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Molecular iDiagnostics for Home Use
by TIRF Labs
Comparison of iDiagnostics with Alternative Technologies
After 9/11 followed by the anthrax letters attack, the US government spent over $100 billion on biodefense. No analytical method has been left unexplored for molecular diagnostics. However, only one stands superior to all of them. To the best of our knowledge, iDiagnostics is the only technology which is supersensitive, accurate and rapid, multiplexed along several major classes of molecular markers, and yet can be downsized to an inexpensive handheld device for home use. The projected cost of the iDiagnostics device is $100, and disposable cartridges are anticipated to cost $1-3. 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. If such technology, an alternative to iDiagnostics emerges in the future, we will incorporate it into the iDiagnostics platform.
Why is iDiagnostics so uniquely advantageous? The answer lies in the phenomena of Total Internal Reflection and the Evanescent Wave. 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. No other analytical technique demonstrates such a superior set of features.
There is a consensus in the area of diagnostics 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. iDiagnostics 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.
Since DNA and RNA encode proteins and perform certain controlling functions, these classes of markers are 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. iDiagnostics is capable of detecting all four classes; no alternative method covers more than two classes.
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. iDiagnostics is free from this disadvantage; it can detect unstable markers right after taking the sample.
Bill & Melinda Gates Foundation (Microsoft), Chan Zuckerberg Initiative (Facebook), The Brin Wojcicki Foundation (Google), and other members of The Giving Pledge have funded a multitude of molecular diagnostics projects that resulted in the development of useful technologies, e.g. 23andMe. However, a solution for accurate diagnostics for home use is not within sight yet. As mentioned above, no other technology, except iDiagnostics, possesses this unique set of advantageous features necessary for home use. The alternative technology closest to iDiagnostics in accuracy and sensitivity is electro-chemi-luminescence (ECL). However, ECL requires labor-intensive sample preparation and a sophisticated electrochemical system in addition to a photodetector, greatly driving up the cost.
There is an extensive amount of literature on molecular diagnostics, including review articles [e.g. 6: see comparison tables pp 26-28]. In 2013, the DOD issued a 663-page survey , which has overviewed most of the molecular diagnostics products developed by 2013. This survey ranked our classical TIRF array biosensors as one of the most promising devices for military applications. We performed further analysis from the standpoint of civil applications and compared iDiagnostics with alternative technologies that theoretically could be employed for home use. We found that iDiagnostics showed several superior 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 at least four 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.