Until now, there was no good method to quickly analyze biological samples and detect unknown pathogens. Through our work with Ibis Biosciences, we have developed a device that uses DNA analysis to determine the unique genetic signature of any sample to reveal both recognized and previously undiscovered organisms.
The private sector now has access to the same pathogen detection technology available to the FBI.
A well designed diagnostic product can offer medical personnel and security professionals answers that could potentially save lives. Omnica and Ibis Biosciences have teamed up to create an important advancement in DNA technology that will have significant effects on the efficiency of medical and forensic teams worldwide. Because the technology has not been seen in the private sector, most laboratory professionals may not be aware of the progress Ibis Biosciences (a subsidiary of Abbott Molecular) has achieved in the field of DNA mass spectrometry, a type of DNA analysis.
Mass spectrometry was invented in the late 1800s. Faster analysis time, accuracy, and usability have been steadily improved upon, especially within the last twenty years. DNA has been used in forensic analysis since the early 1980s, and as game changing as it was for science two decades ago, it has reached a degree of speed and accuracy that could not have been imagined.
Even before 9/11 there was a heightened awareness of biological threats, and the big concern then, as it is now, was the time it took to culture and identify unknown agents. Culturing time could range from days to weeks, and there was the possibility that some hazards would not be identified at all. In any case, in the event of a crisis, time to react effectively could be significantly compromised.
Most people know that anthrax can be used as a bio weapon, but they don't realize that there are over 1,000 other biological agents known to be harmful to humans. The problem doctors, hospitals, the FBI, and others have had in the past is that, out of all of these possibilities, it was necessary to narrow their guesses to a handful before testing could begin. That meant that many times, within a given time constraint, the agent couldn't be identified at all. But with new technology introduced by Ibis, no narrowing-down is necessary: not only can their device identify any pathogen, it can also test for all known and newly-emergent pathogens. This is the breakthrough that will revolutionize the DNA-testing industry.
Early funding for this technology came from DARPA for bio weapons surveillance in 2000. The original Ibis mass spectrometry device, the Tiger 1, required four rooms of equipment. It was followed by the T5000 a much smaller (practically portable) unit than the Tiger 1, and is still in limited use in twenty-three laboratories, including the FBI lab at Quantico.
When Ibis went to work on development of the T5000 they hired us to help with the program. As a first step, the client briefed us on the chemistry steps critical to the system and gave us an outline of what they wanted to accomplish. Our assignment was to develop less expensive custom parts, and to consolidate and standardize the mechanical platform. As part of the development program we built some virtual instruments for feasibility testing which lead to some good results. One significant change we made was the solution for reducing the complex throughput methods then in place. We combined two robotic sample processors that were in the T5000 device into a more efficient single carousel-type system.
In 2008 Omnica was contracted to develop a completely new device.
This time around Ibis wanted to move it out of the research lab and into the hospital laboratory. All of the appropriate clinical and FDA regulated design controls would need to be in place so the device could be manufactured and sold in the IVD market. It meant that there would be a lot of emphasis placed on design for manufacture and quality systems requirements. Another necessity was compatibility with their existing technology. It also had to employ the same chemistry as the earlier T5000 model. Our team, under the direction of Ibis Biosciences, now owned by Abbott Molecular, was hired to perform all of the major design, engineering, and software development from the bottom up.
The result has been a much more efficient and highly automated model, the T6000, trade named Plex-ID. The way it works is based on the theory that every living organism has a unique DNA molecular mass profile. Therefore, specific biological identification is made possible by accurately measuring the mass of certain DNA segments in a given sample. In order to do this, the Plex-ID device requires DNA that has been treated in a process called PCR, which causes the DNA to unwind from its original double strand configuration into two single strands. That same process multiplies (called amplification) those single strands millions of times so they can be more easily detected in the analysis stage. The amplification stage takes four to six hours. The resulting amplified DNA is used in the Plex-ID.
First, the machine automatically desalts and purifies the sample containing the amplified DNA strand segments. The purified samples are aerosolized, given an electronic charge, and then passed through the onboard "time of flight" (TOF) mass spectrometer. The TOF analyzes the DNA strands, accurately calculates their mass profiles and compares them to a mass profile database of known pathogens. If the subject is not in the database, identification can be inferred because of genetic similarities.
The Plex-ID significantly reduces the time and sample throughput requirements that have been a part of DNA testing since the technology was first introduced. Bioagent accuracy is equivalent to current laboratory "gold standards", but instead of waiting days or weeks (or forever) for results, amplified biological samples used in the Plex-ID system can be identified in about 30 seconds.
Ron and Kevin discuss the carousel mechanism and how it accurately
determines its position when dispending reagents.
In addition to the obvious reasons for selecting Omnica for product development, our clients appreciate our unique perspective when engineering their projects. For example, Ibis welcomed our suggestion for a different way to install and service the mass spectrometer (TOF) into the finished Plex-ID. The custom-built TOF weighs 500 pounds, which is way too heavy for one person to lift without some type of mechanical assistance. Originally it was proposed that technicians who serviced and installed the tall and ungainly TOF would use hydraulic jacks to move it into place. It was to be a delicate and potentially hazardous 2-person operation to raise the cumbersome component sixteen inches and slide it into position. We knew there had to be a better way.
We spoke with the TOF manufacturer and requested that they modify the structure of the internal frame to offer some secure lift points and not flex as much when it was moved. We designed, and filed a patent application for, a foldable crane mechanism with an extendable boom that deploys from the sturdy internal aluminum structure of the T6000. A heavy duty motor operated with a pendant positioning controller drives chain-driven lift arms that are extended and attached to the integrated TOF lifting straps. It is now possible for one person to safely lift and move the heavy component into its intended position inside the Plex-ID device.
For this project, an integral component of our engineering service was to host
contract manufacturer visits, where we demonstrated and discussed the processes
and procedures for assembling all systems and subsystems.
The project had its challenges, even for our seasoned group. Some of them had to do with the exceptional scope of the program. The project was so extensive that we had to establish a unique protocol where each engineer followed a specific procedure for completing their assigned tasks. That information was sent directly to the client who received it and took responsibility to incorporate it into their output documentation files. It was a fully customized formal design and transfer process. We worked closely with the Ibis group in Carlsbad and the manufacturer to accomplish this part of our assignment as smoothly as possible.
We developed this system over a period of 2 years and the scope of the project was significantly modified over time. The changes in the program are evinced by the addition of a second computer, compressor, roughing pump, power supply, keyboard, a touch screen display, barcode reader and considerably more software development than we had originally planned.
We successfully implemented the requirements from our two customers, Ibis Biosciences and Abbott Molecular, and believe that we exceeded their expectations. The result is an award-winning and self-contained freestanding instrument that will supplement our national security, and initiate a positive effect in the medical services industry.
In 2009 the Plex-ID won two prestigious awards. The Wall Street Journal recognized the Plex-ID as the 2009 "Innovation of the Year" Gold award. The online magazine, The Scientist.com said the Plex-ID was one of "The ten most exciting tools to hit the life sciences in 2009".