Dramatic improvements in light-activated fluorescent dyes for disease diagnosis and more

Sophia and Richard Lunt detect and attack cancer cells using technology traditionally reserved for solar power. They made dramatic improvements in light-activated fluorescent dyes for disease diagnosis, image-guided surgery and site-specific tumor treatment. Courtesy of MSU

Scientific breakthroughs don’t always happen in labs. For Sophia and Richard Lunt, Michigan State University researchers, many of their breakthroughs happen during neighborhood walks.

The married couple’s step-by-step approach has revealed a new way to detect and attack cancer cells using technology traditionally reserved for solar power. The results, published in the current issue of Scientific Reports, showcases dramatic improvements in light-activated fluorescent dyes for disease diagnosis, image-guided surgery and site-specific tumor treatment.

“We’ve tested this concept in breast, lung cancer and skin cancer cell lines and mouse models, and so far it’s all looking remarkably promising,” said Sophia, MSU biochemistry and molecular biologist.

While the cancer applications hold the most possibility, their findings have potential beyond the field of oncology, said Richard, the Johansen Crosby Endowed Professor of chemical engineering and materials science.

“This work has the potential to transform fluorescent probes for broad societal impact through applications ranging from biomedicine to photocatalysis – the acceleration of chemical reactions with light,” he said. “Our solar research inspired this cancer project, and in turn, focusing on cancer cells has advanced our solar cell research; it’s been an amazing feedback loop.”

Prior to the Lunts’ combined effort, fluorescent dyes used for therapeutics and diagnostics, aka “theranostics,” had shortcomings, such as low brightness, high toxicity to cells, poor tissue penetration and unwanted side effects.

By optoelectronically tuning organic salt nanoparticles used as theranostics, the Lunts were able to control them in a range of cancer studies. Coaxing the nanoparticles into the nontoxic zone resulted in enhanced imaging, while pushing them into the phototoxic – or light-activated – range produced effective on-site tumor treatment.

The key was learning to control the electronics of their photoactive molecules independently from their optical properties and then making the leap to apply this understanding in a new way to a seemingly unrelated field.

Richard had recently discovered the ability to electronically tune these salts from his work in converting photovoltaics into solar glass.

Sophia had long studied metabolic pathways unique to cancer cells. It was when the Lunts were discussing solar glass during a walk that they made the connection: Molecules active in the solar cells might also be used to more effectively target and kill cancer cells.

A journey of 1,000 miles

Their walks had rather unscientific beginnings. Shortly after the Lunts met at Princeton University, Richard moved to another university. To maintain their long-distance relationship, they scheduled daily phone calls. Upon their arrival at MSU, individual academic career demands replaced geographic distance as a challenge to their busy lives.

To connect daily, they take CEO-style walks together every evening. The two-mile saunters take place rain or shine, and they often engage in scientific discussions. The three keys to their walks are intentional curiosity, perseverance and the merging of different fields and perspectives, Sophia said.

“We talk science, strategic plans for our careers and our various grants,” she said. “We ping ideas off each other. Our continual conversations brainstorming ideas on a particular topic or challenge often lead to those exciting ‘aha’ moments.”

Their walks have helped them push through many challenges.

“Our first experiments did not turn out as expected; I’m surprised that we didn’t give up given how crazy the idea seemed at first,” Richard said. “Figuring out how to do this research took many walks.”

Obviously, the results were worth the hike. Today, Richard designs the molecules; Babak Borhan, MSU chemist, synthesizes and improves them; and Sophia tests their photoactive inventions in cancer cell lines and mouse models.

Future research will work to improve the theranostics’ effectiveness, decrease toxicity and reduce side effects. The Lunts have applied for a patent for their work, and they’re looking forward to eventually pushing their photoactive molecule findings through clinical trials.

“Though that will take many more walks,” Richard said with a smile.

Learn more: CAN SOLAR TECHNOLOGY KILL CANCER CELLS?

 

The Latest on: Theranostics

via Google News

 

The Latest on: Theranostics

via  Bing News

 

Smartphones get artificial intelligence help to diagnose disease

Images of a diagnostic assay are captured using a smartphone camera. Regions of interest are extracted and are converted to HSV (hue, saturation, value) space. After the conversion process, the standard pixel intensity analysis is applied to the saturation channel and the values are used to determine absorbance and concentration of the sample automatically.
CREDIT
Florida Atlantic University

Accessible, connected, and computationally powerful, smartphones aren’t just for “selfies” anymore. They have emerged as powerful evaluation tools capable of diagnosing medical conditions in point-of-care settings. Smartphones also are a viable solution for health care in the developing world because they allow untrained users to collect and transmit data to medical professionals.

Although smartphone camera technology today offers a wide range of medical applications such as microscopy and cytometric analysis, in practice, cell phone image tests have limitations that severely restrict their utility. Addressing these limitations requires external smartphone hardware to obtain quantitative results – imposing a design tradeoff between accessibility and accuracy.

Researchers from Florida Atlantic University’s College of Engineering and Computer Science have developed a novel cell phone imaging algorithm that enables analysis of assays typically evaluated via spectroscopy, a highly sophisticated and powerful device used in scientific research.

Through the analysis of more than 10,000 images, the researchers have been able to demonstrate that the saturation method they developed consistently outperformed existing algorithms under a wide range of operating field conditions. Their findings, published in the journal Analyst of the Royal Society of Chemistry, is a step forward in developing point-of-care diagnostics by reducing the need for required equipment, improving the limit of detection, and increasing the precision of quantitative results.

“Smartphone cameras are optimized for image appearance rather than for quantitative image-based measurements, and they can’t be bypassed or reversed easily. Furthermore, most lab-based biological and biochemical assays still lack a robust and repeatable cell phone analogue,” said Waseem Asghar, Ph.D., lead author and an assistant professor in FAU’s Department of Computer and Electrical Engineering and Computer Science. “We have been able to develop a cell phone-based image preprocessing method that produces a mean pixel intensity with smaller variances, lower limits-of-detection, and a higher dynamic range than existing methods.”

For the study, Asghar and co-authors Benjamin Coleman and Chad Coarsey, graduate students in the Asghar Laboratory in FAU’s College of Engineering and Computer Science, performed image capture using three smartphones: the Android Moto G with a 5 megapixel (MP) camera; the iPhone 6 with a 12 MP camera, and the Samsung Galaxy Edge 7 with a 12 MP camera.

They tested for image capture at various conditions, measured algorithm performance, tested sensitivity to camera distance, tilt and motion, and examined histogram properties and concentration response. They also examined limit-of-detection as well as properties of saturation, ambient lighting levels and relationship with red-green-blue (RGB) color space. Cell phone images are natively stored as arrays of RGB pixel intensities, commonly referred to as color channels.

Using several thousand images, the researchers compared saturation analysis with existing RGB methods and found that it both analytically and empirically improved performance in the presence of additive and multiplicative ambient light noise. They also showed that saturation analysis can be interpreted as an optimized version of existing RGB ratio tests. They verified that the ideal image capture conditions include constant white light, a clean white background, minimal distance to the sample and zero angular displacement of the camera.

Asghar, Coleman and Coarsey also applied the test to an ELISA (enzyme-linked immunosorbent assay), a plate-based assay technique designed for detecting and quantifying substances such as peptides, proteins, antibodies and hormones. They discovered that for HIV, saturation analysis enabled an equipment-free evaluation and a limit-of-detection was significantly lower than what is currently available with RGB methods.

The FAU-developed methodology represents an improvement in repeatability, practicality, and image capture noise rejection. In addition, saturation analysis is not affected by many of the major limiting factors for image-based tests, such as ambient lighting variations, shading, and variable light levels. The researchers anticipate that the favorable properties of saturation analysis will encounter and enable cell phone image-based point-of-care tests with less equipment overhead and lower limits-of-detection.

“The research taking place in the Asghar Laboratory at Florida Atlantic University has important implications for diagnostic medicine and the delivery of health care in developed as well as developing countries,” said Stella Batalama, Ph.D., dean of FAU’s College of Engineering and Computer Science. “Professor Asghar and his team are driven to continue to develop cutting-edge technology that has the ability to remotely detect and diagnose diseases rapidly, accurately and inexpensively. This latest algorithm they have developed is one of the many advances they are making in this field.”

Learn more: Selfies to self-diagnosis: Algorithm ‘amps up’ smartphones to diagnose disease

 

 

The Latest on: Smartphone disease diagnostics

via Google News

 

The Latest on: Smartphone disease diagnostics

via  Bing News

 

Quick, accurate, and inexpensive screening of diseases with new test kit

A multidisciplinary team at NUS BIGHEART has developed enVision – a portable, easy-to-use and inexpensive device for quick and accurate screening of diseases.

Test results are denoted by a colour change and could be further analysed by a smartphone app, making it attractive as a point-of-care diagnostic device 

A multidisciplinary team of researchers at the National University of Singapore (NUS) has developed a portable, easy-to-use device for quick and accurate screening of diseases. This versatile technology platform called enVision (enzyme-assisted nanocomplexes for visual identification of nucleic acids) can be designed to detect a wide range of diseases – from emerging infectious diseases (e.g. Zika and Ebola) and high-prevalence infections (e.g. hepatitis, dengue, and malaria) to various types of cancers and genetic diseases.

enVision takes between 30 minutes to one hour to detect the presence of diseases, which is two to four times faster than existing infection diagnostics methods. In addition, each test kit costs under S$1 – 100 times lower than the current cost of conducting similar tests.

“The enVision platform is extremely sensitive, accurate, fast, and low-cost. It works at room temperature and does not require heaters or special pumps, making it very portable. With this invention, tests can be done at the point-of-care, for instance in community clinics or hospital wards, so that disease monitoring or treatment can be administered in a timely manner to achieve better health outcomes,” said team leader Assistant Professor Shao Huilin from the Biomedical Institute for Global Health Research and Technology (BIGHEART) and Department of Biomedical Engineering at NUS. Asst Prof Shao is also an investigator with the Institute of Molecular and Cell Biology (IMCB) under the Agency for Science, Technology and Research (A*STAR).

via NUS

Superior sensitivity and specificity compared to clinical gold standard

The research team used the human papillomavirus (HPV), the key cause of cervical cancer, as a clinical model to validate the performance of enVision. In comparison to clinical gold standard, this novel technology has demonstrated superior sensitivity and specificity.

enVision is not only able to accurately detect different subtypes of the same disease, it is also able to spot differences within a specific subtype of a given disease to identify previously undetectable infections,” Asst Prof Shao added.

Bringing the lab to the patient

In addition, test results are easily visible – the assay turns from colourless to brown if a disease is present – and could also be further analysed using a smartphone for quantitative assessment of the amount of pathogen present. This makes enVision an ideal solution for personal healthcare and telemedicine.

“Conventional technologies – such as tests that rely on polymerase chain reaction to amplify and detect specific DNA molecules – require bulky and expensive equipment, as well as trained personnel to operate these machines. With enVision, we are essentially bringing the clinical laboratory to the patient. Minimal training is needed to administer the ,test and interpret the results, so more patients can have access to effective, lab-quality diagnostics that will substantially improve the quality of care and treatment,” said Dr Nicholas Ho, a researcher from NUS BIGHEART and A*STAR’s IMCB, and co-first author of the study.

Versatile point-of-care diagnostic device

In this study, Asst Prof Shao and her team developed patented DNA molecular machines that can recognise genetic material of different diseases and perform different functions. These molecular machines form the backbone of the enVision platform.

The novel platform adopts a ‘plug-and-play’ modular design and uses microfluidic technology to reduce the amount of samples and biochemical reagents required as well as to optimise the technology’s sensitivity for visual readouts.

“The enVision platform has three key steps – target recognition, target-independent signal enhancement, and visual detection. It employs a unique set of molecular switches, composed of enzyme-DNA nanostructures, to accurately detect, as well as convert and amplify molecular information into visible signals for disease diagnosis,” explained Dr Lim Geok Soon, a researcher from NUS BIGHEART and A*STAR’s IMCB, and co-first author of the study.

Each test is housed in a tiny plastic chip that is preloaded with a DNA molecular machine that is designed to recognise disease-specific molecules. The chip is then placed in a common signal cartridge that contains another DNA molecular machine responsible for producing visual signals when disease-specific molecules are detected.

Multiple units of the same test chip – to test different patient samples for the same disease – or a collection of test chips to detect different diseases could be mounted onto the common cartridge.

“Having a target-independent signal enhancement step frees up the design possibilities for the recognition element. This allows enVision to be programmed as a biochemical computer with varying signals for different combinations of target pathogens. This can be very useful to monitor populations for multiple diseases like dengue and malaria simultaneously, or testing for highly mutable pathogens like the flu with high sensitivity and specificity,” said Dr Ho.

Future work

Asst Prof Shao and her team took about a year and a half to develop the enVision platform. Building on the current work, the research team is developing a sample preparation module – for extraction and treatment of DNA material – to be integrated with the enVision platform to enhance point-of-care application. In addition, the research team foresees that the smartphone app could include more advanced image correction and analysis algorithms to further improve its performance for real-world application.

This research work was published in prestigious scientific journal Nature Communications in August 2018, and featured as an Editors’ Highlight by the journal.

Learn more: New test kit invented by NUS researchers enables quick, accurate, and inexpensive screening of diseases

 

 

The Latest on: Disease diagnostic tool

via Google News

 

The Latest on: Disease diagnostic tool

via  Bing News

 

Using tiny micromotors to diagnose and treat disease in the human body

These pills could soon be used to deliver tiny micromotors in the human body.
Credit: American Chemical Society

Using tiny micromotors to diagnose and treat disease in the human body could soon be a reality.

But keeping these devices intact as they travel through the body remains a hurdle. Now in a study appearing in ACS Nano, scientists report that they have found a way to encapsulate micromotors into pills. The pill’s coating protects the devices as they traverse the digestive system prior to releasing their drug cargo.

About the width of a human hair, micromotors are self-propelled microscopic robots designed to perform a host of biomedical tasks. In previous research, Joseph Wang, Liangfang Zhang and colleagues used micromotors coated with an antibiotic to treat ulcers in laboratory mice. They found that this approach produced better results than just taking the drugs by themselves. However, the researchers noted that body fluids, such as gastric acid and intestinal fluids, can compromise the effectiveness of micromotors and trigger early release of their payloads. In addition, when taken orally in fluid, some of the micromotors can get trapped in the esophagus. To overcome these issues, Wang and Zhang sought to develop a way to protect and carry these devices into the stomach without compromising their mobility or effectiveness.

The researchers created a pill composed of a pair of sugars — lactose and maltose — that encapsulated tens of thousands of micromotors made of a magnesium/titanium dioxide core loaded with a fluorescent dye cargo. These sugars were chosen because they are easy to mold into tablet, can disintegrate when needed and are nontoxic. When given to laboratory mice, these pills improved the release and retention of the micromotors in the stomach compared to those encapsulated in silica-based tablets or in a liquid solution. The researchers concluded that encapsulating micromotors in traditional pill form improves their ability to deliver medicines to specific targets without diminishing their mobility or performance.

Learn more: A pill for delivering biomedical micromotors

 

 

The Latest on: Micromotors

via Google News

 

The Latest on: Micromotors

via  Bing News

 

A simple test that can quickly and cheaply identify whether a mosquito belongs to the species that carries dangerous diseases

The tool uses a smartphone camera, a small 3D-printed box and a simple chemical test to show whether a dead mosquito belongs to the Aedes aegypti species. Vivian Abagiu

A new diagnostic tool has been developed by researchers at The University of Texas at Austin that can easily, quickly and cheaply identify whether a mosquito belongs to the species that carries dangerous diseases such as Zika virus, dengue, chikungunya or yellow fever.  It can also determine whether the bug has come into contact with a mosquito-control strategy known as Wolbachia.

“Many of these diseases are spreading in areas where they weren’t common before,” said Sanchita Bhadra, a research associate in the Department of Molecular Biosciences and first author on the paper. “Having surveillance is important in conjunction with any kind of outbreak, and this method allows a rapid test in the field.”

The tool uses a smartphone camera, a small 3D-printed box and a simple chemical test to show whether a dead mosquito belongs to the Aedes aegypti species. Aedes aegypti carries Zika and other devastating viruses that afflict an estimated 100 million people worldwide each year. The species also is closely linked to the tripling of cases of mosquito-borne diseases in the United States since 2004.

The research appears in the journal PLOS Neglected Tropical Diseases.

The tool developed by scientists and students at UT Austin also detects the presence of a biopesticide called Wolbachia, a type of bacteria that keeps mosquitoes from spreading diseases. In countries around the world and in 20 U.S. states where the Aedes aegypti mosquito is found, scientists working in public health agencies have started to infect mosquitoes with Wolbachia by introducing the bacteria into a local mosquito population to help curb transmission of viruses.

Because mosquitoes show no outward signs of having the bacteria – and because existing diagnostic tests are hard to read, expensive and logistically cumbersome – the new tool represents a significant step forward for those hoping to monitor the effectiveness of Wolbachia.

“This test can happen without involving a lot of staff and equipment to make sure Wolbachia is effective and spreading as anticipated,” Bhadra said.

Public health groups trap and kill mosquitoes routinely in conjunction with monitoring efforts, but existing technology requires a complex process to extract nucleic acid from inside mosquitoes, often after they have been dead for days and have started to decay, leading to greater expense and the possibility of more errors in lab tests than the new technology.

The new diagnostic tool uses a smartphone’s camera and a simple test that can be done anywhere. It tests mosquitoes’ nucleic acid without requiring a complicated process to remove it. Officially known as a loop-mediated isothermal amplification and oligonucleotide strand displacement, or LAMP OSD, the probe delivers a simple yes-or-no readout on a cellphonewith accuracy of greater than 97 percent.

In addition to the tests to detect mosquito species and Wolbachia, the team also is exploring use of the technology to easily identify whether trapped mosquitoes are carrying Zika, dengue and other pathogens.

Learn more: Simple Test Detects Disease-Carrying Mosquitoes, Presence of Biopesticide

 

 

The Latest on: Disease diagnostic tool

via Google News

 

The Latest on: Disease diagnostic tool

via  Bing News