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iDiagnostics - the handheld future of precision medicine; Single Molecule Detection, Single Cell Analysis,  Cell Membrane Studies, TIRF microscopy, TIRF accessories for fluorometers, TIRF biosensor instruments, Real-time TIRF microarrays, and more>>> visit  www.tirf-labs.com

Molecular iDiagnostics for Home Use

by TIRF Labs

www.tirf-labs.com

Mail: info@tirf-labs.com

Fig. 1. Photo and schematics of iDiagnostics.

Fig. 2. 3D-enhanced TIRF microarray in comparison with classical 2D microarray.

    3D

Turn your cellphone into an accurate, rapid, and yet inexpensive diagnostic device

Fig. 4 shows main components of the iDiagnostics ADK and uTIRF Biodetection Station and Fig. 5 - main stages of microarray printing, assaying and data acquisition and analysis.  The set of ADK and uTIRF station will be used by researchers, who are interested in interfacing their existing assays with iDiagnostics platform and who will be developing new assays and panels of assays. Before testing the panels of assays with iDiagnostics cartridges and cradles, the stages of assay development, validation, calibration and other development tasks will be implemented using uTIRF station. For these purposes uTIRF is equipped with open perfusion and closed flow chambers. There are several formats of open perfusion and closed chambers for different tasks. Open perfusion chambers are suitable for easy access to each individual spot of the panel. For more information about iDiagnostics ADK and uTIRF station  refer to ADK and uTIRF pdf brochures and contact TIRF Labs via email: info@tirf-labs.com.

 Although the uTIRF Biodetection Station is a brand new product by May 2018, several research groups worldwide have requested this new product along with iDiagnostics ADK for their studies. Distributing uTIRF-ADK and other iDiagnostics development tools, we will keep in mind that the ultimate goal of the iDiagnostics project is to create a decentralized precision diagnostics affordable for all. Fig. 1 shows an early prototype of iDiagnostics and disposable cartridges. In Phase 1, we plan to transform the first prototype into a robust iDiagnostics product well-suited for home use by minimally trained individuals, similar to pregnancy test strip.  In Phase 1 we will explore the possibility of including  a cellphone camera and a processor into the cradle in order to make iDiagnostics simpler and more user-friendly. By the middle of Phase 2 we will have a well-refined iDiagnostics product ready for manufacturing.

Despite its small size and low cost, iDiagnostics will be an analytical device as powerful as a bench-top laboratory instrument; it also will be used by medical doctors, first responders, clinical researchers, and other specialists. We anticipate that several months after we receive the necessary funds, a number of tests for laboratory use - including food safety, allergens in food, prostate cancer, and breast cancer - will be developed, validated, and used for research purposes in academic, government, and industrial research groups.  

The Goal of the iDiagnostics Project

The goal of this project is to provide accurate diagnostics for home use to every family on the globe. We envision a handheld device, called iDiagnostics, that uses a cellphone’s camera to measure the response of a real-time Total Internal Reflection Fluorescence (TIRF) microarray. Unlike alternative methods that detect only one class of biomarkers and, therefore, are inaccurate, TIRF microarrays measure the concentrations of several classes of biomarkers, including proteins, nucleic acids, and metabolites.  iDiagnostics’ unsurpassed accuracy comes from its ability to detect these biomarkers simultaneously with minimal-to-no sample preparation. Despite all of these seemingly complex things, iDiagnostics is inexpensive and user-friendly for home use by minimally trained individuals, similar to the pregnancy test strip.

As of now, the practice of medicine in the US is extremely imprecise; documented medical errors represent the third-greatest cause of death in the US  [1, 2]. Accurate and affordable technology such as iDiagnostics will dramatically reduce the number of medical errors. Additionally, iDiagnostics will improve humanity’s chances for survival in the long run. Global security experts concur that naturally occurring pandemics already present a major threat, while man-made synthetic pathogens may pose an even greater risk of the complete self-eradication of mankind [3, 4]. To minimize these risks, the world needs a device such as iDiagnostics. If accurate and rapid diagnostic devices become available not only to first responders and healthcare professionals, but to everyone, then every risk, from medical errors to pathogenic catastrophe, can be minimized.

Fig. 4:  iDiagnostics Application Development Kit (ADK) and uTIRF Biodetection Station . For more information click here and here

TIRF Labs Team

The following scientists and engineers have contributed significantly to the development of TIRF microarray and iDiagnostics technologies: Luis Vaca, Ph.D.; Vladimir Omelyanenko, Ph.D.; Angelica Zepeda, Ph.D.; Alicia Sampieri, Ph.D.; Philip Oldham, Ph.D.; W. William Wilson, Ph.D.; Theodore Winger, Ph.D.; David Sachs, M.S.; Hardie Johnson, B.A.; David Landis, Ph.D.; Ryan Sherry, M.S.; Tyson Weiss, B.A.; Zhanna Brotsman, M.S., Grant Leonhard, Timothy Pike, and Alexander Asanov, Ph.D.


Personal Statement of Lead Scientist

   I, Dr. Alexander Asanov, believe that I am well-suited to lead Phase 1 of the iDiagnostics project. This project logically builds upon my prior work. In 1999-2014, I served as Principal Investigator on several BAA and SBIR grants, awarded by NIH and HSARPA. I assembled and led a team of extraordinary talented and productive scientists and engineers, who have developed a family of innovative TIRF instruments for molecular diagnostics and analysis of biomolecular interactions. My colleagues and I have pioneered several ground breaking discoveries and accumulated unique experience in using the TIRF technique and other analytical methods for life science applications.  I have a broad background in spectroscopy, electrochemistry, surface chemistry, molecular biology, cell biology, nanoengineering, mechanical engineering, and optical engineering, which are key areas for this project. Each of our prior projects resulted in the development of useful TIRF devices and instruments. Our customers from academic and pharmaceutical research groups have generated unique research data using our products, and have published articles in leading scientific journals. I have a record of successful R&D projects in the area of molecular diagnostics and believe that my prior experiences have prepared me well to lead the proposed project.

I am a naturalized U.S. citizen. In 1994, I immigrated from Russia. On my  24th year in the U.S, I feel that I am more American than Russian. My second Motherland recognized my accomplishments and rewarded me more than I could have dreamt of in Russia. I want to give back to society and believe that the development of iDiagnostics is the way, in which I can demonstrate my gratitude to America and the world. Although I have successfully managed all scientific, administrative, financial, and human resources aspects of our prior projects, during Phase 2  of the iDiagnostics project I intend to step down from the position of Chief Executive Officer to a position of Chief Scientific Officer. Respectively, in Phase 1  we will be looking for a candidate for CEO position, whose perception of the goal and the spirit of the iDiagnostics project would be close to ours.

Disclaimer

Neither human subjects nor laboratory animals are involved in this project. Genetically modified organisms and biologically hazardous materials are also not involved. Our collaborators, who do perform regulated studies, carefully comply with the respective government protocols and rules.


The field of lifesciences, in general, and the area of molecular biology, in particular, operates with powerful technologies that have strong potential for improving quality of our life. However, these powerful tools, if used improperly, can cause adverse effects.  We believe that scientists should be responsible for results of their studies. It is our company policy and responsibility of our workers to foresee possible adverse effects of our studies and adhere to the highest ethical standards to avoid possible adverse effects. We do not develop and do not support the development of controversial biological applications.  


Compliance with FDA Guidance

TIRF Labs complies with the U.S. Food and Drug Administration guidance, including the following:

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/PostmarketRequirements/QualitySystemsRegulations/

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/default.htm


The Software guidance documents http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm089543.htm

http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm126955.pdf


Design Considerations for Devices Intended for Home Use

http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM331681.pdf


Guidance for Molecular Diagnostic Instruments with Combined Diagnostic and Research Functions

http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM346553.pdf


Copyright Credits

We are grateful to the National Institutes of Health, Mr. Michael Astrachan - XVIVO Scientific Animation, Genome British Columbia, The Howard Hughes Medical Institute, and Dr. David Goodsell, The Scripps Research Institute, for their kind permissions to use their videos and images.


Risks and challenges

TIRF Labs has been working on molecular diagnostics for the last fourteen years and has created a family of TIRF instruments, including bench-top, portable, and handheld TIRF biosensors. We have assembled a group of scientists and engineers with vast experience in all relevant fields. However, a project of such scale as iDiagnostics involves new risks. To mitigate the risks of transition to clinical analyses, we are offering to the biodetection community uTIRF biodetection station and iDiagnostics Application Development Kits (ADK). uTIRF-ADK will involve a number of diagnostics research groups with their own networks, which will facilitate the entering of iDiagnostics into the conservative area of clinical analyses. The research and development of uTIRF and iDiagnostics have worked, and the prototyping and low-volume manufacturing of these products has been done. Now, a group of risks will be associated with the transition from low-volume manufacturing to volume production. To mitigate these risks, we are establishing parallel contacts with alternative manufacturing partners and collaborators to assure multiple possible channels for production. If a setback does arise in one of the channels, we will use an alternative channel. iDiagnostics is a sophisticated technology. We are using a number of unique methods and production technologies. We believe that we are able to foresee and minimize risks associated with these methods in order to deliver uTIRF and iDiagnostics ADK to our customers with full satisfaction. Keeping our existing and prospective collaborators and customers updated about our progress and receiving feedback from them is our priority.

How iDiagnostics Was Born

iDiagnostics is the result of an 11-year effort by TIRF Labs’ group of scientists and engineers. We have received $4.3 million in grants from the U.S. government and have developed a super-sensitive technology - 3D-enhanced TIRF microarrays. As mentioned above, TIRF is an exceptionally sensitive method capable of detecting biological particles down to single molecules. Fig. 6 shows our progress in the development of TIRF array biosensors, which spanned from large bench-top instruments created in 2005, through portable sensors produced in 2009, to small handheld devices built in 2011. In 2013, we discovered that silk fibroin enhances the fluorescence of TIRF microarrays so that we can use a cellphone camera instead of expensive cameras. This patent-pending discovery has been incorporated into iDiagnostics. In Phase 1 of the project iDiagnostics will migrate back to the handheld configuration, in which the cradle will be equipped with its own low light camera and a microcomputer. This turn will add little to the cost of the cradle, and will allow for avoiding several issues related to the use of cellphone software and to alignment of different cellphones with the cartridge.

Fig. 6. Downsizing TIRF microarray biosensors.

iDiagnostics Applications

Future applications for iDiagnostics will include tests for the diagnosis and prognosis of cancer, cardio-vascular diseases, Alzheimer's disease (and other neurological disorders), longevity studies, diagnosing of influenza, Ebola, HIV/AIDS, Zika, STDs (and other infectious diseases), food and water safety, biodefense, and forensic, environmental, military, and agricultural analyses. We believe that many routine analyses of blood, urine and other bodily fluids that currently are performed in clinical labs, will migrate to iDiagnostics, because of the convenience of home use tests. Along with the main goal of home use, family doctors, cardiologists, dentists, first responders, pharmaceutical companies, food safety, agriculture, and environment protection specialists have expressed their interest in using iDiagnostics for their applications. There are thousands of new applications that can be developed for the iDiagnostics platform. It is too difficult, if not impossible, for a single company to develop all of these numerous applications. Therefore, we invite other research groups worldwide to join our virtual team to interface their existing tests and develop new applications with the iDiagnostics platform.

To facilitate these efforts, we are offering the uTIRF Biodetection Station and iDiagnostics Application Development Kit (ADK), as mentioned above. We anticipate a large demand for uTIRF-ADK, because there are tens of thousands of research groups worldwide that develop diagnostic assays, discover and validate molecular markers, and investigate the molecular mechanisms of related biological processes. These research applications do not need FDA approvals. However, they will naturally pave the road  for medical use of iDiagnostics.

In our laboratory in North Carolina, we are developing diagnostic and prognostic tests for prostate cancer. We have developed iDiagnostics tests for food safety and detecting allergens in food. Our long-term collaborator Dr. Vaca from the Institute of Cellular Physiology at UNAM and his group are developing preemptive diagnostic tests for Alzheimer's disease and hepatitis C. His colleagues from other research groups will develop tests for pancreatic and colon cancer. Dr. Dong from Washington State University is developing tests for cardiovascular diseases. The Laboratory of Molecular Virology at the Food and Drug Administration have expressed their interest in using iDiagnostics for the rapid detection of HIV and other infectious diseases.

There are hundreds of other exciting applications that will be completely new for the healthcare area. In our laboratory in North Carolina we are also working on longevity tests. These studies promise rapid progress in lengthening the average life span, and preventing metabolic disbalances that result in premature aging. Personalized precision medicine of the future, clinical and pre-clinical tests of new drugs, disease risks assessment, food and water safety, detection of allergens, and environmental and agricultural applications will benefit tremendously from iDiagnostics.


iDiagnostics - the Handheld Future of Medicine

accurate, rapid, personalized, yet affordable molecular diagnostics for home use

Donate to iDiagnostics project

Literature Cited


1. Makary MA, Daniel M,  “Medical error - the third leading cause of death in the US.” BMJ 2016; 353: i2139.


2. Leape LL, Lawthers AG, Brennan TA, Johnson WG. “Preventing medical injury.” Qual Rev Bull 1993;19:144-9.


3. Sotos JG, “Biotechnology and the lifetime of technical civilizations.” Cornell University Library, 2017 arXiv.org :1709.01149v1 [physics.pop-ph].


4. PCAST Letter to the US 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.


5. 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.


6. Arlett JL, Myers EB, Roukes ML, Comparative advantages of mechanical biosensors. Nat Nanotechnol. 2011 Apr;6(4):203-15.


7.  Asanov A, Zepeda A, Vaca L. A platform for combined DNA and protein microarrays based on total internal reflection fluorescence. Sensors (Basel). 2012;12(2):1800-15.


8. Asanov A, Zepeda A, Vaca L. A novel form of Total Internal Reflection Fluorescence Microscopy (LG-TIRFM) reveals different and independent lipid raft domains in living cells. Biochim Biophys Acta. 2010 Feb;1801(2):147-55.

The Ultimate Opportunity to Give Back to Society

We believe that donating to the iDiagnostics project represents the ultimate opportunity for members of The Giving Pledge and similarly positioned individuals to give back to society. The significance of this project for the survival and well-being of mankind is difficult to overestimate. As mentioned above, the iDiagnostics project will minimize the risks of pathogenic catastrophe and deadly medical errors, and will improve many areas of healthcare, by aiding everything from the elucidation of the mechanisms of diseases to early diagnosis and disease prevention.  

In spite of the gigantic commercial potential, this project does not pursue a commercial goal.  We believe that the potential social impact, rather than for-profit intentions, should be the main driving force of the iDiagnostics project. This project will break the ground for new type of moral technology, which is much needed in the area of healthcare and biological safety. Private donations and the non-profit status of the iDiagnostics project will create affordable access to this life-saving technology for every family on the globe.

It appears that the involvement of a venture capital firm or other traditional commercial routes would result in the emergence of one more expensive diagnostic technology, which is counterintuitive to our goal that is to make iDiagnostics affordable to everyone. Therefore, we address our quest for funding to members of The Giving Pledge and similarly positioned individuals. We believe that this project represents a truly unique and sensible opportunity to efficiently give back to society. Your support through donations, sponsorships, and/or grants will help to protect humanity, which today remains so fragile under the weight of many perils [1-4]. Thank you so much for your support! :-)

Technology: How Does iDiagnostics Work?                               Patent pending

Molecular markers are signatures of diseases. They appear in bodily fluids several months before a cancer tumor develops, and at least several weeks before a heart attack strikes, giving us enough time to prevent the disease. iDiagnostics is a patent pending technology, which is capable of detecting multiple molecular markers in a droplet of saliva, urine, sweat, blood, or other bodily fluid. It is designed to be minimally invasive and maximally precise.  Since many important biomarkers are not stable and do not endure shipping and certain sample preparation procedures, as mentioned above, it is important to perform the measurements shortly after taking the sample.  

Fig. 1 shows a photo and the schematics of iDiagnostics. The detection of biomarkers occurs in the middle of the cartridge, where an array of fluorescent bioassays is printed at the surface of the TIRF slide. If a specific biomarker is present in the sample, it binds to a specific spot in the microarray, and the event of binding results in the increase of fluorescence intensity of this specific spot, which is recorded by the cellphone. The cradle and cartridge integrate optics, microfluidics, electronics, and nanoengineered bioassays into one handheld device, which implements TIRF microarray technology. Fig. 2 shows that the excitation light enters the slide at its end, is reflected from the top and the bottom of the slide, and excites fluorescence of multiple bioassay spots that are arrayed at the bottom of the slide, where the bodily fluid contacts the array. Because TIRF implements a surface-selective technique, which probes only a sub-micron layer of the fluid,  bioassays that are immobilized at the surface are excited and fluoresce, while molecules and other particles in the bulk of solution are not excited, and respectively, do not fluoresce. This provides exceptional sensitivity and allows for the testing of complex biological fluids, such as whole blood, with no or minimal sample preparation, and therefore drastically reduces the turn-around time between the moments of  "sample-in" and  "result-out."

Classical TIRF microarrays operate with small, sub-monolayer amounts of antibodies and DNA probes immobilized on the surface; the fluorescence signal is small, and a low light photodetector (e.g. EMCCD camera) is necessary. In iDiagnostics the signal of TIRF arrays is enhanced by 3D encapsulation, which captures the excitation light and becomes an integral part of the lightguide. 3D encapsulation allows for the usage of larger amounts of antibodies per unit area of bioassay spot.  The signal from such arrays is a thousand-fold greater than that in classical arrays. The CCD cameras of cellphones are sensitive enough to detect the signal. In summary, iDiagnostics appears to be the ideal platform for interfacing antibody-based bioassays for detecting proteins and metabolites, and molecular beacon assays for measuring nucleic acids [7, 8].


Fig. 3. Molecular beacon assay for detection of DNA/RNA and immunoassay for detection of protein markers.

For the detection of DNA and RNA markers, iDiagnostics uses bioassays, termed molecular beacons. The principle of their operation is shown in left panel of Fig. 3. In the absence of target DNA or RNA, the fluorescence of a molecular beacon is quenched. Upon binding to target DNA or RNA the molecular beacon opens and its fluorescence is dequenched. Irrelevant, non-target DNA or RNA do not open the molecular beacon; its fluorescence remains quenched.

For the detection of protein and metabolite markers, iDiagnostics employs immunoassays based on antibodies, as shown in right panel of Fig. 3. Capture antibody, which is immobilized at the surface, selectively binds protein or metabolite molecular marker. The binding of the detection antibody labeled by a fluorescent tag, results in increase of fluorescence.  For more information about the principles of 3D-enhanced TIRF microarrays contact us by email: info@tirf-labs.com.


Dr. Luis Vaca

Dr. Alexander Asanov

 uTIRF biodetection station

iDiagnostics with cartridges

iDiagnostics2018.mp4

VIDEO

VIDEO

Open Innovation Business Model

The scale of this project is very large; it is impossible for a single firm to address the numerous challenges. We envision collective global effort of scientists, engineers, businessmen, and administrators in the framework of open innovation business model. By the beginning of 2018, six research groups worldwide have already joined the iDiagnostics project. Several other groups have expressed their interest in joining. We would like to invite more research groups to join this global effort, and are planning to intensively advertise our efforts and provide comprehensive support to our collaborators.  

This project will be using the Open Innovation Business Model, which stimulates the exchange of Intellectual Property (IP) between collaborators. TIRF Labs will supply unique hardware, software, cartridge blanks, development tools, reagent kits, methods and protocols to our collaborators to help interface their existing bioassays with the iDiagnostics platform and develop new assays. TIRF Labs will be delighted to license the IP of our collaborators and will offer them the opportunity to license our IP (in certain instances free of charge) to develop precise, rapid, and still affordable devices for molecular diagnosis and prognosis.

  Biodetection Station uTIRF. The feedback that we have received from our first collaborators has inspired us to develop a versatile instrument, uTIRF Biodetection Station, which is designed for different tasks  at the development stage from biomarker discovery to clinical testing. There are dozens of other applications related to molecular diagnostics, biomarker discovery, elucidating the mechanisms of disease, routine clinical analyses, and even the measurement of chemical analytes, where the uTIRF Biodetection Station can be used for as well. uTIRF is sensitive down to single molecules and is easy to use for numerous lifescience applications.

The project will be performed in two phases. In Phase 1, TIRF Labs will supply the uTIRF Biodetection Station and iDiagnostics Application Development Kit (ADK) to other research groups that are working in the area of molecular diagnostics. The ADK and uTIRF will facilitate the initial stages of the diagnostic cycle, i.e. creating panels of biomarkers, assay development and validation, and clinical testing. In Phase 2, which will start in 18-24 months after the beginning of Phase 1, we will start manufacturing iDiagnostics devices and begin supplying them to all interested parties, including the general public. Applications for the iDiagnostics platform include the diagnosis and prognosis of cancer, heart diseases, infectious diseases, longevity studies, food and water safety, military, forensic, environmental, and agricultural applications, as well as disease prevention actions and counter-measures against bioterrorism and naturally occurring diseases. For more information contact us by email: info@tirf-labs.com.

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 [5], 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.  

Fig. 5: Printing iDiagnostics microarrays and using uTIRF biodetection station for real-time microarray data acquisition and analysis.

Biographical Sketch. Dr. Alexander Asanov

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