(6al) Developing Tools for Emerging Liquid Biopsy Applications | AIChE

(6al) Developing Tools for Emerging Liquid Biopsy Applications

Authors 

Contreras-Naranjo, J. C. - Presenter, Texas A&M University
Research Interests:

My Ph.D. work at Texas A&M University focused on developing methods to optically probe surface interactions of microspheres and biomimetic systems such as polymer vesicles. The combination of theoretical, modeling, computational, and experimental approaches produced a significant breakthrough using an interference-based technique to enable fast and nanometer-scale reconstruction of the geometry of curved microscopic objects near surfaces. During my post-docs at the University of California, Los Angeles, and Texas A&M, I have grown as a researcher in the development of next-generation imaging and sensing platforms based on lens-free computational microscopy, label-free quantitative imaging tools, smartphones, and microfluidics, applied to emerging liquid biopsy analysis in my most recent work.

To pursue research as a faculty, I am uniquely equipped to tackle interdisciplinary problems at the interface between engineering, optics, biology, and medicine. In particular, personalized medicine enabled by liquid biopsy of bodily fluids for early disease diagnosis, treatment monitoring, and patient prognosis, faces important technological challenges depending on the targeted biomarker (e.g., bulk fluid, cells, exosomes, and cell-free nucleic acids). For instance, antibody-based approaches for the detection of circulating tumor cells (CTCs), cancer cells in circulation that could be responsible for metastasis at distant sites, typically involve complex workflows that potentially miss metastatic cells not targeted by the antibodies used. Alternatively, label-free interference-based quantitative imaging can be performed at the single-cell level for identification of highly metastatic cells using label-free fingerprints such as adhesion and filopodia dynamics. This approach overcomes limitations of conventional analysis methods while offering great potential for label-free phenotyping of cells in a broader context. Similarly, liquid biopsy is not limited to cancer, with advancements in exosome-based analysis enabling minimally invasive access to a wide range of pathologies, including diabetes, inflammation, acute kidney injury, concussion, cardiovascular disease, alcoholic liver disease, and central nervous system diseases.

The development of point-of-care (POC) tools for analysis of bodily fluids such as blood is thus fundamental in the routine establishment of liquid biopsy in the medical field. Microfluidic platforms that process small sample volumes (microliters) in portable easy-to-operate and low-cost set-ups are called to play a central role in such applications. As an example, blood viscosity analysis at the POC can be enabled by self-driven capillary flow in microchannels that are large enough to be monitored and recorded using a smartphone. Such capillary filling dynamics span an important range of shear rates that can be modulated to accurately probe the rheological behavior of complex fluids. This will enable probing blood viscosity as a potential biomarker in diabetes and cardiovascular diseases, which has been hindered by the complexity associated with conventional methods to measure blood rheology.

Therefore, building on my expertise and skills, I aim to integrate novel and powerful imaging and sensing tools and approaches into portable and low-cost liquid biopsy analysis platforms to facilitate personalized medicine. This will be achieved through fundamental research, a combination of theoretical, modeling, computational, and experimental approaches, and emphasis on the development of platforms for high-throughput analysis of bio-colloidal systems. Recent advances in lens-free computational microscopy and smartphone-based microscopy and sensing aided with artificial intelligence techniques represent extremely valuable tools for POC applications and are expected to play a key role in my future research.

Teaching Interests:

Teaching in chemical engineering offers a unique opportunity for motivating students, especially at the undergraduate level, by providing a variety of real-life scenarios where new concepts can be applied, even to understand natural phenomena around us. This is fundamental in my teaching philosophy, where inquisitive questions (e.g., how do tall trees transport water from their roots to the top?) are presented to the students before a new topic (e.g., capillary phenomena) is introduced. In addition, interactive in-classroom experiences that help measure/visualize/illustrate content being learned are integral part of my approach. For this purpose, smartphones can be readily exploited as powerful scientific/educational tools, capturing images, videos, and incorporating virtual and augmented reality technologies. For instance, I have worked with Honors students in the Fluid Operations course to develop a portable smartphone-enabled capillary-based viscometer. It is also important to recognize that knowledge is not complete, and concepts learned in classrooms could lead to more questions and technological developments. Thus, I finish course materials by making students wonder, highlighting recent progress and challenges ahead in the ever-evolving chemical engineering field.

I feel confident in my ability to teach most of the traditional subjects in the chemical engineering curriculum at the undergraduate level, and my preferences are Transport Phenomena and Process Dynamics and Control. I am also interested in developing an elective course on colloidal science and quantitative imaging methods that can be taken by both graduate and undergraduate students.