The recent outbreak of Ebola in West Africa underscores the urgent need for globally affordable tools to help fight infectious diseases. Among these, a method to rapidly and accurately identify the infectious pathogen is of particular importance.
In recent years, researchers have tried many ways to achieve easily portable and affordable molecular diagnostics solutions to help with curbing infectious diseases globally. Much effort has been put in developing novel microfluidics (e.g. DNA microarrays) technology to achieve miniaturization. Microfluidics biochips allow reactions of samples and diagnostics assay to take place in a small, disposable chip platform. However, these biochips still need to be “read out” by such instruments as fluorescent microscopes. And these instruments are often bulky and expensive.
For this reason, innovation in microfluidic biochips fell short of providing a complete solution for point of care diagnostics. Engineers at Anitoa (Palo Alto, CA. www.anitoa.com) took a different approach by focusing on technologies that enable compact instrumentation. Anitoa just introduced a CMOS bio-optical sensor that is highly integrated and low power. Combined with microfluidics technology, This CMOS biosensor can enable truly portable and affordable molecular diagnostic solutions.
Figure 1, Molecular tests (DNA, antibody) provide precise answers about the type of virus and bacteria behind infectious diseases
Anitoa recently announced the availability of the industry’s first 3e-6 lux ultra low-light CMOS Bio-optical sensor called ULS24. Anitoa’s single chip CMOS Bio-optical Sensor is capable of detecting 3e-6 (or 3×10-6) lux with a better than 13dB signal to noise ratio (SnR), consuming only 30mW. With this performance, CMOS Bio-optical Sensor can now replace the bulky and expensive PMTs (Photon Multiplier Tube) and cooled CCDs widely used today in molecular diagnostic instruments, which sense molecular reactions using fluorescence or chemiluminescence signaling principle.
Anitoa’s ultra low-light CMOS biosensor enables the realization of a wide range of low-cost and portable medical or scientific instrument. A field-portable Nucleic Acid Test (NAT) system that can precisely identify infectious pathogens is just an example. Such DNA test instrument solution can be deployed in the field and allows physicians to respond timely to potential epidemic diseases globally by prescribing life-saving treatments such as targeted antibiotics or anti-viral drugs on the site.
CMOS biosensor enables portable qPCR
One of the most powerful methods to detect and quantify infectious pathogen is through Real Time Quantitative Polymerase Chain Reaction or qPCR. qPCR achieves sensitivity and specificity through combined amplification and real time detection. qPCR can cause target DNA strands be selectively replicated millions of times, with the help of a special enzyme called polymerase. As the target DNA being replicated, they bind with specially designed molecular probes that are labeled with fluorescence materials. A sensor would capture the fluorescent signal emitted from these probes as a way to monitor the reaction, and detect and quantify the target bacteria or virus DNA.
With the high sensitivity and signal-to-noise ratio of Anitoa’s CMOS biosensor, system designers can fully take advantage of microfluidics innovations to achieve total system miniaturization. Microfluidics uses very small reaction volume and densely packed reaction sites. This also leads to faster reaction time. Anitoa’s CMOS biosensor has needed fast integration time and imaging capability to take advantage of microfluidic systems. With this combination, engineers at Anitoa are in the process of building a palm-sized microfluidic qPCR system that will work with today’s off-the-shelf qPCR diagnostic assays (see Figure 2 for validation results).
In addition to small size and fast detection, ultra low light CMOS biosensor can also help achieving better diagnostic results. For example, ultra low light CMOS can help overcoming an issue called photo bleaching by using much lower dose of excitation light (using LED instead of laser) to generate fluorescence. Reduction of photo bleaching significantly improves assay repeatability, making diagnostic results more believable. (Link to full paper can be found at http://www.anitoa.com/docs/anitoa-whitepaper-l.pdf)