How iDiagnostics technology can help to nice intentions of Google to improve the health care?
How iDiagnostics technology can help to nice intentions of Google to improve the health care?

iDiagnostics -  Turn your cellphone into an accurate and rapid, yet inexpensive molecular diagnostic device for home use

health project by TIRF Labs, Inc., Cary, North Carolina, USA,
Dr. Alexander Asanov and Dr. Luis Vaca

Video iDiagnostics Intro: http://youtu.be/GaXTjAyCLSE

 

Summary


TIRF Labs introduces cell phone based molecular diagnostics for home use. We know that early diagnosing saves lives, don't we? However, we are reluctant to submit ourselves for examination because it is costly and uncomfortable. Wouldn’t it be wonderful if you could turn your smartphone into a hospital laboratory and perform accurate diagnosing in the comfort of your home? Think of how that could help in monitoring the health of your family, as well as assisting frontier doctors in preventing the spread of Ebola and other infectious diseases. This technology has, in fact, been developed, and is named iDiagnostics.

Medicine today is extremely imprecise and depersonalized. It treats us assuming that we all are the same. However, every one of us is truly unique. We respond differently to everything, including prescription drugs. In the USA we pay $350 billion a year on prescription drugs, but one third of them do not work, often producing toxic side effects. In the research community, it is well understood that medicine should be personalized. In other words, it should be tailored to peculiar features of the molecular machinery of our bodies. iDiagnostics is a tool which will permit medicine to become personalized and accurate, as it should be. Today, in many instances, diseases are diagnosed too late, making it difficult to reverse or prevent the threat. Technologies that allow to precisely diagnose diseases have been developed and are available in centralized clinical laboratories. However, until now using them has been too costly, often uncomfortable, and involved visiting doctors. iDiagnostics will change the situation and allow you to perform precision diagnoses in the comfort of your home. You will know the results in a matter of several minutes, and your doctor will be able to adjust the treatment remotely, without you visiting his office.

 

What You Will Receive?

This project will result in two main products:

(i) iDiagnostics and test cartridges, shown in Figure 1, and

 


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

(ii) Application Development Kit (ADK) shown in Figure 2.

 


Figure 2. iDiagnostics Application Development Kit (ADK). For more information please visit www.i-diagnostics.net.

(i) iDiagnostics and disposable cartridges, shown in Figure 1, are designed for home use by everyone. They also can be used by medical doctors, first responders, clinical researchers, and other specialists. We anticipate that by October 2015 several tests, including food safety, allergens in food, prostate and breast cancer, will be approved by regulating agencies and available to our backers. Our adopter-pledgers will receive an iDiagnostics cradle with several cartridges from the list of approved tests. Major models of Android, Windows, and iPhone will be supported; please specify your model at the moment of pledging. Our adopter-pledgers will also receive several free cartridges that our collaborators and we will develop during the next two years. Each of our pledgers will have the opportunity to become a member of the home diagnostics community, which will help to develop new tests and make existing tests more accurate.

(ii) ADK (Application Development Kit), shown in Figure 2, is intended for researchers who are interested in interfacing their existing tests and developing new applications for iDiagnostics. Our pledgers who support ADK products will receive ADK at special Indiegogo price and also will have 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, we will be delighted to assist you in allocating a bright student and an exciting goal.

 What Will You Change?

Your support of the iDiagnostics project will change how medicine works. With iDiagnostics, you and your doctor will precisely know what is going on in your body, how your condition develops in time, and how your body responds to therapy or changes in your lifestyle. Today, there are three problems in diagnosis: (i) under-diagnosing - due to poor sensitivity of traditional tests, in which 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 (3) no-diagnosis - due to high cost and discomfort many of us prefer to avoid diagnosis. Being a sensitive, accurate, and inexpensive 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 fight these diseases.

Accurate and rapid diagnosis is essential for absolutely all healthcare actions. Detection of diseases, fighting cancer, heart and neurological diseases, prevention of epidemics, 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 on 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 yourownership of information about your health. You will own the data and decide whether to email them to your doctor or save on 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.


Idea of Cell Phone Based Diagnostics


Our cellphones are powerful computers equipped with super cameras. The idea behind iDiagnostics is to use them with a handheld cradle, which implements a super sensitive 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 the 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 fluid. 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 several minutes, will provide recommendations on what to do.


How Does iDiagnostics Work?


iDiagnostics is a technology which detects multiple molecular markers in a droplet of saliva, urine, sweat, blood, stool, or other bodily fluid. It is designed to be minimally invasive and maximally precise. Molecular markers are signatures 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 threat. iDiagnostics employs super sensitive technology, termed silk-enhanced TIRF microarray, 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 negligibly small rate of errors. TIRF microarrays are capable of detecting markers of three major classes: proteins, nucleic acids, and metabolites. 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.

Figure 3. Photo and schematics of iDiagnostics.

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.

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

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; 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.

 


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


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 on the right panel of Figure 5. For more information about the principles of silk-enhanced and classical TIRF microarrays please visit www.i-diagnostics.net and www.tirf-labs.com


iDiagnostics Technical Specifications

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. TIRF is an exceptionally sensitive technology capable of detecting biological particles down to single molecules. In iDiagnostics, TIRF allows for 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 protein, 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.

Figure 6. Downsizing TIRF microarray biosensors.

In 2013, as mentioned above, 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.


iDiagnostics Applications


Applications for iDiagnostics include diagnosing and prognosing cancer, cardio-vascular diseases, Alzheimer's disease and other neurological disorders, influenza, Ebola 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 the iDiagnostics platform and to develop new tests. To facilitate these efforts, we will supply the iDiagnostics Application Development Kit (ADK) shown in Figure 2. An ADK contains all necessary components for the development of diagnostics applications, including hardware, software, development tools, cartridge blanks, reagents, experimental protocols, and description of methods necessary for development.

In our laboratory in North Carolina we are finishing the development of 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 iDiagnostics tests for cardio-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 the longevity tests. These studies are promising rapid progress in the increasing of longevity and preventing metabolic disbalances that result in premature aging.

Personalized medicine, 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 from iDiagnostics.

How iDiagnostics Compares with Alternative Technologies?
We have carefully examined the multitude of alternative methods and found that iDiagnostics is a superior technology for home use diagnostics. To the best of our knowledge, iDiagnostics is the only technology which is accurate and rapid, yet can be downsized to an inexpensive handheld device. The projected cost of iDiagnostics is $400, and disposable cartridges are anticipated to cost $1-3. We are not aware of other technologies that could be as sensitive, accurate, rapid, and yet be as affordable as iDiagnostics.
After 9-11 followed by the anthrax letter attacks, 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 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 (www.cbrnhorizonscan.com), which ranked our classical TIRF array biosensors among the 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 diagnosis of diseases, (iii) the capability to simultaneously detect three classes of markers: proteins, nucleic acids, and metabolites. To the best of our knowledge, iDiagnostics is the only technology which is capable of providing precision and rapid molecular diagnosis at affordable cost.


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, Alexander Asanov, believe that I am well-suited to lead the iDiagnostics project. This project logically builds upon my prior work. In 2004-2012, 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. 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 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. Although I still speak with an accent, 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.


Open Innovation Approach


In order to make accurate diagnostics available to everyone, we are using an open innovation approach, which involves collaborative efforts with other research groups. We have successfully collaborated with several groups worldwide and plan extended collaboration to better meet the 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 - research group of Dr. Vaca from UNAM. We plan to further extend this approach 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.

 

Why Crowdfunding?


Our goal is to make accurate diagnosing affordable for all. Rather than selling iDiagnostics to a big-name company, we are turning to you on Indiegogo for funding, so that we can guarantee affordable access to this life-saving technology for you and every family around the globe.

It appears that acquisition of iDiagnostics technology by a large firm would produce too 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 capital firms appears to be even less efficient than the possible acquisition of iDiagnostics by a large firm. Unfortunately, the rate of success for a typical venture 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.

Valley of Death - is the term that the business development community uses to designate the dramatic period of time that occurs between creating a prototype and manufacturing the product. Indeed, many nice technologies have paved the road of the Valley of Death, because they did not get funds to make the transition to manufacturing. Crowdfunding is a new mechanism, which is changing the game. On Indiegogo you, using your hard-earned dollar, are voting for an innovation, which you want to see in your hands. We believe that iDiagnostics is one such innovation. It will have enormous social impact, save millions of lives, and overall improve healthcare for everyone around the globe. We hope that you will join us. It will be more than just a new technology. There also will be a new community, which will work together to efficiently improve the quality of healthcare.


Budget and Timeline

 

 


Disclaimer


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

The field of life-sciences, in general, and the area of molecular biology, in particular, operate with powerful technologies that are improving the quality of our lives. However, these powerful tools, if used improperly, can cause adverse effects. We believe that scientists should be responsible for the results of their studies. It is our company policy and the responsibility of our workers to foresee the 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 documentshttp://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm089543.htm

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

Design Considerations for Devices Intended for Home Usehttp://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM331681.pdf

Guidance for Molecular Diagnostic Instruments with Combined Diagnostic and Research Functionshttp://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. The research and development have worked, the prototyping and low-volume manufacturing has been done. Now, the risks are associated with the transition from prototyping and 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 backers with full satisfaction. Keeping our customers and backers updated about our progress and receiving feedback from them is our priority. If there are unexpected issues or delays, we will inform you promptly.

Other Ways You Can Help


If you can't contribute monetary, but feel that you wish to help to iDiagnostics,

Please spread the word about iDiagnostics out: tell your family and friends, use Twitter, Facebook, and other social networks. Prefundia has excellent sharing tools! Please use them!

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