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iDiagnostics - the cellphone 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

Cellphone Based Molecular iDiagnostics

by TIRF Labs

www.tirf-labs.com

Figure 1: iDiagnostics cradle with cell phone and cartridges for home use molecular diagnostic tests.

Turn your smartphone into an accurate, rapid,  yet inexpensive molecular diagnostic device for precision medicine

Pursuing the objective of distributing iDiagnostics development tools, we will keep in mind that the ultimate goal of decentralized precision diagnostics is to make it available and affordable for all. An early prototype of iDiagnostics and disposable cartridges is shown in Figure 1. It will be designed for home use by minimally trained individuals, similar to pregnancy test strip. However, iDiagnostics also can be used by medical doctors, first responders, clinical researchers, and other specialists. We anticipate that twelve months after we receive necessary funds, several 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.  

iDiagnostics6.mp4

What Will We Deliver?


Our goal is to make iDiagnostics available and affordable for every family on the globe. We believe that in several years, in the medicine cabinets of most families, there will be an iDiagnostics device, similar to that shown in Fig. 1, and a dozen of different cartridges dedicated to different diagnostic tasks, from food and water safety to predicting cardio-vascular problems; It will be affordable to every family on the globe. While this ambitious goal is several years away (Fig.1 shows its early prototype), during Phase 1 of the project we plan to make the iDiagnostics Application Development Kit  (ADK)  (Fig. 2) available to each member of biodetection community. It appears that the gigantic task of changing the paradigm to individualized precision medicine is too difficult for a single firm, even a big one. Therefore, we envision distribution of the iDiagnostics ADK among the biodetection/diagnostics community so that thousands of research groups worldwide will be equipped with advanced tools for the development of precision diagnostics tests.

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Dr. Alexander Asanov

Dr. Luis Vaca

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 iDiagnostics Brochure

iDiagnostics ADK

TIRF Labs has developed and prototyped a cellphone based diagnostic device - iDiagnostics™, which uses enhanced TIRF microarray technology. TIRF stands for Total Internal Reflection  Fluorescence  - the core technology of TIRF Labs. Classical TIRF is sensitive down to a single molecule, is rapid, selective, and can be highly multiplexed - detecting thousands of bioanalytes simultaneously. The iDiagnostics biosensor is small and inexpensive, yet accurate and rapid tool with analytical power similar to that of large and expensive clinical laboratories. iDiagnostics can be used for personal diagnostics, early detection of cancer, food safety applications, measuring individualized response to therapies and diets, and for the use in field environment, where electrical outlets and running water are not available. Additionally, the high accuracy, reliability, and extraordinary analytical power pave the road for many applications of iDiagnostics platform in laboratories.


iDiagnostics consists of a cradle and a disposable cartridge.  iDiagnostics uses a smartphone to acquire and analyze the real-time response of the TIRF microarray.  iDiagnostics features novel types of microarrays - TIRF microarrays that simultaneously, in real-time detect proteins, nucleic acids, and metabolite biomarkers of different diseases.  iDiagnostics requires no or minimal sample preparation and is capable of detecting either a single or up to several thousands of molecular markers in a droplet of blood or any other biological fluid.


iDiagnostics employs a novel patent-pending sensor technology, which is based on total internal reflection fluorescence (TIRF).  iDiagnostics uses the unique property of a natural material, silk fibroin, a protein created by spiders, the larvae of Bombyx mori, and other insects. Silk fibroin captures the excitation light and serves as an extension and integral part of the TIRF lightguide, thus increasing the surface area of TIRF lightguide, where antibodies and probe DNA molecules can be immobilized. Silk fibroin increases the amount of immobilized bioassay molecules by a thousand-fold. The silk fibroin scaffolding also provides a biologically friendly environment to bioassays increasing their sensitivity and selectivity. Finally, silk fibroin stabilizes antibodies and prolongs their shelf life to several months without degradation of their avidity.


Micro-RNA circulating in blood can be detected with a Limit of Detection (LOD) in the range of 10-18 M. For other assays that measure protein and metabolite concentrations, the LOD depends on the assay. For certain antibody-based assays it is at the level of ~10-15M. The broad dynamic range of iDiagnostics sensor covers the entire spectrum of clinically significant concentrations of bioanalytes. Unlike classical TIRF microarray technology that generates a weak signal due to small, sub-monolayer amounts of antibodies and probe DNA immobilized on the plain surface, and hence, requires an expensive low light photodetector, e.g. EMCCD camera, iDiagnostics, due to its unique features, uses larger amounts of antibodies per unit area of bioassay spots and generates a signal a thousand-fold greater than that in classical TIRF. With the iDiagnostics sensors, CCD cameras of cell phones are sensitive enough to detect the signal. Current models of iDiagnostics sensors have been designed to work with iPhone, HTC One, and Windows smart phones.


Because of enhanced sensitivity and improved selectivity, accuracy, miniaturization, and other advantages, the iDiagnostics biosensor will become a popular device for hundreds of applications, including molecular diagnostics of cancer and other diseases, personalized medicine, sport medicine, and food safety. In our own laboratory we are currently developing assays, which would enable one to perform early diagnosis and accurate prognosis of the prostate and breast cancers.


We pursue the business model of open innovation for collaborative development of molecular diagnostics applications for iDiagnostics platform. If you are developing a molecular diagnostics (MDx) system based on luminescent assays, including ECL, we invite you to collaborate with us to make your and our developments available for millions of future user of iDiagnostics sensors. TIRF Labs will be delighted to license your Intellectual Property (IP) and offer you the opportunity to license our IP to develop accurate and rapid, yet affordable devices for molecular diagnosis and prognosis. We are also looking for enthusiastic people from scientific, clinical, and general population communities, who would be interested in accelerating of the progress of this technology either as researchers and clinicians in their respective professional niches, or private citizens by making financial contributions for the advancing of new technology to the stage, where it becomes an indispensable tool for molecular diagnostics.  


Our goal is to make accurate and rapid molecular diagnostics devices available to the general public. This goal involves numerous challenges and requires efforts of enthusiastic multidisciplinary team. If you are interested to become a part of this team, please send us an email to <info@tirf-labs.com>.


  TIRF Principles. Briefly, TIRF employs the phenomena of total internal refection and evanescent wave to selectively excite fluorophores located at the surface and in close proximity (100-200 nm) to the surface of a glass or plastic slide. Fluorophores that are in the bulk of solution are not excited and do not fluoresce. Such exceptional spatial selectivity enables TIRF with numerous advantages, including the ultimate limit of detection - single molecule. TIRF minimizes the background and allows for monitoring in real time the molecular dynamics at the level of single molecules.  TIRF allows for minimizing of sample preparation; it can analyze whole blood or other complex biological fluids.  More »

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TIRF - Total Internal Reflection Fluorescence also known as evanescent wave fluorescence


Accurate and Affordable Diagnostics is on its Way to Your Home


There is a gigantic gap between current knowledge of how molecular machinery of our bodies works, and how modern medicine is treating us. Today, we better understand  the complex nature of cancer, Alzheimer’s, and other diseases. We have realized that each of us is truly unique, in every way, including our risks for the diseases and our responses to therapies and diets. However, the medicine is currently treating us as if we all are the same. This situation should and will change. Medicine should become precise, personalized, and affordable.

Everything in medicine starts from the diagnosis. Currently, diagnosing is set up to be maximally imprecise and expensive. We need to change that. We need an accurate and inexpensive diagnostic technology. TIRF Labs has developed such a technology, and we have named the technology iDiagnostics.  IDiagnostics will rectify the situation and make modern medicine more precise and less expensive. iDiagnostics uses the photocamera and the computer of your cellphone to measure the response of an array of fluorescence assays printed on a disposable cartridge. You insert the respective cartridge into the cradle, apply a droplet of blood, saliva, sweat, or urine, and in a matter of minutes the smartphone will detect up to a hundred of molecular markers that identify a disease or its absence. Moreover, molecular markers will determine your risks and predict how your condition will tend to develop with time. You can send the data to your doctor or to your computer to store them for future use.

To accelerate the transfer of iDiagnostics to the market, we are offering the iDiagnostics Application Development Kit (ADK), which consists of the turnkey uTIRF Cube system, a smartphone, iDiagnostics cradle, cartridge blanks, software, hardware, development tools, reagent kits, and protocols - everything what is needed for expedited development of diagnostic tests.

Currently, there are enormous losses caused by the imprecise diagnosing, including premature deaths due to late diagnosis. In many instances, there is no diagnosis at all, because of the high cost or too much invasiveness. Today diagnoses involve visits to medical offices and labs that are not cheap and often too invasive. Most of us tend to procrastinate the diagnosing until it is too late. iDiagnostics is a small but powerful device, which will be a big game-changer – it will bring the diagnosis to your home, make it accurate, predictive, minimally invasive, yet inexpensive.

iDiagnostics technology is the result of 9 year-effort of TIRF Labs’ team of scientists and engineers. We received over $4M from the U.S. government in research grants and developed the advanced diagnostic technology, called the TIRF microarray. TIRF uses fluorescence and stands for Total Internal Reflection Fluorescence. We developed a benchtop analytical grade instrument based on TIRF microarray technology. It is sensitive down to a single molecule and capable of detecting thousands of molecular markers from a small 0.1-mL sample of biofluids, including blood. We also developed a portable version of TIRF microarray device, which runs on batteries, has a computer on the board, illuminator, and everything else. We also developed and commercialized several TIRF accessories for microscopy and spectroscopy. Over one hundred research groups worldwide bought our TIRF products and generated unique data for several areas of life sciences. Our turnkey TIRF instruments are equipped with low light scientific grade CCD cameras that, unfortunately, are expensive.

What Will You Change?


Your support of the iDiagnostics project will change the way how medicine works. Currently, medicine assumes that we all are the same, while everyone of us is indeed unique. We respond differently to everything, including therapies. Blood transfusion is a rear exception in modern medicine, where patients are divided into several groups in accordance with their individual differences. In the future, the personalized approach based on precision diagnosing and individually tuned treatment will become common.  Affordable accurate diagnosing is an essential part of this future. With iDiagnostics, you and your doctor will know precisely what is going on in your body, how your condition develops with time, and how your body responds to therapy or changes in your lifestyle. Today, there are three problems in diagnostics: (i) under-diagnosis - due to poor sensitivity of traditional tests diseases often remain undetected; (ii) over-diagnosis - due to the high rate of false positive responses the presence of a disease is erroneously reported, while, in fact, there is no threat; and (iii) no diagnosis - due to high cost and discomfort many of us prefer to avoid diagnosis. Being a sensitive, accurate, inexpensive, non-invasive or minimally invasive technology, iDiagnostics will solve all three problems. Early detection of cancer, Alzheimer's, cardio-vascular and infectious diseases, food safety, and other areas will benefit tremendously from the use of iDiagnostics. Your support will help to rectify the problem of imprecise or no-diagnosing, and thus will facilitate to fight numerous diseases efficiently .


Accurate and rapid diagnosis is essential for absolutely all healthcare actions. Detection of diseases, fighting cancer, heart and neurological diseases, prevention of epidemics, including Ebola, Zika, HIV/AIDS, avian flu, and SARS, testing new drugs, and many other areas critically depend on accurate and rapid diagnosis. Your support will significantly accelerate progress in these areas.


Today, our doctors and insurance companies possess information about our health. We seldom keep the results of laboratory tests in our files, despite their importance to us in being better diagnosed in the future. For our children, who carry similar genes, the results of our diagnoses have valuable information for their health. iDiagnostics will seamlessly enable your ownership of information about your health. You will own the data and decide whether to send them to your doctor or save them in your files. The technological opportunities for these changes have been embedded into iDiagnostics devices. Your support will help you to become the owner of information about your health.

The iDiagnostics ADK, shown in Figure 2, is intended for researchers who are interested in interfacing their existing tests and developing new applications for iDiagnostics. Several research groups worldwide have requested the iDiagnostics ADK. Several our collaborators from the academic sector and industrial groups will receive an ADK set at a special promotional price. We offer the opportunity to sponsor a university student project, which will use the ADK for the development of molecular diagnostics tests. If you do not have a student in mind, but are willing to sponsor one for diagnosing a specific disease, we will be delighted to assist you in allocating a bright student and a valuable goal.

Figure 2: iDiagnostics Application Development Kit (ADK). For more information see iDiagnostics webpage.

Idea of Cellphone Based Diagnostics


Our cellphones are powerful computers equipped with low light super cameras. The idea behind iDiagnostics is to use them with a handheld cradle, which implements a supersensitive bio-detection fluorescence technology, called TIRF microarrays. The use of iDiagnostics is as simple as blood glucose tests available today for diabetic patients. You start the iDiagnostics app on your phone and follow  simple instructions. The app will instruct you to put your cellphone into the cradle, insert a cartridge, and apply a droplet of saliva, urine, sweat, blood, or other bodily fluids. The fluid will flow inside the cartridge over the TIRF microarray; which will detect the presence or absence of numerous molecular markers. Massive amounts of information will be obtained by taking pictures of the response of the TIRF microarray. The iDiagnostics app will analyze the images, and, in a matter of a few minutes, will provide recommendations on what to do.

How Does iDiagnostics Work?


iDiagnostics is a technology which detects multiple molecular markers of different classes in a droplet of saliva, urine, sweat, blood,  or other bodily fluid. It is designed to be minimally invasive and maximally precise. Molecular markers are precise signatures or “fingerprints” of diseases. They appear in biological 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 employs a super sensitive technology, called silk-enhanced TIRF microarrays, to detect molecular markers. Theoretically, thousands of bioassays can be included into a TIRF microarray. However, in most practical cases we do not need more than 20 markers to perform a test with a negligibly small rate of errors. TIRF microarrays are capable of detecting markers of four major classes: proteins, metabolites, DNA and RNA.  Traditional tests are based on a single class of markers and are often too imprecise.


Figure 3 shows a photo and the schematics of iDiagnostics. The cradle and cartridge integrate optics, microfluidics, an electrochemical system, electronics, and nanoengineered bioassays into one handheld device, which implements TIRF microarray technology.

iDiagnostics is based on the phenomenon of Total Internal Reflection Fluorescence (TIRF) (Figure 4), which occurs at the interface between a plastic or glass slide and biological fluid. If the fluorescence excitation light enters the slide at angles of 63 degrees or larger, the light will bounce from the top and the bottom of the slide and excite fluorescence of multiple bioassay spots that are arrayed at the bottom surface of the slide, where the bodily fluid contacts the array.


Because TIRF is 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 allows for the testing of complex biological fluids, such as whole blood, with no or minimal sample preparation, which drastically reduces the turn-around time between the moments "sample-in" and  "result-out."

A classical TIRF array, which is shown at the bottom of Figure 4, can use only a sub-micron layer of bioassays. Therefore, the fluorescence signal of classical arrays is low; expensive scientific-grade cameras are necessary to image them. In 2013, after experimenting with a multitude of materials, we  discovered that silk fibroin, the same natural protein that spiders use for their webs, tremendously enhances the signal of TIRF arrays. Silk fibroin is one of the few natural proteins whose refractive index is close to that of glass. This property is responsible for the beautiful shimmering of silk fibers in clothing. If deposited onto a glass or plastic slide, silk fibroin captures the excitation light, becomes an integral part of TIRF lightguide, and allows for an increase in the amount of immobilized bioassay molecules by a thousand-fold. Silk-enhanced TIRF arrays fluoresce brightly; and cell phone cameras are sensitive enough to detect their response. Additionally, silk is a remarkably stable protein. Its shelf life extends to several months and even years. Silk also stabilizes other biological molecules that otherwise would require refrigeration, a quality very desirable for applications in low resource settings.


For the detection of DNA and RNA markers, iDiagnostics uses bioassays, termed molecular beacons. In the absence of target DNA or RNA, the fluorescence of a molecular beacon is quenched. The left panel of Figure 5 illustrates that 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 Figure 5. For more information about the principles of silk-enhanced and classical TIRF microarrays please visit www.tirf-labs.com

Figure 4. Silk-enhanced TIRF microarray in comparison with classical TIRF microarray.

Figure 3. Photo and schematics of iDiagnostics.

Figure 5. Molecular beacon assay for detection of DNA and RNA markers and immunoassay for detection of protein markers.

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 the iDiagnostics project. This project logically builds upon my prior work. In 1999-2012, I served as Principal Investigator on several BAA and SBIR grants, awarded by NIH and HSARPA. I assembled and led a team of 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 TIRF technology 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  23rd 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 the society and believe that the development of iDiagnostics is the way, in which I can demonstrate my gratitude to America and the world.

Disclaimer


Neither human subjects nor laboratory animals are involved in this project. Genetically modified organisms and biologically hazardous materials are not involved either. 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, operate with powerful technologies that are 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 ten 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 group of transition-to-the-market risks, we are offering to the biodetection community iDiagnostics Application Development Kit (ADK). ADK will involve a number of diagnostics research groups with their own networks, which will facilitate entering of iDiagnostics into competitive biodetection market. The research and development for iDiagnostics have worked, the prototyping and low-volume manufacturing has been done. Now, a group of risks will be associated with the transition from low-volume manufacturing to mass 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 iDiagnostics to our customers with full satisfaction. Keeping our existing and prospective customers updated about our progress and receiving feedback from them is our priority. If there are unexpected issues or delays, we will inform our customers and supporters promptly.

How iDiagnostics Was Born


iDiagnostics is the result of a 9-year effort by our 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 - TIRF microarrays. As mentioned above, TIRF is an exceptionally sensitive method capable of detecting biological particles down to single molecules. In iDiagnostics, TIRF allows for the super-sensitive detection of proteins, DNA, RNA, metabolites, and selected chemical agents. The sensitivity and dynamic range of iDiagnostics is sufficient for detecting virtually all clinically significant proteins, RNA, DNA, and metabolite markers. Figure 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.

Figure 6. Downsizing TIRF microarray biosensors.

iDiagnostics Applications


Future applications for iDiagnostics will include diagnosis and prognosis of cancer, cardio-vascular diseases, Alzheimer's disease and other neurological disorders, influenza, Ebola, HIV/AIDS, Zika and other infectious diseases, food safety, biodefense, forensic, environmental, and agricultural analyses. 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 tests that can be developed for the iDiagnostics platform. For a single company it is too difficult, if not impossible, to develop all these numerous applications. Therefore, we invite other research groups worldwide to join our virtual team to interface their existing tests with iDiagnostics platform and develop new tests. To facilitate these efforts, we are offering the iDiagnostics Application Development Kit (ADK) shown in Figure 2. ADK contains all necessary components for the development of diagnostics applications, including hardware, software, development tools, cartridge blanks, reagents, experimental protocols, and the description of methods necessary for development. We envision that the ADK will be our main product at the initial stages, before the first iDiagnostics tests are approved by FDA. We envision that there will be large market for ADK, because there are thousands of research groups worldwide that develop diagnostic panels, discover and validate molecular markers and investigate molecular mechanisms of cell signaling. These research applications do not need FDA approvals, but they will pave the road to medical use of iDiagnostics.

In our laboratory in North Carolina we are developing diagnostic and prognostic tests for breast and 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 tests for early diagnosing of 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 heart diseases. The Laboratory of Molecular Virology at the Food and Drug Administration expressed their interest in using iDiagnostics for rapid detection of HIV and other infectious diseases.

There are hundreds of other exciting applications that will be totally new for the healthcare area. In our laboratory in North Carolina we are working on longevity tests. These studies are promising rapid progress in the increase of length of life 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, environmental and agricultural applications will benefit tremendously with iDiagnostics.

iDiagnostics Technical Specifications

How iDiagnostics Compares with Alternative Technologies


We have carefully examined the multitude of alternative methods and found that iDiagnostics is a superior  technology for precision medicine, including home use diagnostics. To the best of our knowledge, iDiagnostics is the only technology which is accurate and rapid, multiplexed along four major classes of molecular markers, yet can be downsized to an inexpensive handheld device. The projected cost of iDiagnostics cradle is $200, and disposable cartridges are anticipated to cost $1-3. We are not aware about other technologies that could be as sensitive, accurate, rapid, detect all four major classes of markers, and yet be affordable. The closest competing technology appear to be biodetection based on electrochemiluminescence (ECL) assays. ECL assays, however, require labor intense sample preparation. Additionally, ECL detection requires both electrochemical and luminescence subsystems, which results in larger costs of the system.


After 9-11 followed by the anthrax letters attack, the U.S. government invested over $70 billion in bio-defense. There is no analytical technique that has not been tried for bio-detection. However, most of the techniques are too imprecise or too costly. The Department of Defense is carefully monitoring existing and emerging technologies that can be used for protection of the U.S. soldiers against biological warfare agents. In 2013 DOD issued a 663-page document [1], which ranked our classical TIRF array biosensors among most promising devices that are well-suited 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 sufficient for detection of virtually all clinically significant markers, (ii) the broad dynamic range, which covers the entire spectrum of bio-marker concentrations that are clinically significant for the diagnosing of diseases, (iii) the capability of simultaneously detecting three or more classes of biomarkers: proteins, nucleic acids, and metabolites. To the best of our knowledge, iDiagnostics is the only technology which is capable of providing such combination of advantages for precision and rapid molecular diagnosing, yet at an affordable cost.

Why We Are Asking for your Support


Our goal is to make accurate diagnosis affordable to every family on the globe. Rather than involving a venture capital or selling iDiagnostics to a big-name company, we are seeking government grants, sponsorships, and donations from individuals and organizations, so that we can guarantee affordable access to this life-saving technology - precision medicine for you and every family on the globe. We are not interested to create just one more expensive diagnostic technology for centralized laboratories.


It appears that the acquisition of the iDiagnostics technology by a large firm would produce one more costly diagnostic system, which the majority of population would not be able to afford. Indeed, the goal of large firms is to generate maximum income for their shareholders. It would be against their rules to sell iDiagnostics at a price that is significantly lower than the current market price for similar systems.


The involvement of venture or angel capital firms appears to be even less efficient than the possible acquisition of the iDiagnostics by a large firm. Unfortunately, the rate of success for typical venture/angel capital firm is less than 5%, meaning that just one company, which is successful, should cover losses incurred by 19 unsuccessful startups that did not make it to the market.


We believe that iDiagnostics project is an innovation, which will have enormous social impact, save millions of lives, and overall improve the healthcare for everyone on the globe. We hope that the US government, individual and institutional sponsors, and eventually the general public will support the iDiagnostics project. It will be more than just an exciting new technology. This project will also create a new community, which will work together to efficiently improve the quality of healthcare.

Open Innovation Approach


In order to make accurate diagnostics available to everyone, we are using the “open innovation” business model, which involves collaborative efforts with other research groups. We have successfully collaborated with several groups worldwide and plan extended collaboration to better meet a broad spectrum of needs of our customers. Several of our products, including iDiagnostics, have been inspired by our customers and collaborators. iDiagnostics has been developed in collaboration with one of our long-term partners - the research group of Dr. Vaca from UNAM. We plan to further extend the approach of “open innovation”, because we believe that knowledge in the field of life sciences is broadly distributed. Innovations and efficient transfer of them to the market place assumes close collaboration with external research groups. To stimulate the flow of innovations in and out of our company, we will offer to license the intellectual property of our collaborators and will offer them the opportunity to license our technologies.

About the iDiagnostics project


TIRF Labs introduces a supersensitive, accurate, rapid, yet affordable diagnostic technology, which we named “iDiagnostics.” It uses the photo camera and computing capabilities of a cellphone to measure and analyze the response of a microarray of bioassays printed on the surface of TIRF sensor chip. TIRF stands for Total Internal Reflection Fluorescence -  our core technology. TIRF is a uniquely advantageous method, sensitive down to a single molecule and capable of detecting multiple biomarkers - from a few to several hundreds - simultaneously. Panels of several biomarkers provide accurate “fingerprints” of diseases. iDiagnostics detects biomarkers of four different classes: proteins, metabolites, DNA, and RNA. The detection of different classes is necessary for accurate diagnosing.

iDiagnostics will become an indispensable tool for the precision medicine of the future. Despite its small sizes and low cost, iDiagnostics will be as accurate and precise as a large centralized clinical laboratory. We are closely familiar with competing analytical technologies applicable for molecular diagnostics. Partially, these technologies have been surveyed in the DOD review [1]. Our TIRF array technology and devices were ranked high in the survey [1]. From the standpoint of technical performance, the closest competitor of iDiagnostics is Electro-Chemi-Luminescence (ECL). However, for precision medicine of the future, for which the factors of low cost and decentralized home use are of paramount importance, ECL is far behind iDiagnostics.

This project seeks government grants, sponsorships from individuals and organizations, and donations from individuals and organizations. At the present time, we are reluctant to involve a venture capital or for-profit partnership with large firms. It appears that these routes would result in one more expensive diagnostic technology, while the precision medicine of the future requires it to be available to everyone. IDiagnostics will help to rectify one of the most fundamental problems of modern medicine - inaccurate diagnoses. According to recent study from Johns Hopkins University, medical errors are the third leading cause of death in the USA  [2. Makary M.A., Daniel M., BMJ 2016; 353: i2139]. Inaccurate diagnoses represent the forefront of medical errors. False positive, false negative diagnoses, and “no-diagnosis” due to discomfort of costly invasive procedures, account for the large number of medical errors. iDiagnostics will rectify the problem.

This project will make accurate, rapid, and minimally invasive diagnostics available to everyone. We envision two phases of the project. During Phase 1, TIRF Labs will distribute the iDiagnostics Application Development Kit (ADK) to the diagnostics community. The ADK will equip research groups with advanced tools that will facilitate the discovery of biomarkers and simplify the interfacing of respective existing bioassays with the iDiagnostics platform. We have already received numerous requests for the ADK from research groups worldwide. Collaborating with other groups, we will pursue the business model of  “open innovation,”  which assumes a two-way exchange of ideas and innovations between other research groups and TIRF Labs.  Phase 1 will create a broad base of groups that are practically using supersensitive, accurate, and rapid diagnostic technology in their labs and approved clinical studies. In Phase 2, TIRF Labs will perform the transition from prototypes to the large scale manufacturing of iDiagnostics devices. We also envision that routine blood and urine tests will be interfaced with the iDiagnostics platform, which will allow to transfer the entire spectrum of analyses from current laboratory-centered approach to person-centered diagnostics.  

The challenge of creating a revolutionary new, accurate, rapid, and personalized diagnostics can not be adequately addressed by a single firm. Therefore, we carefully plan to involve multiple research groups into this project, from the entire diagnostics community worldwide. Together, we will build the foundation for precision medicine.The unique set of iDiagnostics’ advantages, which is not found in competing technologies, provides the basis of our confidence that iDiagnostics is far ahead of the competition. We invite you to become a part of this exciting process of creating the precision medicine of the future. There is no alternative to iDiagnostics in decentralized, personalized precision medicine. Please consider donating or sponsoring the iDiagnostics project. iDiagnostics will allow you to perform precision diagnoses, predictive and preventive tests in the comfort of your home. >> More>>


iDiagnostics - the Cellphone Future of Precision Medicine

accurate, rapid, personalized, yet affordable molecular diagnostics

Detection technology

Real-time TIRF microarrays

Excitation light

Blue, green or red light, eye safe

Excitation mode

Total internal reflection

Range of fluorescence wavelengths

490 -1000 nm

Photodetector

Cellphone photocamera

iDiagnostics application software

iOS, Android, and Windows Phone

Supported Cellphones

iPhone, Android, and Windows main models

Connectivity

Bluetooth 4.0

Biofluid volume sample

0.1 ml - 0.3 ml

Classes of bioanalytes detected

Proteins, nucleic acids, metabolites, etc

Number of bioassays in microarray

1-6,000

DNA and RNA limit of detection

Attomolar - 10^-18 mol/liter

Protein limit of detection

Femtomolar - 10^-15 mol/liter

Metabolite limit of detection

Femtomolar - 10^-15 mol/liter

Measuring time

1-10 min

Battery

48 hours



Literature Cited

1. 2013 Global CBRN Detector Market Survey, Downloaded on May 1, 2015 from URL: www.cbrnlibrary.com

http://www.cbrnlibrary.com/documents/Global%20CBRN%20Detector%20Market%20Survey_web.pdf


2. Makary M.A., Daniel M.,  Medical error - the third leading cause of death in the US; BMJ 2016; 353: i2139.

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