Interferometric Reflection Imaging Sensor from Multiplexed Molecular Affinity Measurements to Counting Single Analytes

Interferometric reflectance imaging sensor (iRiS) technology is based on interference of light from an optically transparent thin film —the same phenomenon that gives rainbow colors to a soap film when illuminated by white light. IRIS has two modalities [1]: (i) low-magnification (ensemble biomolecular mass measurements) allowing for multiplexed affinity measurements and (ii) high-magnification (digital detection of individual nanoparticles).

iRiS defies the conventional wisdom that calls for enhancing the signal through complex optical resonances. Instead, we exploit light interference and the power of signal averaging in shot-noise-limited operation to achieve virtually unlimited sensitivity in a simple platform. By design, iRiS technique is resilient to the bulk effect, and we devised a new proprietary technique based on creating an illumination spectrum for which the total reflectance intensity does not depend on the index variations of the analyte solution thus virtually eliminating this Achille’s Heel of LFD [2]. Applications of IRIS are broad. In ensemble detections modality, applications include label-free affinity characterization of proteins [2], peptides [3], and small molecular weight analytes [4], and measurement of single nucleotide polymorphism [5]. In single-particle detection modality for biomarker analysis is (or digital detection), IRIS provides resolution and sensitivity beyond the reach of ensemble measurements [7,8]. In vitro tests are a cornerstone of clinical practice, with the sensitivity of standard immunoassays measuring protein biomarkers at picomolar concentrations. This level of sensitivity is sufficient for the diagnosis of infectious diseases when clear symptoms are present, however it falls short significantly for the detection of molecular biomarkers that are important in cancer, neurological disorders, and the early stages of infection as well as environmental sensing. IRIS provides excellent sensitivity in bacteria detection (<10CFU/ml) [9] and virus detection (<50PFU/ml) [10] and demonstrated to exceed the sensitivity of reaction limits through dynamic tracking of single binding events [11].

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