Ben Hansson Research CBRG

Research

The goal of the LAMPE (Laser-Assisted Medical Physics and Engineering) Lab is to develop optical methods based on Raman Spectroscopy (RS) and Non-Linear Optical (NLO) imaging that enable rapid, non-invasive, cost-effective and highly accurate disease diagnostics and treatment. Using near-infrared laser light to excite vibrations of molecular chemical bonds (in RS), and nonlinear interactions with molecules (in NLO imaging), these methods provide highly detailed chemical, structural and functional information about cells and tissues in real time, without the use of external contrast agents (label-free). In combination with machine learning techniques, this enables us to effectively identify, quantify and differentiate between the response of cells and tissue exposed to different types of external stress such as disease and ionizing radiation. The ultimate goal of this research is to translate these optical techniques to the clinical and diagnostic lab setting.

Raman spectroscopy of cells, solid and liquid tissue.

Current biochemical methods for the assessment of cellular and tissue response to stress inflicted by factors such as cancer, are severely limited for single cell analysis, require complex sample preparation and assess only a single stress biomarker. In contrast, Raman spectroscopy along with multivariate analysis techniques enables rapid molecular fingerprinting of single cells and tissue to assess multiple biomarkers in a single measurement with minimal sample preparation. Our team has developed a  Raman micro-spectroscopy setup that is completely customizable in the spirit of "Lego-Optics". 

Raman setup and spectra

Using these techniques, we have successfully identified for example, ovarian cancer cells from healthy cells, chemo-sensitive vs chemo-resistant ovarian cancer cells, and demonstrated novel through-the-surface detection of the composition of cartilage (e.g. for osteoarthritis) up to a depth of ~0.5 mm. These results support the potential for developing Raman spectroscopy-based methods for early disease diagnostics and treatment monitoring. 

Coherent Raman, multimodal Non-Linear Optical imaging

NLO imaging includes multiple modalities such as Coherent Anti-Stokes Raman Scattering (CARS), Stimulated Raman Scattering (SRS), Second Harmonic Generation (SHG) and Two-Photon Excitation Fluorescence (TPEF) imaging. NLO imaging provides rapid label-free, chemical imaging with high spatial resolution and inherent 3D sectioning capability. The open frame modular architecture of our multimodal NLO imaging platform employs a dual output laser with ~100 femtosecond pulses that are temporally broadened to a few picoseconds for CARS and SRS. The laser-scanning microscope is re-configurable and uses novel detection based on silicon photomultipliers that have important advantages over conventional photomultiplier tubes.

NLO-Harry-images

Using this setup we recently reported for the first time, novel TPEF imaging-based metrics for quantifying the metabolic response of immune cells treated with bacterial and viral load. We are proud to be a core member of the multi-disciplinary Tissue Engineering and Applied Materials (TEAM) Hub at Carleton. For a CIHR-funded project in collaboration with Prof. Fred Leblond and Dr. Dominique Trudel at the Centre de Recherche du Centre hospitalier de l'Université de Montréal (CRCHUM) in Montreal, we are currently developing CARS and SRS imaging-based techniques to identify an aggressive variant of prostate cancer. We will employ image segmentation and classification approaches based on state-of-the-art machine learning and deep learning algorithms. 

Ionizing Radiation dosimetry based on Raman spectroscopy

Accurate and high precision determination of the dose of ionizing radiation are crucial in the current goals for ionizing radiation therapy (RT) and radiation protection (RP). Current techniques in bio-dosimetry (for RP) are technically complex, labour-intensive and time-consuming while experimental micron-scale dosimetry (for RT) remains a challenge to date. We have demonstrated a sensitive Raman micro-spectroscopy-based technique to detect the effects of low (< 1 Gy) doses of ionizing radiation in human lens epithelial cells; these results are significant for RT and RP. We also reported a Raman spectroscopy-based high-throughput technique involving blood with > 90% discrimination accuracy of control vs oxidized blood in collaboration with Dr. Vinita Chauhan's team at Health Canada. The Raman data pre-processing techniques for blood Raman spectra developed in the LAMPE Lab are suitable for wider applications including blood-based bio-dosimetry and liquid biopsy. We are currently enhancing our recently published methods for Raman micro-spectroscopy of radiochromic films to enable high spatial resolution dosimetry. 

Development of compact Raman and NLOM systems

Sangeeta's experience in the photonics industry (JDS Uniphase) and her work as a Research Associate at University of Ottawa in Prof. Hanan Anis's lab, led to two photonics solutions that are significant for future clinical and industrial translation: i) the first portable miniaturized multimodal CARS  microscope with a ~10,000x smaller footprint compared to a commercial microscope, 

and ii) a novel cost-effective (50% cheaper) excitation source for CARS imaging using a single femtosecond laser. At Carleton, we have built cost-effective (25% of the cost of commercial systems) platforms for Raman micro-spectroscopy and multimodal coherent Raman, NLO imaging. Our ultimate goal is to develop compact solutions for wider adoption in clinical and diagnostic lab settings. 

 

 

 

Collaborators

Dr. Frederic Leblond and Dr. Dominique Trudel, Centre de recherche du Centre hospitalier de l'Université de Montréal
University of Ottawa
Dr. Barbara Vanderhyden, the Corinne Boyer Chair in Ovarian Cancer Research, University of Ottawa.
University of Ottawa
Dr. Hanan Anis and Dr. Robert Boyd, University of Ottawa.
University of Toronto
Dr. Brian Wilson, Department of Medical Biophysics, University of Toronto and the Princess Margaret Cancer Center, Toronto.
Health Canada
Dr. Vinita Chauhan, Dr. Sami Qutob and Dr. Ruth Wilkins in the Consumer and Clinical Radiation Protection.
The Ottawa Hospital
Dr. Balazs Nyiri, Medical Physicist at the Ottawa Hospital.