Imaging and Sizing of Single DNA Molecules on a Mobile Phone

Abstract

DNA imaging techniques using optical microscopy have found numerous applications in biology, chemistry and physics and are based on relatively expensive, bulky and complicated set-ups that limit their use to advanced laboratory settings. Here we demonstrate imaging and length quantification of single molecule DNA strands using a compact, lightweight and cost-effective fluorescence microscope installed on a mobile phone. In addition to an optomechanical attachment that creates a high contrast dark-field imaging setup using an external lens, thin-film interference filters, a miniature dovetail stage and a laser-diode for oblique-angle excitation, we also created a computational framework and a mobile phone application connected to a server back-end for measurement of the lengths of individual DNA molecules that are labeled and stretched using disposable chips. Using this mobile phone platform, we imaged single DNA molecules of various lengths to demonstrate a sizing accuracy of <1 kilobase-pairs (kbp) for 10 kbp and longer DNA samples imaged over a field-of-view of ∼2 mm2.

Cellphone-based diagnostic devices

“…Cellphones especially outweigh over others in terms of their convenience in myriad situations in mundane life. It is no wonder that researchers have pursued their use as compelling measurement devices for examination, data collection, and transmission in and from remote and resource-limited settings [24][25][26][27]. When it comes to health care exploration, cellphones may bridge existing gaps between patients and timely, affordable healthcare, especially in more remote regions.…”

“…CMOS image sensors mainly consist of a pixel sensor array (detection wavelengths: 380-1100 nm) and optical filters, and are primarily used for capturing images under the visible spectrum and in the presence of ultraviolet (UV) and infrared (IR) filters [27]. Color information is processed by band-pass filters that transmit either blue, green, or red light on the pixel array; Bayer mosaic, a repetitive 2 × 2 grid with one red filter, two green filters, and one blue filter per four pixels, is a typical pattern of color filters in CMOS image sensors [28].…”

“…Color information is processed by band-pass filters that transmit either blue, green, or red light on the pixel array; Bayer mosaic, a repetitive 2 × 2 grid with one red filter, two green filters, and one blue filter per four pixels, is a typical pattern of color filters in CMOS image sensors [28]. CMOS image sensors can achieve more than 40 megapixel image resolution [27].…”

“…The development of cellphone-based microscopy is intertwined with advances in lens attachment-based microscopy and lens-free holographic microscopy [27,29]. In 2009, Prof. Fletcher's group at UC Berkeley demonstrated the prototype of cellphone-based microscopy with a light lens attachment (~ 15 cm long) that could be used for global health applications ( Figure 1A) [29].…”

Smartphone-based low light detection for bioluminescence application

“…In addition, compared to other laboratory equipment, smartphones are inexpensive and can be easily converted to portable instruments with appropriate accessories. Numerous smartphone-based analytical devices have been previously reported including: spectrometers12, microscopes1345, fluorimeters6789, colorimetric devices101112, and instruments for immunochemistry13 and microbiology14. Luminescence detection by mobile phones include a bio-luminescence assay to detect bile acid and chemo-luminescence assays for cholesterol detection15, lactate in oral fluid16, and salivary cortisol level17.…”