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===Interferometric reflectance imaging sensor=== The interferometric reflectance imaging sensor (IRIS) is based on the principles of [[Interference (wave propagation)|optical interference]] and consists of a silicon-silicon oxide substrate, standard optics, and low-powered coherent LEDs. When light is illuminated through a low magnification objective onto the layered silicon-silicon oxide substrate, an interferometric signature is produced. As biomass, which has a similar [[index of refraction]] as silicon oxide, accumulates on the substrate surface, a change in the interferometric signature occurs and the change can be correlated to a quantifiable mass. ''Daaboul et al.'' used IRIS to yield a label-free sensitivity of approximately 19 ng/mL.<ref>{{cite journal | last1 = Daaboul | first1 = G.G. | display-authors = etal | year = 2010 | title = LED-based Interferometric Reflectance Imaging Sensor for quantitative dynamic monitoring of biomolecular interactions| journal = Biosens. Bioelectron. | volume = 26| issue = 5| pages = 2221–2227| doi = 10.1016/j.bios.2010.09.038 | pmid = 20980139 }}</ref> ''Ahn et al.'' improved the sensitivity of IRIS through a mass tagging technique.<ref>{{cite journal | last1 = Ahn | first1 = S. | last2 = Freedman | first2 = D. S. | last3 = Massari | first3 = P. | last4 = Cabodi | first4 = M. | last5 = Ünlü | first5 = M. S. | year = 2013 | title = A Mass-Tagging Approach for Enhanced Sensitivity of Dynamic Cytokine Detection Using a Label-Free Biosensor | journal = Langmuir | volume = 29 | issue = 17| pages = 5369–5376 | doi=10.1021/la400982h| pmid = 23547938 }}</ref> Since initial publication, IRIS has been adapted to perform various functions. First, IRIS integrated a fluorescence imaging capability into the interferometric imaging instrument as a potential way to address fluorescence protein microarray variability.<ref>{{cite journal | last1 = Reddington | first1 = A. | last2 = Trueb | first2 = J. T. | last3 = Freedman | first3 = D. S. | last4 = Tuysuzoglu | first4 = A. | last5 = Daaboul | first5 = G. G. | last6 = Lopez | first6 = C. A. | last7 = Karl | first7 = W. C. | last8 = Connor | first8 = J. H. | last9 = Fawcett | first9 = H. E. | last10 = Ünlü | first10 = M. S. | year = 2013 | title = An Interferometric Reflectance Imaging Sensor for Point of Care Viral Diagnostics | journal = IEEE Transactions on Biomedical Engineering | volume = 60 | issue = 12| pages = 3276–3283 | doi=10.1109/tbme.2013.2272666| pmid = 24271115 | pmc = 4041624 }}</ref> Briefly, the variation in fluorescence microarrays mainly derives from inconsistent protein immobilization on surfaces and may cause misdiagnoses in allergy microarrays.<ref name="ReferenceA">{{cite journal | last1 = Monroe | first1 = M. R. | last2 = Reddington | first2 = A. | last3 = Collins | first3 = A. D. | last4 = Laboda | first4 = C. D. | last5 = Cretich | first5 = M. | last6 = Chiari | first6 = M. | last7 = Little | first7 = F. F. | last8 = Ünlü | first8 = M. S. | year = 2011 | title = Multiplexed method to calibrate and quantitate fluorescence signal for allergen-specific IgE | journal = Analytical Chemistry | volume = 83| issue = 24| pages = 9485–9491| doi=10.1021/ac202212k | pmid=22060132 | pmc=3395232}}</ref> To correct for any variation in protein immobilization, data acquired in the fluorescence modality is then normalized by the data acquired in the label-free modality.<ref name="ReferenceA"/> IRIS has also been adapted to perform single [[nanoparticle]] counting by simply switching the low magnification objective used for label-free biomass quantification to a higher objective magnification.<ref>{{cite journal | last1 = Yurt | first1 = A. | last2 = Daaboul | first2 = G. G. | last3 = Connor | first3 = J. H. | last4 = Goldberg | first4 = B. B. | last5 = Ünlü | first5 = M. S. | year = 2012 | title = Single nanoparticle detectors for biological applications | journal = Nanoscale | volume = 4 | issue = 3| pages = 715–726 | doi=10.1039/c2nr11562j| pmid = 22214976 | pmc = 3759154 |bibcode = 2012Nanos...4..715Y }}</ref><ref>C. A. Lopez, G. G. Daaboul, R. S. Vedula, E. Ozkumur, D. A. Bergstein, T. W. Geisbert, H. Fawcett, B. B. Goldberg, J. H. Connor, and M. S. Ünlü, "Label-free multiplexed virus detection using spectral reflectance imaging," Biosensors and Bioelectronics, 2011</ref> This modality enables size discrimination in complex human biological samples. ''Monroe et al.'' used IRIS to quantify protein levels spiked into human whole blood and serum and determined allergen sensitization in characterized human blood samples using zero sample processing.<ref>{{cite journal | last1 = Monroe | first1 = M. R. | last2 = Daaboul | first2 = G. G. | last3 = Tuysuzoglu | first3 = A. | last4 = Lopez | first4 = C. A. | last5 = Little | first5 = F. F. | last6 = Ünlü | first6 = M. S. | year = 2013 | title = Single Nanoparticle Detection for Multiplexed Protein Diagnostics with Attomolar Sensitivity in Serum and Unprocessed Whole Blood | journal = Analytical Chemistry | volume = 85 | issue = 7| pages = 3698–3706 | doi=10.1021/ac4000514 | pmid=23469929 | pmc=3690328}}</ref> Other practical uses of this device include virus and pathogen detection.<ref>{{cite journal | last1 = Daaboul | first1 = G. G. | last2 = Yurt | first2 = A. | last3 = Zhang | first3 = X. | last4 = Hwang | first4 = G. M. | last5 = Goldberg | first5 = B. B. | last6 = Ünlü | first6 = M. S. | year = 2010 | title = High-Throughput Detection and Sizing of Individual Low-Index Nanoparticles and Viruses for Pathogen Identification | journal = Nano Letters | volume = 10| issue = 11| pages = 4727–4731 | doi=10.1021/nl103210p | pmid=20964282| bibcode = 2010NanoL..10.4727D }}</ref>
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