Purple for malaria, green for HIV

Purple for malaria, green for HIV

Nearly instantaneous testing for a long list of diseases is not as far off as you might think
January 9, 2014

When Warren Chan arrived in Toronto in 2003 to found the Integrated Nanotechnology & Biomedical Sciences Laboratory (INBS) at the University of Toronto, the city was reeling after an outbreak of SARS, a viral respiratory illness that killed 44 residents and resulted in the quarantine of 25,000 others. “I came in when that whole craziness was happening,” recalls Chan. “You start putting two and two together.”

Two and two in Chan’s mind meant a connection between infectious disease and the groundbreaking research he’d already done to show that nanocrystals — semiconductor particles known as quantum dots — could have biological applications. “You ask yourself what’s needed in terms of medical diagnostics,” says the youthful Chan, sitting on a wooden bench in his bright, compact corner office. “And what’s needed are simple, quick tests.”

Easier said than done. The typical diagnostic test in use today, known as ELISA (enzyme-linked immunosorbent assay), requires a significant sample size of blood, sophisticated (read “pricey”) equipment, expert technicians and time — sometimes weeks — to complete. In developing countries, meanwhile, there is an ever-present need for portable diagnostic tools that are either less expensive, simpler or more accurate than those in use today.

Chan and his team at INBS may be on the verge of changing all that. Their answer: a hand-held diagnostic tool that can tell a person within 20 minutes whether he or she tests positive for HIV, hepatitis B or C, malaria or syphilis — or any number of other illnesses or genetic conditions. The key to making this possible is molecular bar codes created using tiny plastic beads composed of nanoparticles of cadmium and selenium that are 1,000 to 100,000 times smaller than the width of a strand of hair. These beads are embedded in a chip. Different types and sizes of nanobeads bind to different target molecules corresponding to particular diseases to reveal a certain colour. The colours glow brightly and don’t fade, giving them two chief advantages over the organic dyes used in other optical diagnostic technologies: photostability and visibility.

You simply prick your finger and let a few drops of blood fall into a tube or onto a slip of paper containing the nanobead chip, then wait. A colour signal emerges that can be viewed through the camera of a cellphone. In a test for the deadly type of malaria, for example, you might start with green beads in a vial with a purple compound. If the pathogen for this malaria is present, its DNA would bind the green bead to the purple compound, and the overall bead colour would change from green to a combination of green and purple. Chan calls this a “sandwich” model, in which the pathogen’s DNA is the peanut butter stuck between the nanobead and the indicator molecule. If the disease is not present, only the green beads would be visible. By combining several different colours of nanobeads, it is possible to test for several conditions simultaneously. “Once we design the bar codes, we can recognize each one of them by their unique colour patterns,” says Chan. “That’s the beauty of this system.”

The technology’s potential implications are vast, especially when you consider a public health crisis such as SARS and the significance of an extremely quick and reliable diagnosis. Chan himself foresees a time when the average person could be walking around with his or her own diagnostic kit. He likens the pace of change in nanodiagnostics to how quickly YouTube has permeated our culture. “This is where medical diagnostics is moving,” he says. “This stuff is not so far away as you think.”

Quantum dots were 25 years in development by the time Chan hit the scene in 1998 while working on his PhD in analytical chemistry at Indiana University. Back then, quantum dots were seen mainly as tools for the computer and electronics industries. But Chan’s advisor, Shuming Nie, now a faculty chair in biomedical engineering at Georgia Tech/Emory University in Atlanta, brought Chan into his lab as a graduate student to make nanoparticles soluble in water — the first step toward making them useful to biology. “Warren Chan is a very creative guy,” says Nie. “He thinks out of the box. I actually assigned this project first to another student, and he could not do it. He told me it was impossible. Warren was able to do it in two months. Now he’s the international leader in this field. In terms of diagnostic application of quantum dots, Warren is leading the way.”

Chan credits Nie with instilling in him a pervading ethic: to always keep an eye on how his research might be useful in the real world. He continues to think this way as Cytodiagnostics, the Bdefaultington-based nanotechnology company he co-founded with Scott Kordyban and for which he remains a chief advisor, works on how to turn the diagnostic prototype into an easy-to-cart, low-cost, self-contained kit. His team must also improve the longevity of the bar codes: The crystals begin to break down after a few months. “We’re working on usability,” says Chan, who’s in discussion with researchers in Uganda regarding a potential collaboration. “The next phase is to talk to the people on the ground and work to make it fit their needs. What you need for malaria diagnosis might be very different from what’s needed for diagnosing HIV.”

The protoype itself looks innocuous. The black plastic device, made with a 3-D printer, fits in the palm of your hand and contains a low-power laser and an amplifying lens. “You slide your cellphone right in,” says Chan. It has a gap where the bar-code chip sits directly opposite the eye of the phone’s camera. It cost $500 to make, but Chan says all but $80 of that went to the 3-D printing fee, high because only one was made.

Chan’s Toronto-based quantum-dot research was conducted with the help of close to $2 million worth of sophisticated equipment funded by the Canada Foundation for Innovation, including a system that allows for chemical testing in an air-free environment and a machine that measures the spectral properties of quantum dots. “This is standard equipment,” says Chan. “We use it probably 24 times a day.”

We’re at least a few years away from the time when travellers routinely stuff self-diagnosis gizmos into their backpacks or public health clinics have instant diagnosis at hand during flu season. But the process to commercialize the nanobead bar codes is under way, and several labs in North America are following Chan’s lead: applying nanotechnology to medical diagnosis. “What you want to do is put the information out there so that other people can use it,” says Chan. “It’s an exciting time for the field of nanotechnology. The next 10 years will really be the translation push.”