Total Internal Reflection Fluorescence
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Single Molecule Detection, Super Resolution Microscopy, sm-FRET, Single Cell Analysis, Assay Development, Real-time Microarrays, Cell Membrane Studies,
TIRF microscopy, TIRF accessories for fluorometers, TIRF electrochemistry, TIRF dielectrophoresis, iDiagnostics - cellphone based TIRF, and more>>>
Open Innovation business model for the collaborative development of iDiagnostics (iTIRF microarray) molecular diagnostic products
Many years of research at TIRF Labs resulted in the development of the concept of the cellphone-based diagnostic device - iDiagnostics (iTIRF microarrays). TIRF stands for Total Internal Reflection Fluorescence - our core technology. TIRF is sensitive down to single molecules, rapid, selective, and can be highly multiplexed - it can detect thousands of bioanalytes simultaneously. The iDiagnostics (iTIRF) biosensor is a small, inexpensive, yet accurate and rapid tool with analytical power similar to that of large and expensive clinical laboratories. iDiagnostics (iTIRF) can be used for personal diagnostics, early detection of cancer, food safety applications, for measuring individualized responses to therapies, 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 the iDiagnostics (iTIRF) platform in laboratories.
iDiagnostics (iTIRF) consists of a cradle and a disposable cartridge. iDiagnostics uses an iPhone or other smartphone to acquire and analyze the response of real-time TIRF microarrays. iDiagnostics (iTIRF) features the novel type of Molecular Diagnostics (MDx) - TIRF microarrays that simultaneously, in real-time, detect protein, nucleic acid, 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 (iTIRF) employs a novel patent-pending sensor technology, which is based on total internal reflection fluorescence (TIRF). iDiagnostics (iTIRF) uses unique property of 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 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 the 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 the iTIRF 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 expensive low light photodetectors, e.g. EMCCD cameras, iTIRF, due to it’s 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 iTIRF sensors, the CCD cameras of cell phones are sensitive enough to detect the signal. Current models of iTIRF sensors have been designed to work with iPhones 4 and 5, HTC One, and some other smart phones.
Because of enhanced sensitivity and improved selectivity, accuracy, miniaturization, and other advantages, the iDiagnostics (iTIRF) biosensor will become a popular device for hundreds of applications, including molecular diagnostics of cancer and other diseases, personalized 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 the collaborative development of molecular diagnostics applications for iTIRF platform. If you are developing a molecular diagnostics (MDx) system based on luminescent assays, we invite you to collaborate with us to make your and our developments available to millions of future users of iDiagnostics (iTIRF) 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.
For financial contribution, please donate to our cancer MDx projects using the PayPal link. Your donation will enable faster progress in developing personalized iTIRF biosensors for diagnoses of prostate and breast cancer as well as different other diseases.
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 an enthusiastic multidisciplinary team. If you are interested in becoming a part of this team, please send us an email to <email@example.com>.
Business and Sponsorship Opportunities in the Area of Molecular Diagnostics
TIRF Labs is seeking private and institutional donations, U.S. government and international grants, as well as for-equity investments to develop cancer diagnosis and prognosis applications for the iDiagnostics (iTIRF) platform. If you are interested in accelerating the development of rapid, accurate, and affordable biosensors for the diagnosis and prognosis of prostate and breast cancer, as well as other types of cancer, please donate to TIRF Labs using the PayPal button.
We pursue the business model of Open Innovation for the collaborative development of molecular diagnostics applications for the iDiagnostics (iTIRF) platform. If you are developing a molecular diagnostics (MDx) system based on luminescent assays, we invite you to collaborate with us to make your and our developments available to millions of future users 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.
TIRF Labs will be pleased to collaborate with academic, industrial, and government research groups to develop MDx applications for iDiagnostics (iTIRF) platform. At the initial stage of iDiagnostics project, which will start in the third quarter of 2014, TIRF Labs will offer iDiagnostics Molecular Diagnostics Application Development Kit. We are currently accepting preliminary orders for the iDiagnostics (iTIRF) Application Development Kit. We anticipate that diagnostics community, including academic, industrial, and government research groups, will create superior clinical applications for accurate diagnosis and prognosis using the iDiagnostics (iTIRF) platform.
Competitive Advantages. iDiagnostics (iTIRF) has the potential to provide unprecedentedly accurate and rapid diagnosing due to its superior sensitivity, multiplicity, and rapid rate of response. One of the unique features of iDiagnostics (iTIRF) involves the parallel detection of multiple molecular markers of different classes, including protein, nucleic acid, and metabolite markers. There are no perfect single biomarkers of cancer and other diseases. Typically, single-marker assays exhibit large rate of false positive responses. However, the multiplexed detection of a panel of markers allows for the reduction of the probability of false positive responses to negligibly small levels, provided that the occurrence of the markers is not correlated.
iTIRF microarrays include internal positive and negative controls and luminescence standards for normalization and calibration, which provides high reliability and a broad dynamic range to analyses. iDiagnostics sensors also support other fluorescence and luminescence assays, including bio-luminescence, and Electro-Chemi-Luminescence (ECL).
Applications for the iDiagnostics (iTIRF) platform include the diagnosis and prognosis of cancer, heart diseases, STD's, influenza, other infection diseases, food safety, biodefense, forensic, military, environmental, and agricultural analyses.
iDiagnostics (iTIRF) integrates optics, microfluidics, electronics, electrochemical system, and nanoengineered bioassays into one handheld device. Analyses are performed in the format of real-time iTIRF microarrays that are capable of parallel detection up to thousands of analytes, including toxins and chemical agents. The iDiagnostics sensor detects unlabelled molecular markers using reagentless bioassays based on DNA molecular beacons and aptamer- or antibody-based beacons.
iDiagnostics (iTIRF) requires no or minimal sample preparation and is capable of analyzing complex biological fluids, including whole blood, saliva, and urine. In contrast to traditional microarrays that detect only end-point results, iTIRF monitors the entire course of association and dissociation kinetics. Typically, molecular markers are detected several seconds after the sample is applied.
Our goal is to make accurate and rapid MDx sensors available to the general public. This goal involves numerous challenges and requires efforts of enthusiastic multidisciplinary team. If you are interested in becoming a part of this team, please send us an email to <firstname.lastname@example.org>.
iDiagnostics sensors are well-suited for early detection and accurate prognosis of cancer. We are developing breast and prostate cancer detection applications in our own laboratory.
Market. The iDiagnostics sensor targets rapidly growing market. In 2006, the MDx market was $16B, in 2011 - $37B , and is anticipated to attain $92B by 2016.
Due to several unique advantages, there is a good chance that iDiagnostics biosensors will become a significant part of this large market. We envision a family of iDiagnostics cradles for popular cell phones: iPhone, HTC One, Nokia, Samsung, other smartphones, as well as photocameras. At the present time (January 2014), we are in position to offer iDiagnostics cradles for iPhone, HTC One, and similar cell phones. We also offer cartridge blanks and reagent kits to facilitate independent development of iDiagnostics (iTIRF) applications.
We anticipate a large response for iDiagnostics sensors. However, at the present time each unit of iTIRF cradles and cartridges is manufactured individually. We are looking for funds to arrange cost-efficient manufacturing using injection-molded parts and develop iDiagnostics applications for iOS, Android, and Windows Phone OS.
We envision rapid progress and plan to supply to our MDx customers iDiagnostics cradles, cartridge blanks, cartridge preparation protocols, reagent kits, all necessary hardware, software, and molecular-ware to facilitate interfacing of bioassays, sample preparation, and data analysis for MDx applications, including the diagnosis and prognosis of cancer, heart diseases, infection diseases, food safety, environmental, and agricultural applications. At the same time, we will be developing several MDx applications in our own laboratory. If you are interested in learning about our progress, please send us an email to <email@example.com>.
TIRF Labs introduced iDiagnostics technology at the following events:
iDiagnostics Cradles with iPhones
and Sensor Cartridges
To collaborate, to partner, or to invest please send us an email to <firstname.lastname@example.org>
Literature (Selected publications of our customers and our own data generated by TIRF Lab’s products)
1. Asanov A. “TIRF-EC Biosensors Massively parallel DNA and Protein Microarrays for Accurate and Rapid Detection of Pathogens.” Biodetection Technologies 2007. Knowledge Press, Brookline, MA. 4th Edition, 2007, Chapter 17, p. 373-396, isbn # 1-59430-126-3.
2. Asanov A. “TIRF-EC Biosensors with Reagentless Bioassays for Rapid and Accurate Detection of Pathogens.” Biodetection Technologies 2008. Knowledge Press, Brookline, MA. 5th Edition, 2008, Chapter 8, p. 155-190, isbn # 1-59430-137-9.
3. Asanov A., Wilson W., and Oldham P. “Regenerable biosensor using total internal reflection fluorescence with electrochemical control”. US Patent 6,511,854. Publication Date: 2003-01-28. (Active patent.)
4. Asanov A., Zepeda A., and Vaca L. “A Platform for Combined DNA and Protein Microarrays Based on Total Internal Reflection Fluorescence.” Sensors, 2012, 12, 1800.
5. Patents pending 2016-2017.
6. Willoughby D., Everett K., Halls M., Pacheco J., Skroblin P., Vaca L., Klussmann E., and Cooper D. “Direct Binding Between Orai1 and AC8 Mediates Dynamic Interplay Between Ca2+ and cAMP Signaling.” Science Signaling, 2012, 5 (219), 29.
7. Sampieri A., Zepeda A., Asanov A., and Vaca L. “Visualizing the store operated channel complex assembly in real time: Identification of SERCA2 as a new member.” Cell Calcium, 2009, 45, 439.
8. Asanov A., Zepeda A., and 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, 1801, 147.
9. Asanov A, Sherry R, Sampieri A, and Vaca L. “A relay mechanism between EB1 and APC facilitate STIM1 puncta assembly at endoplasmic reticulum plasma membrane junctions”. Cell Calcium, 2013, 54, 246– 256
10. Luz-Madrigal A, Asanov A, Camacho-Zarco AR, Sampieri A, and Vaca L. “A Cholesterol Recognition Amino Acid Consensus Domain in GP64 Fusion Protein Facilitates Anchoring of Baculovirus to Mammalian Cells”. Journal of Virology, 2013, 87 (2), 11894–11907.
11. Additional publications of our customers with data generated by our TIRF and TIRF-EC products are available at the URL: www.tirf-labs.com
iDiagnostics - The Cellphone Future of Precision Medicine