Hetal Patel BIO 121 A02 Report 06 Mobile Microscope Detects DNA Sequences The main idea of this article is give us knowledge about the technology that A cell phone–based microscope can identify mutations in tumor tissue and image products of DNA sequencing reactions

Hetal Patel
BIO 121 A02
Report 06

Mobile Microscope Detects DNA Sequences

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The main idea of this article is give us knowledge about the technology that A cell phone–based microscope can identify mutations in tumor tissue and image products of DNA sequencing reactions. Researchers have built a microscope that uses the camera on a cell phone to detect fluorescent products of DNA sequencing reactions in cells and tissues, according to a study. The mobile microscope can detect a point mutation in the KRAS gene that occurs in more than 30 percent of colon cancers. The researcher, Mats Nilsson of Stockholm University in Sweden said this study shows that “one can use a very simple imaging device such as the mobile phone to record DNA sequencing reactions,”. The microscope contains two battery-powered lasers for the detection of different fluorophores and a white LED for bright-field imaging. The cell phone’s camera lens and an external lens provide about 2.6× magnification. The 3-D–printed microscopy platform can manipulate sample slides in all three directions. The researchers used sequencing techniques that amplify and fluorescently label copies of a target DNA sequence or transcript—in this case, mutant or wild-type KRAS—in isolated DNA, colon cancer cell lines, and human tumor samples. They then used the cell phone–based microscope to image the resulting sequencing products.
The significance of this device are mutation analysis and DNA sequencing “are fantastic advances that have been brought to clinical sciences,” researcher Aydogan Ozcan of the University of California, Los Angeles, told The Scientist. “But they are restricted to the laboratory scale and obviously not dispersed to resource-poor or resource-limited environments. Sequencing diagnostics are “the gold standard these days in detecting what kind of cancer a patient has, but due to issues with resources and cost they are probably not performed on a day-to-day basis,” Tay added. He said that this mobile microscope could change that by lowering costs. Another advantage of the combination of this microscope and sequencing strategy over other techniques used to analyze mutations is that cells and tissues are intact.
Despite its advantages, the platform does have some limitations. The first one “how feasible these particular techniques are, especially in low resource settings,” Lundin said. Tay said, “Clearly there’s a lot that can be done on the sample preparation side because it still requires a well-trained lab technician to prepare all the samples,”.
Ozcan said that a goal of the team’s ongoing work is to make the technology “more cost-effective and easier to use without much training.”
One possible extension of this technology is the development of assays for sequences other than the KRAS mutation. “This is a platform that can be scaled up to various different cancers for different types of mutation analysis,” Ozcan told The Scientist.

“I think cancer diagnostics is interesting, but where a very simple reader like this would be extremely useful would be in infectious diagnostics in low-resource settings,” said Nilsson.

“This is something we could do on tuberculosis bacteria as well. We could check for mutations in antibiotic resistance genes and then make a simple test to predict which antibiotic treatment would be efficient in a TB tuberculosis patient.”

He added that the platform could also be used for rapid diagnosis during a viral outbreak, no matter where the point of care is. “You could present the analyzed data remotely to the experts, and then that can feed back to the user more or less immediately,” Nilsson said
Needs improvement: Despite its advantages, the platform does have some limitations. One open question is “how feasible these particular techniques are, especially in low resource settings,” Lundin said. He added that while care providers might use the mobile microscope in many different environments, the availability of additional laboratory equipment could limit the feasibility of the targeted mutation analysis techniques.
“Clearly there’s a lot that can be done on the sample preparation side because it still requires a well-trained lab technician to prepare all the samples,” said Tay.
The authors noted that microfluidics could streamline sample preparation, and Nilsson told The Scientistthat the team is already working toward such a solution.
The future: Ozcan said that a goal of the team’s ongoing work is to make the technology “more cost-effective and easier to use without much training.”
One possible extension of this technology is the development of assays for sequences other than the KRAS mutation. “This is a platform that can be scaled up to various different cancers for different types of mutation analysis,” Ozcan told The Scientist.
“I think cancer diagnostics is interesting, but where a very simple reader like this would be extremely useful would be in infectious diagnostics in low-resource settings,” said Nilsson.
“This is something we could do on tuberculosis bacteria as well. We could check for mutations in antibiotic resistance genes and then make a simple test to predict which antibiotic treatment would be efficient in a TB tuberculosis patient.”
He added that the platform could also be used for rapid diagnosis during a viral outbreak, no matter where the point of care is. “You could present the analyzed data remotely to the experts, and then that can feed back to the user more or less immediately,” Nilsson said.
The device, developed by researchers at the California NanoSystems Institute (CNSI) at UCLA and at Sweden’s Stockholm University and Uppsala University, can image and analyze specific DNA sequences and genetic mutations in tumor cells without having to first extract DNA from them.
Generally, DNA analysis requires sending patients’ cell and tissue samples to well-equipped labs, which in many cases are located far away. Researcher Aydogan Ozcan, UCLA’s Chancellor’s Professor of electrical engineering and bioengineering, and associate director of CNSI said this device will ease that burden and decrease costs.

“Our device could make the mutation testing accessible to health care workers even in remote locations, without the need for large, expensive lab equipment,” said Ozcan. “Ultralow-cost DNA sequencing and tumor biopsy analysis can substantially decrease diagnostic costs and make it more widely accessible.”

To use the device, first a technician places a tissue sample in a small container. The mobile phone microscope then records multimode images of the processed sample and subsequently feeds data to an algorithm. This algorithm automatically analyzes the images to read the sequenced DNA bases of the extracted tumor DNA, or to find genetic mutations directly inside the tumor tissue. The device can detect even small amounts of cancer cells among a large group of normal cells.

Ozcan told Photonics Media he and his fellow researchers achieved a new milestone for telemedicine technologies in creating a device that can in fact, image and detect next-generation DNA sequencing reactions.

“More specifically, we showed that a cost-effective and compact multimodal microscope integrated on a mobile phone can be used for targeted DNA sequencing and in situ point mutation analysis that allow integrating molecular analysis with tumor tissue morphology.”

The lightweight optical attachment used with a standard smartphone camera was created using a 3D printer. It is capable of capturing multicolor fluorescence, bright-field and dark-field images of cells, and tissue samples at the same quality of those created by a traditional light microscope.

When Stanford University bioengineer Manu Prakash traveled to a mosquito-infested rainforest in Thailand a couple of years ago, he visited a clinic with a sophisticated, $100,000 microscope that sat unused in a locked room. It was then Prakash realized that what global health workers really need is an ultra-low cost, simple-to-use, portable microscope that could be deployed in the field to diagnose disease—and he took it upon himself to develop one!
The result is the Foldscope, a ‘use and throwaway’ microscope that Prakash demonstrated last week at the first-ever Maker Faire at the White House. While I saw many amazing inventions and met many incredible inventors at this event, I came away particularly impressed by the practicality of this device and the ingenuity of its maker.
Here’s what you need to know about the Foldscope. It’s made out of thick, waterproof paper and a glass-and-polymer lens that’s the size of a large grain of sand. While it can be used by simply holding the device up to the sun or a light bulb, there’s also a version illuminated by tiny LEDs powered by an inexpensive watch battery.
The framework of the Foldscope is printed onto a sheet of paper that’s perforated in a way that each shape can be easily snapped out and folded in a manner resembling the traditional Japanese art of origami. A diagram showing how to assemble the Foldscope is even included on the sheet, and can be understood by anyone, regardless of their native language.
Different designs, folding patterns, and types and numbers of lenses create different types of microscopes: bright field, dark field, fluorescence, and lens-array. A low-magnification microscope costs as little as 50 cents, while a high-mag version is just shy of a dollar.
So, how do you use the Foldscope? It turns out that this bookmark-size device uses the same glass slides that one uses in a regular microscope. So, the preparation of blood or tissue samples remain the same. In the simplest version of the scope, the slide is inserted between the microscope’s paper layers and the user, with a thumb and forefinger grasping either end of the microscope strip, holds the lens close to one eye and flexes the strip to find the target object and bring it into focus. I had the chance to try this at the White House event, and found that learning how to use it is very easy. In more advanced versions, the device can project the image onto a wall or any other flat surface—a great, low-cost tool for educating healthcare workers and others in low-income nations about various infectious diseases.
Prakash is currently fine-tuning Foldscopes so they can be field tested in Ghana, Uganda, Nigeria, and Peru for diagnosis of malaria, microfilariasis, leishmaniasis, schistosomiasis, and sleeping sickness. His team at Stanford is also busy designing Foldscopes to help diagnose 30 other diseases, and drawing up plans for a next generation of Foldscopes that will utilize microfluidic components rather than glass slides—a step that should make sample collection and analysis even easier.
Not only will Foldscope give healthcare workers around the globe better ways to detect, and thereby treat, disease, it will also place magnifying power within the reach of all the world’s students, enabling them to ask and answer a great many scientific questions. To this end, Prakash has launched the Ten Thousand Microscopes Project to entice inquiring minds to beta test these devices and design experiments that can then be compiled into a crowd-sourced microscopy text. Imagine a world in which every kid carries around a 50-cent portable microscope, and brings science out of the lab and into real-world biology.
Already 10,000 citizen scientists from 130 countries have answered the call. Among the ideas: a proposal from a Mongolian farmer who wants to use Foldscope to detect potential pathogens in camel milk. Think about it – what would you do if you had one of these in your pocket?

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