Microscopy and mobile phones
The functions of the traditional light microscope are being augmented by the mobile phone.
Modern technology is turning the cameras of mobile phones into high-quality light microscopes with the added benefits of automation and wireless communication, facilitating remote-area point-of-care diagnoses and enhancing classroom education.
Mobile phone video microscope detects parasitic worms
Scientists from the National Institute of Allergy and Infectious Diseases, the University of California Berkeley and colleagues have developed a mobile phone microscope to measure blood levels of the parasitic filarial worm Loa loa. The point-of-care device may enable safe resumption of mass drug administration campaigns to eradicate the parasitic diseases onchocerciasis (river blindness) and lymphatic filariasis (elephantiasis).
Efforts to eliminate these diseases in Central Africa through community-wide administration of antiparasitic drugs have been suspended due to potentially fatal drug-associated side effects in people with high blood levels of Loa microfilariae, the filarial worm’s larval form. A potential solution is to identify and exclude such people from mass drug administration. However, standard methods for measuring microfilariae are time consuming and must be performed by trained personnel with laboratory equipment.
To rapidly screen for Loa infections in community settings, the scientists developed CellScope Loa, a video microscope integrating an Apple iPhone 5s.
CellScope Loa pairs a smartphone with a 3D-printed plastic base where the sample of blood is positioned. The base includes LED lights, microcontrollers, gears, circuitry and a USB port.
Control of the device is automated through an app the researchers developed for this purpose. With a single touch of the screen by the healthcare worker, the phone communicates wirelessly via Bluetooth to controllers in the base to process and analyse the sample of blood. Gears move the sample in front of the camera and an algorithm automatically analyses the telltale ‘wriggling’ motion of the worms in video captured by the phone. The worm count is then displayed on the screen.
The researchers found that using motion instead of molecular markers or fluorescent stains to detect the movement of worms was as accurate as conventional screening methods.
The procedure takes about two minutes or less, starting from the time the sample is inserted to the display of the results. Pricking a finger and loading the blood onto the capillary adds an additional minute to the time. No special preparation of the blood is required, limiting potential error and sample loss, and healthcare workers need minimal training to use the automated device.
Screening of blood samples from potentially Loa-infected people under field conditions in Cameroon, Africa, showed that CellScope Loa results correspond well to those obtained by standard methods, correctly identifying people with microfilarial levels over a certain threshold. Although additional work is needed to prepare the technology for broad use, the researchers predict that a team of three workers could screen up to 200 people during the four-hour midday window when Loa circulates at its peak in the blood.
Turn your smartphone into a DNA-scanning fluorescent microscope
Researchers at the University of California, Los Angeles (UCLA) have recently developed a device that can turn any smartphone into a DNA-scanning fluorescent microscope that can image and size DNA molecules 50,000 times thinner than a human hair.
“A single DNA molecule, once stretched, is about two nanometres in width,” said Aydogan Ozcan, HHMI Chancellor Professor, UCLA. “For perspective, that makes DNA about 50,000 times thinner than a human hair. Currently, imaging single DNA molecules requires bulky, expensive optical microscopy tools, which are mostly confined to advanced laboratory settings. In comparison, the components for my device are significantly less expensive.”
Enter Ozcan’s smartphone attachment - an external lens, a thin-film interference filter, a miniature dovetail stage mount for making fine alignments and a laser diode, all enclosed in a small, 3D-printed case and integrated to act just like a fluorescence microscope.
Although other smartphone-turned-microscopes can image larger scale objects such as cells, Ozcan’s group’s latest mobile phone optical attachment is the first to image and size the slim strand of a single DNA molecule.
The device is intended for use in remote laboratory settings to diagnose various types of cancers and nervous system disorders, as well as to detect drug resistance in infectious diseases. To use the camera, it is necessary to first isolate and label the desired DNA with fluorescent tags. Ozcan says such laboratory procedures are possible even in remote locations and resource-limited settings.
To scan the DNA, the group developed a computational interface and Windows smart application running on the same smartphone. The scanned information is then sent to a remote server in Ozcan’s laboratory, which measures the length of the DNA molecules. Assuming you have a reliable data connection, the entire data processing takes less than 10 seconds.
In their lab, Ozcan’s group tested the device’s accuracy by imaging fluorescently labelled and stretched DNA segments. It reliably sized DNA segments of 10,000 base pairs or longer. Many important genes fall in this size range - including a bacterial gene notorious for giving Staphylococcus aureus and other bacteria antibiotic resistance, which is about 14,000 base pairs long.
The smartphone microscope demonstrated a significant drop in accuracy for 5000 base-pair or shorter segments, however, due to the reduced detection signal-to-noise ratio and contrast for such short fragments. The problem could easily be remedied by replacing the device's current lens with one of a higher numerical aperture, Ozcan said.
In addition to its use in point-of-care diagnostics, Ozcan proposes that his platform could also be useful for differentiating high-molecular-weight DNA fragments, which are problematic for conventional gel electrophoresis - a frequently used technique in biochemistry and molecular biology to size DNA and RNA fragments. Ozcan’s group next plans to test their device in the field to detect the presence of malaria-related drug resistance.
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