiwan.

    Hawaii offers some of the most generous investment tax credits in the nation. Local investors get 100% of their money back over five years as tax credits. Investors from out of state gain extra equity, because local investors trade equity for unused tax credits.

    This unique tax-credit program does much to help reduce investor risk. Hawaiian companies are eligible for fully refundable R&D credits as well.



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