Integrating Nanotechnology with Microfluidics to Diagnose and Monitor Disease Progression at the Molecular, Cellular and Tumor Level

Panning for Gold: Are Nanomaterials the Future of Cancer Treatment?

Professor Michael Mason received BS degrees in Chemistry and Physics from University of Puget Sound in 1994 and 1995, respectively. He received his PhD degree in Physical Chemistry from the University of California, Santa Barbara in 2001. He then worked as a research fellow in the Department of Applied Physics at Yale University for three years on the development of single molecule imaging techniques for the non-destructive characterization of photolithographic structures, semiconductor materials, and sensing in complex and biological systems. 

Michael joined the faculty of the University of Maine in 2004 as an Assistant Professor of Chemical and Biological Engineering and adjunct faculty member of The Jackson Laboratories, and was appointed to Associate Professor in 2009. He has advised over 100 PhD, Masters, undergraduate and high school students in research, and has taught both undergraduate and graduate courses in Chemical and Biological Engineering. Professor Mason has published over 50 refereed journal articles, conference proceedings and book chapters. 

His current research is in nanomaterials, biophysics, nanomedicine, including cancer diagnostics, and instrument development.  He has been actively involved in science education and outreach to area schools in Maine over the past 10 years.

In a cross-disciplinary collaboration between researchers at the University of Maine and the Jackson Laboratory this project proposes to develop the enabling technologies required to monitor, over time, the biochemical changes that occur at the single cell level during the entire progression from healthy cell to cancer cell to tumor. This project will integrate emerging nanomaterials with microfluidic technologies, making it possible to observe time dependent biochemical changes within individual cells that are currently obscured by time and population averaging. This novel approach has the potential to generate previously unattainable information and may hold the key to developing new cancer-type specific diagnostic, therapeutic and monitoring strategies in both the laboratory and clinical setting. The disease progression from Myelodysplastic Syndrome (MDS) to acute myeloid leukemia (AML) will serve as the model system in this study as it is emblematic of many cancer types, showing broad variability between patients and throughout the progression to the acute state.

Current understanding suggests that carcinogenesis is the result of some critical number of normally occurring and constantly fluctuating, genetic errors that result from mutation, improper transcription or damage, and statistically accumulate over time. Existing methods, however, almost exclusively make use of time-insensitive biochemical approaches that average over large populations of cells. As a result, our ability to correlate cell function and biochemistry (including disease markers) with disease state, or progression, is severely limited. In a cross-disciplinary collaboration between researchers at the University of Maine and the Jackson Laboratory this project proposes to develop and implement the enabling nanotechnologies required to monitor, over time, the biochemical changes that occur at the single cell, and tissue mass, level during the progression from healthy cell to cancer cell to tumor. The specific aims of this effort are to:

  1. Construct and implement a microfluidic tissue incubator for use specifically in confocal Raman micro-spectroscopy of live cultures.
  2. Modify the surface of existing 'Nanostars' for improved uptake into cells for use as Raman signal enhancers and in vivo CT tissue mass contrast agents.
  3. Determine the spectroscopic markers of individual cells in the healthy – MDS – AML progression, in vitro.
  4. Use the Nanostar technology, spectroscopic markers and CT data to locate and biochemically stage tumors in an in vivo mouse model.

This proposal addresses a primary challenge in cancer research: Can we develop new tools that will help us elucidate disease progression at the molecular, cellular and tumor level, including reversible and stochastic processes? This project represents a significant departure from more traditional approaches to cancer research, and has the potential to dramatically advance our understanding of the disease progression at the molecular level. The new tools produced through this project (aims 1 and 2) will make it possible to dramatically increase our understanding of cancer and how it progresses, and could open the doorway to new preventative measures as well as diagnostic and therapeutic strategies. Specifically, new disease and disease state biochemical markers will be identified. Aims 3 and 4, will demonstrate the power of these new enabling technologies, potentially, revolutionizing our understanding of disease progression in bone marrow diseases (i.e. myelodysplastic syndrome - MDS) including the progression to acute myeloid leukemia (AML). Combined these disease states present with 5 year survival rates of around 50% and eventual survival rates of less than 25%, with around 13,000 new cases reported each year in the United States. Recent reports from The National Cancer Institute show that incidence rates for leukemia (all types) in Maine are at or above average and the death rate in Maine exceeds that of the nation

Beyond bench top research, this project also seeks to produce new tools for use in the clinical diagnosis, staging, and monitoring of cancer. In particular, the proposed nanotechnology will make it possible to visualize tumor growth non-invasively (CT) AND stage the cells in the tumor mass non-invasively, or minimally invasively, in minutes using Raman micro-spectroscopy and the elucidated disease markers. Unlike current contrast agents, this new nanotechnology will remain IN the tumor mass over time, obviating the need for repeated application of potentially nephrotoxic contrast agents, while simultaneously improving overall contrast and the ability to visualize tumor margins. Combined, this could dramatically reduce patient discomfort, decrease diagnostic time and reduce both cost and liability for cancer patients here in Maine and across the Nation.

Organization: 

University of Maine

Researcher: 

Michael Mason, Ph.D

Grant Amount Given: 

$168,309

Year Issued: 

2014

Period: 

Annual

Grant Category: 

Research

Types of Cancer: 

All
Cellular
Molecular

Grant Duration: 

2 Year Accelerator Grant

Other Maine Cancer Foundation Grants to this Organization: