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Comparison of i-Diagnostics with Alternative Technologies
Prompted by the terrorist attacks on September 11, 2001 and the anthrax letters a week after, the U.S. government spent over $100 billion on biodefense . As a result, no analytical method has been left unexplored for molecular diagnostics. In 2014, The DOD performed an exhaustive survey of molecular diagnostic methods , ranking an earlier prototype of i-Diagnostics highly for both biological and chemical detection. To date, we believe i-Diagnostics holds a unique combination of features that keeps the technology unrivaled.
Why is i-Diagnostics so uniquely advantageous? The answer lies in the phenomena of Total Internal Reflection and the Evanescent Wave, the main actors in Total Internal Reflection Flourescence (TIRF), the underlying technology of i-Diagnostics. These phenomena provide exceptional surface selectivity and enable TIRF with the ultimate limit of detection - down to single molecules. TIRF is capable of detecting a multitude of single molecules of different classes simultaneously, a feature not found in any other technology. Additionally, since TIRF detects fluorescence only from a sub-micron layer next to the surface, minimal-to-no sample preparation is necessary. Whole blood and other complex biological fluids can be analyzed and the results can be obtained in a matter of minutes. This technology, which is supersensitive, accurate and rapid, can be downsized to an inexpensive handheld device for home use. The projected cost of the i-Diagnostics device is $400, while disposable cartridges are anticipated to cost $1-10. We are not aware of other technology that could be as sensitive, accurate, and rapid, can detect all four major classes of biomarkers, and yet be affordable.
In the area of diagnostics, there is a consensus that an accurate diagnosis requires the simultaneous detection of several biomarkers, provided that the occurrence of those markers is not correlated. Such markers are called orthogonal, they are independent on each other. Typically, for a single biomarker, the rate of false positive responses is 10% or greater. Assuming that this rate is 10%, for a panel of two orthogonal markers this rate decreases to 1%; for 3 markers, to 0.1%, and so on. i-Diagnostics is capable of detecting up to 40,000 molecular markers in parallel. However, in most practical applications, detecting more than 20 markers is seldom necessary.
1. PCAST Letter to U.S.President (PCAST - President’s Council of Advisors on Science and Technology), “Action needed to protect against biological attack,” November 2016. https://obamawhitehouse.archives.gov/blog/2016/11/15/pcast-letterpresident-action-needed-protect-against-biological-attack. Cooper J, “Bioterrorism and the Fermi Paradox,” International Journal of Astrobiology, vol. 12, no. 2, pp. 144–148, 2013.
2. Emanuel P, Caples M, Global CBRN Detector Market Survey, 2013, DOD, Joint Program Executive Office for Chemical and Biological Defense. 250 MB pdf file downloaded on May 1, 2015 from URL: http://www.cbrnlibrary.com/documents/Global%20CBRN%20Detector%20Market%20Survey_web.pdf; email your request to TIRF Labs at info@TIRF Labs.com to receive the Survey 250 MB pdf file via Dropbox or Google Drive.
3. Arlett JL, Myers EB, Roukes ML, Comparative advantages of mechanical biosensors. Nat Nanotechnol. 2011 Apr; 6(4):203-15.
Since DNA and RNA encode proteins and perform certain controlling functions, this class of markers is useful when detecting viral and bacterial pathogens and are advantageous for prognosis panels. However, because proteins are the molecules that manage live cells and tissues, and metabolites are products as a result of this management, an accurate diagnosis for many diseases and pathologies requires the detection of protein and metabolite markers. i-Diagnostics, as mentioned above, is capable of detecting all three classes; no alternative method covers more than two classes. Table compares i-Diagnostics with top alternative technologies.
The advantage of having minimal-to-no sample preparation is of paramount importance for rapid and accurate diagnostics. Many molecular markers, especially RNA, are not stable enough to endure the shipping and certain stages of sample preparation. As a result, useful informative markers are lost before the sample becomes available for measurements. i-Diagnostics is free from this disadvantage; it can detect unstable markers in situ or right after taking the sample.
Although a multitude of molecular diagnostic projects have been funded that resulted in useful technologies, a solution for accurate diagnostics for home use is not within sight yet. As mentioned above, no other technology, except i-Diagnostics, possesses this unique set of advantageous features necessary for home use. The alternative technology closest to i-Diagnostics in accuracy and sensitivity is electro-chemi-luminescence (ECL). The i-Diagnostics platform supports the ECL method. However, ECL requires labor-intensive sample preparation and a sophisticated electrochemical system in addition to a photodetector, greatly driving up the cost.
In summary, amongst the broad spectrum of biodetection methods, we believe that i-Diagnostics demonstrates an unrivaled combination of technological advantages, including: (i) the low limit of detection and high sensitivity needed to detect virtually all clinically significant markers, (ii) the broad dynamic range, which covers the entire spectrum of biomarker concentrations that are clinically significant for diagnosis, (iii) the ability to simultaneously detect all three classes of biomarkers (e.g. proteins, DNA/RNA, and metabolites), (iv) the exceptional flexibility of the platform that permits the interfacing of bioassays and chemical assays for the detection of bioanalytes and chemical analytes of different classes. Currently, we are not aware of any other technology that could be as sensitive, accurate, and rapid, can detect all four major classes of biomarkers, and yet be affordable at the level of $400/device-reader and $1-10 for disposable test cartridges.