Tag Archives: Australian scientists

Biosensors

Biosensors to shield against deadly epidemics

Featured image above: Macdonald (centre) with colleagues from the Programa de Estudio y Control de Enfermedades Tropicales (PECET) at the Universidad de Antioquia, Colombia

In April 2016, only two months after the World Health Organisation officially declared the Zika virus outbreak a Public Health Emergency of International Concern, a team of Australian experts in tropical medicine and mosquito-transmitted diseases travelled to Brazil and Colombia. 

Among the delegation, arranged by the Australian Trade and Investment Commission, was Associate Professor Joanne Macdonald from the University of the Sunshine Coast (USC) in Queensland. The molecular engineer, who also holds an appointment at Columbia University in New York City, has been developing point-of-care biosensors, similar to take-home pregnancy tests, to diagnose diseases. Importantly, these devices can rapidly detect the genomes of multiple diseases simultaneously, keeping costs down for diagnostic testing in areas where lots of diseases are co-occurring.  

With A$130,000 from the Bill and Melinda Gates Foundation, she and colleagues in Queensland have been working on a proof-of-concept to test mosquitoes for malaria, dengue and chikungunya. The test will also detect the bacterium Wolbachia. When introduced into Aedes aegypti mosquitoes, this potential control agent has been found to prevent viruses, including dengue and Zika, from being transmitted to people. 

Improving diagnosis during epidemics with biosensors

Biosensors
A/Prof Joanne Macdonald (far right) and colleagues observing vaccine and antidote production facilities at the Institute of Butantan, Sao Paulo (Credit: A/Prof Joanne Macdonald)

In Rio de Janeiro, Macdonald heard from local researchers how diagnostic testing labs were overwhelmed by the Zika virus epidemic. Clinics were only testing pregnant women, she was told, and results were taking up to two weeks to be returned. Furthermore, labs were having difficulty distinguishing between Zika and dengue, which are closely related, she says. 

In this environment, Macdonald’s biosensors could be a game-changer. Apart from reagent substances,  which trigger chemical reactions that ‘amplify’ DNA to detectable levels, the tests only require the most basic of lab equipment: a heating block and centrifuge (a piece of laboratory equipment, driven by a motor that spins liquid samples at high speed). This means tests can be easily performed in a doctor’s clinic or hospital with results returned inside an hour. 

“The scientists in Colombia and Brazil wanted the technology right then and there because there was such a dire need with the Zika outbreak,” she says. 

Since the trip, Macdonald has begun working on a test to specifically detect the genetic signature of the Zika virus, eliminating the potential for inconclusive results. Having already developed tests to detect Ebola, Japanese encephalitis, West Nile virus, and Hendra virus, which has killed nearly 100 horses in Australia over the last 23 years, Macdonald is confident it’s within reach.   

In a world where deadly disease vectors are increasingly mobile thanks to global transportation networks, Macdonald’s biosensors could become an important line of defence for future epidemics.  

“If we can provide solutions that allow testing to be done at the point-of-care, rather than in a central lab, that would be a big help,” Macdonald says. 

Macdonald has founded a startup called BioCifer to hold the intellectual property rights and commercialise the various technologies, and is currently working with USC to access the relevant intellectual property. With keen investors already in place, she’s hopeful a diagnostic product – initially for use in veterinary clinics and for research-only purposes – could be just two years away.   

Rapid detection vital to saving lives

Reproducing the detection sensitivity of state-of-the-art labs in a cost-effective, portable device is the ultimate goal of Macdonald’s research, and though it may be a decade away, she is making headway. In December 2015, she and her then PhD student Jia Li reported a world-first milestone in the journal Lab on a Chip, published by the Royal Society of Chemistry. 

They had developed a handheld, pregnancy test-style biosensor, which could detect up to seven different analytes, or theoretical diseases. What’s even more innovative is how the device notifies the end-user of the result: if DNA from a certain disease is detected it will light-up patterns of corresponding molecules or dots, like pixels on a computer screen. 

Inspired by the seven segment displays on digital watches, the dots are arranged to resemble the numbers 0 through 9. It’s the first time a numeric display like this has ever been demonstrated on a paper-based biosensor, known as a lateral flow device, and amazingly, it requires no external power source.

The biosensor “is powered entirely by molecules,” says Macdonald. “We are borrowing from computing, but using molecules instead of computer bits.” 

Programmed molecules play strategy games and make autonomous decisions

In 2006, while at Columbia University full-time, Macdonald and her colleagues built a computer out of DNA molecules. They programmed the DNA, modifying it to respond to stimulus, in order to play the strategy game tic-tac-toe interactively against a human. 

In the future, programmed molecules could be used to develop biological machines that operate inside the body, releasing drugs or insulin autonomously, on demand – something her US-based colleagues are working toward. Macdonald, is harnessing the capability of this technology to more rapidly detect deadly diseases. 

By embedding computing principles in molecules “we can decide whether they will turn on or off depending on the presence of other molecules around them,” she says. “So it’s like a chemical reaction based on logic, the molecules can make decisions on their own without any external inputs. And we pre-program them to do this.” This is how the dots in the biosensor know to light up. 

Biosensors
Macdonald inside a laboratory at the Instituto Colombiano de Medicina Tropical, Medellin, Colombia (Colombian Tropical Medicine Institute)(Credit: A/Prof Joanne Macdonald)

Catching the microbiology bug

A rare illness in high school called coxsackievirus, which affected Macdonald’s heart muscles and prevented her from participating in sport, helped spur a lifelong fascination with disease. After she recovered, her interest blossomed at the University of Queensland. While there she majored in biochemistry and microbiology, and later completed a PhD investigating the West Nile virus under the supervision of immunoassay expert Professor Roy A. Hall, who she is still collaborating with.

Macdonald went on to spend 10 years at Columbia University, first in the lab of  Professor Ian W. Lipkin, an epidemiologist who was the scientific adviser for the Hollywood blockbuster Contagion, and then working with two “humongous scientific minds” in Professors Donald W. Landry and Milan N. Stojanovic. Under their guidance she not only programmed DNA molecules to play tic-tac-toe, but also helped develop a drug that inactivates cocaine, which is now being trialled as a treatment for overdoses. 

Back in Australia since 2012 and focused primarily on rapid disease detection, Macdonald is thinking about the next big question as point-of-care and biosensor technologies advance: “Can we actually predict epidemics before they start?” 

In the future, she wants her biosensors to effectively act as shields, used pre-emptively by aid agencies and community members to screen their surroundings, including potential hosts of infectious diseases such as bats, monkeys and mosquitoes, before outbreaks occur. She hopes it might empower communities, enabling them to take precautions before they get sick, and ultimately save lives. 

– Myles Gough

This article on biosensors was first published by Australia Unlimited on 19 January 2017. Read the original article here.

biophotonics

Biophotonics pioneer

Featured image above: biophotonics Professor Dayong Jin. Credit Vanessa Valenzuela Davie

Professor Dayong Jin envisions a future where portable diagnostic devices will be as ubiquitous as smartphones, where scientists can peer inside individual cells, and where diseases can be detected before they infect our bodies.

A pioneer in the emerging field of nanoscale biophotonics at the University of Technology Sydney (UTS), it’s a future Jin is working hard to create.

“The nanoscale is really the fundamental level on which biological molecules operate,” he says. “It’s the scale of the original disease.”

Jin engineers functional nanoparticles – invisible to the naked eye – which harness light to probe our cells, detect diseases and deliver drugs in perfectly measured doses.

Transforming the biomedical industry with biophotonics

Jin was recently named the Director of a new A$3.7 million Australian Research Council Industrial Transformation Hub. The hub’s objective is to develop portable diagnostic devices with vastly improved detection capabilities.

These easy-to-use devices, which incorporate nanomaterials and photonic technologies developed by Jin and his colleagues from UTS and the University of South Australia, can analyse incredibly small samples of substances including breath, saliva, urine and blood, to find markers of disease.

Jin says these point-of-care technologies will ease the burden on hospitals and align with the demands of consumers: real-time health monitoring, and faster treatment options.

“In the near future, prostate cancer patients who have gone into remission will have a handheld device at home to analyse their urine samples,” he says. “It will be able to tell them whether their cancer is recurring.”

The hub is also working with industry partners to develop an improved roadside breath-testing device for police forces to detect traces of illicit drugs.

Over its five-year lifespan, Jin expects the hub to generate a number of new portable diagnostic devices, which can be tailored to specific applications to detect everything from cancers to infectious diseases and environmental pollutants.

Super Dots diagnose diseases inside the body

Jin is also helping improve disease diagnosis from inside the body itself.

Cancers and infectious disease outbreaks all originate from a single cell, he says.

“The current challenge is that we don’t have a method to find this very rare cell from the earliest stage.”

Jin was part of an Australian research team that developed a technology known as Super Dots, which won a prestigious Eureka Prize in 2015. These nanoparticles can find a needle in a haystack, detecting individual diseased cells from a population of millions.

The particles are made from a nanocrystal material that can absorb invisible infrared light and emit higher energy, visible light, says Jin.

Once the nanoparticle has found the target cell inside the body, or a blood sample, it can be stimulated by researchers with a harmless, skin-penetrating infrared light.

The dot then emits a visible flash, which causes the diseased cell to light up.

“It’s like you have the diseased cell glowing in the darkness,” says Jin. “This allows you to achieve the ultimate detection sensitivity.”

Beyond medicine, Super Dots can be encoded with “secret signatures” and used for the anti-counterfeiting of passports, banknotes and drug labels, says Jin.

There are also applications for more efficient solar cells and 3D display screens.

Biophotonics pioneer featured video above: Superdots, WINNER 2015 Eureka Prize for Excellence in Interdisciplinary Scientific Research.Credit: Australian Museum.

Breaching the blood-brain barrier

Jin is hopeful that another class of his nanoparticles will serve as a versatile drug delivery vehicle, capable of breaching the protective blood-brain barrier.

Delivering drugs to individual neurons in the brain is a “holy grail problem” in neurological research, says Jin.

“There are many drugs already developed to treat Alzheimer’s and Parkinson’s quite effectively outside the body,” he says. “But the blood-brain barrier prevents more than 99 per cent of drugs from accessing the brain from the blood circulation system.”

Jin and his colleagues have created a library of 800 types of nanoscale drug carriers with specific shapes, sizes and surface functionality. Importantly, they have developed a process to replicate these carriers exactly, according to any design.

“We’ve solved the problem in terms of developing the material,” he says.

“If the tailored drug carrier can tell the blood-brain barrier that the carriers are the friend and not the enemy… we can open a gate into the brain.”

Super-resolution microscopy breakthrough

biophotonics
Super resolution image of the single cell nuclear membrane pores. Credit: Professor Dayong Jin.

Jin’s research has led to a recent breakthrough in the field of microscopy.

With colleagues at Georgia Institute of Technology in the US and Peking University in China, Jin has developed a simple but highly effective way to see individual cells in 3D – overcoming a major barrier. Instead of growing cells on transparent glass slides, the team grew their cells on specialised mirrors. As reflected light passed through the cell while being viewed under a super-resolution microscope, researchers could see new structures in exquisite detail.

“This simple technology is allowing us to see the details of cells that have never been seen before,” says Jin. “We can see the tiny little hole on the cell nucleus’ membrane – that hole is the entrance and exit for single molecules.

“When the cell wants to express a signal, or send a message outside the cell, this is the gateway – and we now have the tool to see what that looks like.”

By understanding how cells behave, communicate and how diseases arise inside them, researchers can develop more effective treatments.

Jin and Professor Peng Xi from Peking University hold a patent for their invention, and Jin says they are currently exploring opportunities to commercialise the technology with leading imaging companies such as Olympus and German firm Leica.

Multiculturalism trumps geography for Australia

It was love that brought Jin to Australia from his home in northeastern China, near the border with inner Mongolia. His future wife, Lisa Li, came to Sydney to study accounting in 2002, and he followed.

Jin ended up at Macquarie University in the laboratory of Dr Jim Piper, a renowned expert in lasers, optics and photonics. Under his guidance, Jin developed a system to detect trace amounts of pathogens in water.

Jin says the postgraduate scholarship in Australia was more comprehensive and generous than what was offered to his Chinese peers who chose to study in the US.

Jin says he and his family had planned on returning to China or finding a postdoctoral position in the US after his PhD, but ultimately decided to stay in Australia.

He says the decision has been good for his career: “Geographically, Australia looks like it’s isolated,” he says. “But we are actually well connected.

“The Australian research community is very multicultural, and these ‘soft connections’ have created a lot of opportunities for my research collaborations.”

Jin says multidisciplinary knowledge and collaboration is vital to realising the healthcare future he envisions – and going even further beyond.

In addition to his many breakthroughs in biophotonics, one of the prospects Jin is most excited about is that of truly personalised medicines.

At present, people with the same diseases are all treated with the same drugs, which might be totally ineffective for a proportion of the population, says Jin.

“But future medicines will have a tool to decode the unique molecular signature of a patient,” he says.

It means when two people have the same disease, they could be treated remarkably differently – with dramatically improved outcomes.

This is where we’re heading, he says.

– Myles Gough
This article on the biophotonics pioneer, Professor Dayong Jin, was first published by Australia Unlimited on 9 August 2016. Read the original article here.