Molecular medicine has a critically important role in the future of health care. For example, effective tools for the detection of molecular markers of health and disease are essential for personalized medicine. Moreover, equitable and inclusive health care across Canada and the world requires that the tools for detection are not limited to specialized laboratories in wealthy urban centres. To this end, we are developing platforms for the detection of biomarkers that combine advanced luminescent materials with prototype devices based on portable and mass-produced consumer electronics (e.g. smartphones). This research will be a basis for next-generation diagnostic tools.

Example publications:

• ACS Meas. Sci. (2022) in press.
• Anal. Chem. 91 (2019) 10955-10960
• Anal. Chem. 91 (2019) 11963-11971
• Anal. Bioanal. Chem. 408 (2016) 2913-2925 [Paper in Forefront]
• Analyst 140 (2015) 4037-4045 [Cover Feature]
• Anal. Chem. 86 (2014) 3195-3202
• Anal. Chem. 85 (2013) 8817-8825

Förster resonance energy transfer (FRET) is a powerful method for probing molecular interactions in real-time and with mix-and-measure simplicity. We invented concentric FRET (cFRET), which is a design strategy that uses a FRET network to enable a single nanoparticle vector to detect multiple analytes (e.g. biomarkers) in parallel. We are currently developing cFRET probes for cellular sensing applications, and exploring other novel designs of FRET networks for sensing. This research toward will provide new tools for elucidating complexing biochemistry and new platforms for diagnostics.

Example publications:

• Meth. Appl. Fluoresc. 7 (2019) 042001
• J. Phys. Chem. C 121 (2017) 13345–13356 [Cover Feature]
• J. Am. Chem. Soc. 139 (2017) 363-372
• Analyst 141 (2016) 3636- 3647 [Cover Feature]
• Anal. Chem. 87 (2015) 8078-8083
• Anal. Chem. 86 (2014) 11181-11188
• ACS Nano 6 (2012) 11044-11058

States of health and disease are molecularly complex, but simplicity is important for broadly accessible diagnostics. We are designing probes that can molecularly compute the detection or absence of multiple biomarkers into a single luminescent output through Boolean logic-like operations (e.g. AND, OR, NOT, NAND, NOR). Such probes have potential applications in rapid screening of disease (e.g. healthy or sick status), avoiding false positive and false negative results, and autonomously analyzing complex molecular expression patterns characteristic of disease.

Example publications:

• ACS Sensors 2 (2017) 1205-1214

To support our research toward next-generation molecular diagnostic devices and cellular probes, we are developing various types of luminescent nanoparticles. Areas of interest include improved chemistries for stabilization, functionalization, and immobilization of semiconductor quantum dots and semiconducting polymer dots, novel luminescent polymer nanoparticles (in collaboration with the Hudson Group), colloidal supra-nanoparticle assemblies, and colloidal super-nanoparticle assemblies.

Example publications:

• ACS Appl. Mater. Inter. 12 (2020) 33530-33540
• ACS Appl. Mater. Inter. 12 (2020) 53462-43474
• ACS Appl. Mater. Inter. 12 (2020) 6525-6535
• ACS Appl. Biomater. 3 (2020) 432-440
• Bioconjugate Chem. 31 (2020) 861-874
• Anal. Chem. 91 (2019) 11963-11971
• ACS Appl. Nano Mater. 2 (2019) 898-909

Nanoparticle surface chemistry provides opportunities to influence the activity of biological molecules. Our work in this area focuses on understanding how surface chemistry enhances, inhibits, and otherwise affects enzymes acting on substrates conjugated to a nanoparticle. We then leverage these effects to develop molecular diagnostics with optimized sensitivity and selectivity, and enhanced informing power.

Example publications:

• Langmuir 35 (2019) 7067-7091 [Cover Feature]
• Bioconjugate Chem. 29 (2018) 3738-3792
• ACS Appl. Mater. Inter. 9 (2017) 30359-30372
• ACS Appl. Mater. Inter. 7 (2015) 2535-2454

Nanoparticles are challenging materials: surface chemistry is fundamental to many of their properties but is difficult to characterize at the nanoscale; almost all nanoparticle preparations have heterogeneity in size, shape, and bioconjugation; and defects and impurities sometimes have significant effects. We are developing new methods that help address these characterization challenges.

Example publications:

• Analyst 143 (2018) 1104-1116

Fluorescence methods for the detection of single molecules and particles are very powerful—anomalous but important behaviour that is normally hidden in the ensemble average can be revealed, biomarkers can be detected with the ultimate sensitivity, and bimolecular or biological processes can be studied in fine detail. We are building and using systems for single molecule/particle imaging and measurements. This will work will accelerate our other research and open up new avenues of discovery.

Example publications:

• ACS Appl. Mater. Inter. 12 (2020) 33530-33540

The development of "smart" and other value-added probes for bioanalysis and imaging, it is necessary to understand photophysical properties and processes. To support our applied research, we do fundamental research to better understand energy transfer, charge transfer, quenching mechanisms, and other photophysics associated with luminescent materials. Our primary tools are various steady-state and time-resolved absorption and emission spectroscopies, both in our laboratory and via LASIR.

Example publications:

• J. Phys. Chem. C. 124 (2020) 17387-17400
• J. Phys. Chem. C 120 (2016) 17817-17828
• J. Phys. Chem. C. 119 (2015) 26183-26195
• ACS Photonics 2 (2015) 639-652 [Cover Feature]

The special properties of many nanoparticles are useless without effective functionalization. Nanoparticle surface chemistries and bioconjugate chemistries that minimize non-specific interactions and optimize specific binding and colloidal stability are essential for the development of molecular diagnostics and cellular probes. We are developing simple and effective methods for bioconjugation. This work will help support the reproducibility and scale-up required for downstream commercialization of nanoparticles for diagnostic technologies.

Example publications:

• ACS Appl. Mater. Inter. 12 (2020) 33530-33540
• ACS Appl. Biomater. 3 (2020) 432-440
• Bioconjugate Chem. 31 (2020) 861-874
• Anal. Chem. 91 (2019) 11963-11971

We aim to be toolmakers. We have ongoing collaborations and invite further collaborations with biological and health researchers who have scientific challenges that are potentially addressable with our materials, infrastructure, devices, and expertise.

Example publications:

• Bioconjugate Chem. 30 (2019) 525-530
• Bioconjugate Chem. 29 (2018) 136-148
• Biochim. Biophys. Acta - Proteins and Proteomics 1865 (2017) 1490-1499

We have expertise and supporting infrastructure for assay, probe, and sensor development, as well as for fluorescence spectroscopy, fluorescence imaging, and energy transfer studies. We have ongoing collaborations and invite further collaborations with researchers who have interesting materials, whether for potential applications in bioanalysis and imaging or for fundamental characterization.

Example publications:

• Chem. Commun. 56 (2020) 5556-5559
• Chem. Commun. 55 (2019) 5495-5498
• J. Phys. Chem. C 121 (2017) 28566-28575