Smartphone biosensor

#Since their introduction in 1997, “smartphones” have gained rapid market acceptance. Smartphones provide the user with advanced features in addition to being able to make voice calls. For example, smartphones typically have internet connectivity, high resolution cameras and touch-screen displays, and powerful CPUs. The rapid acceptance of smartphones has been driven by a combination of falling prices and increasingly sophisticated features. In addition, there is a growing ecosystem of applications that take advantage of smartphones' sensors, displays, and ability to connect to powerful computing and data storage capabilities that are available in the “cloud.” The built-in capabilities of smartphones can be further extended through the addition of accessories that enable the phone to sense different types of information. For example, it is already possible to find commercial lens systems that enable the phone to be used as a rudimentary microscope with a 350× magnification, which is sufficient for capturing images of cells, bacteria, and biological tissue. Breslauer et al., Plos One, vol. 4, Jul. 22, 2009 and Smith et al., Plos One, vol. 6, Mar. 2, 2011. Smith et al. also demonstrated that, with addition of a light collimation system and a diffraction grating in front of the camera, a smartphone may function as a spectrometer with a wavelength resolution of 5 nm. The ability of a smartphone camera to take images of the colored label components of a biological assay have been applied to lateral flow immunoassays (Mudanyali et al., Lab Chip, vol. 12, pp. 2678-86, 2012), quantum-dot labeling of bacteria (Zhu et al., Analyst, vol. 137, pp. 2541-2544, 2012), and fluorescence microscopy (Breslauer et al.). Further, smartphone cameras have recently been exploited for microfluidic and optofluidic applications (Martinez et al, Analytical Chemistry, vol. 80, pp. 3699-3707, May 15, 2008 and Zhu et al., Analytical Chemistry, vol. 83, pp. 6641-6647, Sep. 1, 2011) and as a lens-free microscopy tool (Tseng et al., Lab on a Chip, vol. 10, pp. 1787-1792, 2010).

#Such approaches, however, have not involved biomolecular assays with label-free detection. Detection of an analyte through one of its intrinsic physical properties (e.g., dielectric permittivity, mass, conductivity, or Raman scattering spectrum), called “label-free” detection, can be preferable for assay simplicity in terms of the number of reagents required, washing steps needed, and assay time Of all the label-free detection approaches that have been demonstrated, those based upon optical phenomena have been most commercially accepted due to a combination of sensitivity, sensor cost, detection system robustness, and high throughput. Adsorption of biomolecules, viral particles, bacteria, or cells on the surface of an optical biosensor transducer results in a shift in the conditions of optimal optical coupling, which can be measured by illuminating the transducer surface, and subsequently measuring a property of the reflected or transmitted light. Such a detection approach is extremely robust, and has become economically advantageous due to the advent of low cost light emitting diodes (LEDs), semiconductor lasers, and miniature spectrometers. For example, surface plasmon resonance (SPR) based biosensors and photonic crystal (PC) optical biosensors are capable of detecting broad classes of biological analytes through their intrinsic dielectric permittivity. Each approach has been implemented in the form of large laboratory instruments and miniaturized (shoebox-sized) systems. However, no prior label-free optical biosensor instrument has been fully integrated with a smartphone, using the camera in the phone itself as the detection instrument.

#In a first aspect, example embodiments provide a system comprising a light source, an optical assay medium configured to perform a biomolecular assay and provide an optical output in response to light form the light source, wherein the optical output is indicative of a result of the biomolecular assay, a wavelength-dispersive element, and a mobile computing device. The wavelength-dispersive element is configured to disperse the optical output into spatially-separated wavelength components. The mobile computing device includes an image sensor configured to receive at least a portion of the dispersed optical output such that different wavelength components are received at different locations on the image sensor.

#FIG. 1A is a cross-sectional schematic view of an example photonic crystal (PC) structure.

#FIG. 1B is a diagram that illustrates the operating principle of a PC according to an example embodiment.

#FIG. 2A is a schematic diagram showing the optical components of an example smartphone detection system.

#1. Overview

#A mobile computing device (e.g., a smartphone) that includes an image sensor can be used as the detection instrument for various types of biomolecular assays. Such biomolecular assays may involve the qualitative or quantitative detection of DNA, RNA, nucleotides, proteins, or any other biologically relevant molecules. In an example embodiment, the mobile computing device is mounted to a special-purpose cradle that holds one or more optical components in alignment with the image sensor. With the mobile computing device properly mounted, the image sensor can be used to obtain one or more images from which the wavelength spectrum of an optical output of a biomolecular assay can be determined. In this way, the image sensor of a mobile computing device can perform the function of a high resolution spectrometer and wavelength filter.

#The biomolecular assay may be performed in an optical assay medium that is illuminated using either a light source on the mobile computing device, such as a light emitting diode (LED), or an external light source, such as a light bulb, LED, or laser. In response to this illumination, the optical assay medium provides an optical output with a wavelength spectrum that can be detected by the image sensor on the mobile computing device. For example, a diffraction grating or other wavelength-dispersive element may be used to disperse the optical output into spatially-separated wavelength components such that different wavelength components are received at different locations on the image sensor.