InSilixa has developed a unique technology to create high-performance biosensor arrays using state-of-the-art CMOS (complementary metal-oxide-semiconductor) manufacturing processes. The devices based on this technology are generally referred to as CMOS biochips and can identify multiple targets including nucleic acids (DNA or RNA), peptides, or metabolites, in a massively parallel fashion (102 to 108 biosensors per biochip). CMOS biochips are highly integrated and include not only the molecular detection elements, but also all the analog sensor interface, data converter, and digital signal processing (DSP) components. This integration means that they do not require a bulky reader, scanner, delicate optics, or sophisticated microfluidics like conventional diagnostic instruments today. A CMOS biochip is truly a bio-analysis instrument-on-a-chip.
As shown in this figure, our solution includes a CMOS chip manufactured at a high volume semiconductor wafer fabrication facility before being uniquely packaged to accommodate fluidics, sample interfacing, and digital input/output (I/O).
InSilixa’s team has been developing this technology for more than a decade and has established partnerships with the largest silicon foundries and semiconductor packaging companies in the world. The outcome of all these efforts is a high-performance bio-analysis product applicable to many areas of genomics and proteomics with cost efficiency, manufacturing scalability, and the robustness that one expects generally of consumer electronics devices.
One of the unique attributes of InSilixa’s CMOS biochips is the diverse functionality of their biosensor “pixels”, which are basically the elements within the densely packed arrays. As exemplified in the figure here, the pixels include a molecular detection element (e.g., oligonucleotide probes in DNA hybridization arrays, or ion-selective SAMs in sequence-by-synthesis arrays) on the surface, a dedicated transducer element (e.g., photodiode, or an active electrode), and an electronic sensor interface circuitry. Moreover, elements of a temperature control system are also placed inside every pixel to accurately adjust the temperature of the array from room temperature to 100°C.
Depending on the biological application, InSilixa can easily tailor every feature of the individual pixels to meet the assay. More than 10 generations of CMOS biochips have been designed, manufactured, and successfully tested so far.
From a system integration point of view, it is straightforward to adopt CMOS biochips for most genomic and proteomic diagnostic applications as they can accommodate both flow-through and closed-tube assays within a huge temperature range. Typical examples are NextGen sequence-by-synthesis array or nucleic acid amplification testing (NAAT) assays. The integrated sensors and packages are also by design “PCR-compatible” and can perform fast temperature cycling without seal breakage or bubble formation.
Independent of the application or the assay procedure, the data from every pixel can be acquired in real time with a programmable rate between 0.01 Hz to 50 Hz. These datasets are acquired in parallel using a standard serial peripheral interface (SPI) protocol and are analyzed using InSilixa’s signal processing and sequence identification software packages.