SeptiCatchTM is a universal bacterial detection and identification system capable of detecting extremely small amounts of microbial DNA in a sample within 4 hours. It has three components: a reagent kit for performing chemical reactions, an analyzer for collecting data, and a software program that processes the data. To facilitate automation and ensure quality of the result, a blood sample collection kit (not shown here) is also planned.
How does it work?
SeptiCatchTM is a patent pending invention based on a time-tested technique known as PCR (polymerase chain reaction), a powerful invention that has been the workhorse of biotechnology for the past 30 years. It is basically a molecular Xerox machine that makes many copies of a DNA molecule so that an organism’s DNA in a sample can be detected by an instrument.
There are two ways to use PCR to detect a microbe in the blood. The first approach is called multiplexing PCR which uses a panel of specific probes (typically around 20 – 25 different probes) to detect a predetermined set of pathogens. This would be effective for diagnosis of a disease with known cause such as HIV, but it is not practical in the case of diseases like sepsis which can be caused by a wide array of pathogens. In this situation, a second approach called broad-range PCR which uses a universal probe would be ideal. For example, a probe targeting the 16S gene can virtually detect the presence of all pathogenic bacteria since all bacteria have the 16S gene.
Unfortunately, for sepsis, the level of detection sensitivity required is extremely high (~1 cfu/ml). At this level, source contaminants in conventional PCR reagents become a major issue. Because all commercially available PCR reagents are derived from bacterial sources, broad-range PCR will also pick up these contaminants at this sensitivity level, generating excessive false positive results which effectively render the result useless. This problem has been plaguing the field for nearly 20 years. Many people tried but none has come up with a satisfactory solution to overcome the reagent contamination problem, leading most people to abandon broad-range PCR and choose the less ideal multiplexing approach. Our inventors have now solved this problem with a novel process of performing the broad-range PCR by using a specially designed probe that is able to differentiate the contaminants from the non-contaminants. We call it the PE-PCR (primer-enhanced, or primer-extension) technology.
To go one step further, our inventors had also demonstrated for the first time that once a bacterial DNA has been detected by our PE-PCR reaction, we can directly determine the identity of the bacterium using a technique known as High-Resolution Melting Curve (HRM) analysis. This breakthrough eliminates the need to run a separate sequencing experiment to determine the identity of the bacterium, as it would have required in the conventional PCR process.
What are the benefits?
At the core of the SeptiCatchTM system is the breakthrough PE-PCR process that overcomes the source reagent contamination problem. Because PE-PCR is built on top of the convention process, it remains compatible with existing PCR instrumentation, therefore, allowing easy integration and adoption of the technology by clinical diagnostic labs. Moreover, the universal probe approach makes the chemistry relatively simple and inexpensive, yet, provides highly accurate and actionable diagnostic information in a timely manner. With further optimization, even faster result may be achieved. It has the potential to revolutionize how sepsis is managed and treated!