Targeted DNA sequencing and in situ mutation analysis using mobile phone microscopy

Abstract

Molecular diagnostics is typically outsourced to well-equipped centralized laboratories, often far from the patient. We developed molecular assays and portable optical imaging designs that permit on-site diagnostics with a cost-effective mobile-phone-based multimodal microscope. We demonstrate that targeted next-generation DNA sequencing reactions and in situ point mutation detection assays in preserved tumour samples can be imaged and analysed using mobile phone microscopy, achieving a new milestone for tele-medicine technologies.

Mobile Phones Create new Opportunities for Microbiology Research and Clinical Applications

“…Smartphone-based fluorescence microscopes have also been used for imaging nano-sized biological specimen [13,15,16]. In the design of these microscopes, a laser diode-based illumination with a highly-oblique incidence angle (e.g., ∼75°) is used for excitation of target fluorescent tags and particles, which provides a strong rejection of the excitation beam due to the low numerical aperture of the mobile phone camera system.…”

“…In fact, mobile phone-based imaging and sensing platforms have already been used in a variety of applications, including clinical chemistry, biomedical and environmental monitoring [3][4][5], food analysis [6][7][8], detection of different types of chemical and biological analytes such as cells, parasites [9], bacteria [10], eggs [11], proteins [12], various biomarkers [6,7], nanoparticles [13] and even nucleic acids [14][15][16]. In many of these platforms, processing of the acquired data and the resulting computational analysis are done either on the smartphone or over a local or remote server using a customdeveloped smartphone application.…”

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KEYWORDSTogether with their cost-effectiveness, wide-spread use, computational power and connectivity, mobile phones have the potential to transform traditional uses of imaging, sensing and diagnostic systems, especially for point-of-care applications and field settings.In fact, mobile phone-based imaging and sensing platforms have already been used in a variety of applications, including clinical chemistry, biomedical and environmental monitoring [3][4][5], food analysis [6][7][8] [12], various biomarkers [6,7], nanoparticles [13] and even nucleic acids [14][15][16]. In many of these platforms, processing of the acquired data and the resulting computational analysis are done either on the smartphone or over a local or remote server using a customdeveloped smartphone application.

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Microdevices for Non-Invasive Detection of Bladder Cancer

“…By enabling doctors to take unobtrusive, straightforward measurements of patient physiology, such technologies have brought medical monitoring into patients' daily lives for long-term, continuous observation of individual medical cases. Commercially available wearable sensors provide near-instant readouts on parameters such as heart rate, temperature, and oxygen saturation in a user-friendly manner [120]; even more directly relevant to bladder cancer microfluidic devices are phone-based sensors with functionalities such as calculating quantitative ELISA assay results [121] and detecting point mutations in tumor samples [122]. At a deeper level, wearable and phone-based sensors point to further guiding principles in the development of microfluidic devices to assay bladder cancer: the importance of designing devices that are compatible with hospitals' pre-existing equipment and with patients' daily regimens.…”

Smartphone confocal microscopy for imaging cellular structures in human skin in vivo

“…When biopsy-based histopathologic analysis is employed, histopathologic diagnosis takes several weeks to complete, which leads to delay or failure in initiating adequate treatment. Recently, several smartphone-based microscopy technologies have been developed to address clinical challenges in LMICs [3][4][5][6]. Most of these technologies, however, still require tissue collection and slide preparation, which remains a challenging task in many LMICs.…”