Streaking ahead for microbiology

Robert Koch is remembered almost as much for the development of new methods of cultivating and staining bacteria as he is for his discovery that anthrax bacilli produce enduring endospores and identifying the bacteria that cause tuberculosis and cholera. Working with Walther Hesse, who developed agar as a culture medium, and Julius Richard Petri, of dish fame, at his laboratory at the Imperial Health Bureau in Berlin in the 1880s, Koch developed new methods of obtaining pure cultures and of staining bacteria to make them easily identifiable.

Not only did he get the Nobel Prize for Medicine for his work in 1905, but his methods are still pretty much the standard in preparing specimens in contemporary pathology laboratories, almost one hundred years after his death. The problem is, the traditional method of plating and streaking specimens is still a manual job and proves to be rather labour-intensive.

For John Glasson, chief scientist for clinical pathology at the Institute of Medical and Veterinary Science (IMVS) in Adelaide, that seemed rather curious. Having watched automation of routine laboratory methods free up medical scientists for more important work in most areas of clinical pathology, the fact that diagnostic microbiology was still a little hamstrung by tradition needed to change.

About five years ago, Glasson undertook a review of the potential solutions on the market and found there weren’t any, setting him to thinking about how the process could be automated. He took a few preliminary ideas to the IMVS executive and then met up with a young biomedical engineer called Lachlan Smith, who was doing PhD studies through the University of Adelaide’s Department of Pathology.

Together, Glasson and Smith came up with the idea for what is now MicroStreak, a robotic system using a patented streaking applicator that can potentially automate up to 90 per cent of what is now performed manually. MicroStreak, which will be marketed as PREVI Isola by diagnostics giant bioMerieux, was launched at the European Congress of Clinical Microbiology and Infectious Diseases in Spain in April, at the American Society of Microbiology meeting in Boston in May and at the Australian Society of Microbiology conference in Melbourne in July.

Glasson says he came up with the idea due to the increasing demands he could see in the area of diagnostic microbiology. “Some of the work has been increasing, particularly in microbiology, by five to 20 per cent a year,” he says. “And because it has been such a manual system, preparing specimens. The question was, why isn’t there automation available, as there is in chemistry and general clinical pathology? The automated streaker that we have now is the result of that.”

---PB--- How does it work?

The core idea of MicroStreak is based around a plastic, sterile, disposable applicator that functions like a comb or set of tines on a fork, Glasson says. “The specimen is presented to and deposited on the agar plates, and the comb is then put on top of the specimen and the plate spins,” he says. “It’s that spinning and the combing that actually does the same work as the conventional streaking method.”

The instrument is about the size of a small piano and can process about 180 plates an hour, far in excess of what humans can do at their most efficient. The system uses barcodes for identification, and each laboratory enters its protocols into the instrument’s memory.

“When the machine sees a particular type of specimen it can work out which agar plates to select for that protocol,” Glasson says. “That is controlled by computer so that once all of the information is put in it is there forever and you can just walk away from it.

“For instance, if you are looking for salmonella or campylobacter, the machine is engineered so that it can manage any of those plates. It is up to the microbiologist in charge to select what plates to use. They program the machine.”

Glasson has published results in the Journal of Clinical Microbiology that show the automated system achieves superior results to the manual method. “We’ve done a lot of work on multi drug-resistant bacteria and have done some of that here in our clinical trials. The machine was quite adequate – in fact it was better than the manual method in selecting pathogenic bacteria.”

While Glasson is the brains behind the idea, the robotic technology has been developed in association with two Melbourne companies: specialist medical design and engineering company Invetech and biomedical equipment manufacturing company Leica Biosystems, formerly known as Vision Biosystems.

But the work of getting it to market has been undertaken by listed biotech LabTech Systems, an Adelaide company first set up to commercialise a monoclonal antibody technology from the Royal Adelaide Hospital. LabTech Systems is led by Lusia Guthrie, a former laboratory scientist with many years of experience in operations and commercialisation.

“LabTech Systems first took an option on the technology when we found out about it and we raised the money for the proof of concept stage and then raised the money to take it forward since then,” Guthrie says. “Because this technology and the other one we had were quite different – it’s an oncology product – we spun that out and concentrated on MicroStreak.”

(The spun-out company, Oncaidia, is developing a monoclonal antibody called Apomab for oncology applications. It targets the La protein, which is significantly overexpressed in cancer cells.)

“We originally raised the money by doing a small listing on the Newcastle Stock Exchange, and while listing on the NSX is not that dramatic, it helped us to put into place all the corporate governance procedures, all the accounting and all of the legal that are needed to get a public company going,” Guthrie says.

“Then when we decided we’d go for broke and needed to raise millions rather than hundreds of thousands of dollars.

“So we listed on the ASX and we raised an additional $4 million to secure the project. At the time we were looking for a distributor as we knew we had to think globally – we had to be bold and think globally – because we’d never recover the development costs just in Australia.”

This is when bioMerieux came in. The French company is one of the largest diagnostic equipment distributors in the world, and fortunately for LabTech Systems and the MicroStreak, it was scouring the globe for something just like this. The instrument will be sold under the bioMerieux trademark and will be called the PREVI Isola, part of bioMerieux’s new portfolio of microbiology laboratory automation platforms. This portfolio also includes the PREVI Color Gram, a new automated staining technology, and the UF-1000i, a urinary screening tool that allows laboratory technicians to accurately detect and enumerate the bacteria and particles present in urine specimens.

LabTech Systems signed an exclusive license agreement with bioMérieux in April 2007 and received $3,243,000 upon signing. The company has since received a further $1,690,000 licence fee payment and is entitled to receive up to a total of approximately $11.2 million in licence payments.

Not bad for a small Adelaide company that has had to keep the idea a bit quiet for the last few years in fear of someone else beating them to the punch. “We spent four years being terrified that we were either really really smart or really stupid,” Guthrie says. “Now, we’d like to see the instrument in every microbiology lab out there.

“When you see the system, it is so simple, so easy to understand the applications. We did some focus groups with lab managers who knew the benefits of automation in clinical chemistry and other areas of clinical pathology, but they weren’t too sure about clinical microbiology.

“What is interesting about our story is that we’ve got an inventor who knows everything about automation in laboratories but nothing about designing instruments, and we’ve worked with an automation expert who knows nothing about microbiology, but instead of having someone who is second guessing what is happening in a laboratory, we have an approach that hasn’t been hamstrung by any preconceived ideas. We let people go with free-thinking ideas, always guided by what the problem is in the laboratory and what the customer would expect to see in a product.”