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Research Projects and Laboratories

Before filling out your application, read each of the laboratory descriptions below. Several of the labs offer more than one project. If you are selected to work in a particular lab, you can discuss the projects with your mentor.
 
1. Optical coherence tomography (Faculty Mentor: Prof. Brett Bouma, WCP)
 
Goal: Develop new techniques for interferometric sensing and imaging via narrow diameter fibers, catheters and endoscopes for biomedical applications.
 
Project:  Optical coherence tomography is an imaging modality that provides high resolution, cross-sectional images of biological tissue structure and that is compatible with flexible, narrow diameter catheters and endoscopes. Projects focus on the development of new techniques for improving resolution, reducing speckle, enhancing depth range, and extending the capabilities of minimally invasive imaging probes. These projects involve electrical engineering, computer science, and mechanical engineering skills and expose students to a solid understanding of the physical principles underpinning modern OCT technology.
 
2. Coherent Raman scattering microscopy (Prof. Conor Evans, WCP)
 
Goal: Develop and apply microscopic optical imaging techniques for quantitative analysis of therapeutic response in skin
 
Project: Melanoma is a deadly disease, but the processes that lead to treatment resistance in melanoma are not well understood. We will develop new nonlinear and advanced microscopy technologies based on absorption and Raman contrast that enable deep imaging of biological processes within melanomas including drug update and cell death.
 
3. Photodynamic Therapy (Prof. Tayyaba Hasan, WCP)
 
Goal: To develop molecular mechanism- and optical imaging-based combination treatment regimens in which the first treatment primes/sensitizes cancer cells for the second treatment.
 
Project 1: Chemistry- Chemically engineer constructs and their physico-chemical characterization for optimal targeting of disease specific cellular and molecular markers. The engineered constructs include macromolecules (antibody, peptides, polymers), nanoparticles, and small molecule constructs.
 
Project 2: Imaging 3-dimensional tumors during photodynamic therapy. This project is divided in to two broad categories: (i) engineering molecular probes for multifocal imaging of complex biological samples, and (ii) development of imaging hardware, for example: video rate hyperspectral microscopic imaging.
 
Project 3: Infectious diseases- Tissue engineered 3D models, chemical constructs and optical technologies developed above are used for the development of enzyme-specific anti-microbial PDT. Target organisms in the infectious diseases are leishmaniasis, Mycobacterium tuberculosis and methicillin-resistant Staphylococcus aureus.
 

4. Optical sensors and imaging devices (Prof R. Rox Anderson, MD, WCP Director; Assistant Prof Walfre Franco, PhD)

Goal: to develop portable and/or wearable, optical sensors and imaging devices for monitoring physiologic data.

Project 1: Development of mobile phone-based imaging platform for evaluating the spatial and temporal features of cutaneous lesions. In this project, students will help to develop computer vision algorithms and optical methods for quantifying and analyzing variations in the optical environment of cutaneous tissues using a mobile phone camera platform. Additionally, the students will learn how to leverage optical hardware to probe tissues and improve image quality and resolution while minimizing motion and lighting artifacts. The hardware and software developed in this project will create simple-to-use low-cost technologies for diagnosis and evaluation of treatment response of common dermatologic lesions.

Project 2: Development of a wearable mobile optical sensor for tracking spectroscopic changes in tissue. LEDs and optical sensors can be integrated into wearable patches for longitudinal measurement of tissue optical properties. In this project, students will learn about electronic circuit design, spectroscopy, wearable devices, and will help to develop non-invasive probes for tracking changes in tissue, for example, sub-millimeter dynamics of cutaneous lesions or oxygenation states. These sensors may ultimately be deployed in wound care settings and, in collaboration with biologist, free-diving seals.

5. In vivo microscopy and cytometry (Prof. Charles Lin, WCP)
 
Goal: Develop optical techniques for tracking cells in live animal models of human disease. Specifically, we are interested in tracking immune cells, cancer cells, and somatic stem cells, as the trafficking of these cells from one location in the body to another is important in processes ranging from immune response, cancer metastasis, to regenerative medicine. We built custom instrumentation optimized for specific biomedical problems.
 
Project 1:  In vivo analysis of circulating blood cells. The ability to perform noninvasive blood analysis will be useful in situations where repeated blood sampling is problematic, such as in newborns and leukemia or HIV patients. The Lin lab has developed the technique of in vivo flow cytometry for real-time detection and quantification of circulating cells without needing to draw blood samples. Previously we have focused on fluorescence detection and demonstrated noninvasive cell count in animal models where the cells of interest are fluorescently labeled (Fan et al Nature Medicine 2010, Runnels et al J Biomed Optics 2011). For clinical translation of this technology, however, label-free detection will be critical. To achieve this goal, two complementary approaches are being pursued, one based on cellular autofluorescence and the other based on light scattering signals. Participating students can work on projects related to instrumentation or signal analysis directed at circulating cell count.
 
Project 2: The eye as a natural window for noninvasive imaging of central nervous system inflammation. The retina is an optically accessible part of the central nervous system (CNS) owing to the transparency of the eye. Under normal conditions the retinal parenchyma is separateded from the circulatory compartment by the blood-retina barrier (BRB). Similar to the barrier in the brain, the BRB can be breached in the condition of inflammation. Using scanning laser ophthalmoscopy together with mouse models of multiple sclerosis and brain injury, we demonstrate that the eye provides a natural window for noninvasive imaging of CNS inflammation. Students can participate in the development of a scanning laser ophthalmoscope with adaptive optics for imaging inflammation in human patients.
 
6. Optical microrheology of tissues and cells (Prof. Seemantini Nadkarni, WCP)
 
Goal: Develop novel optical tools for in situ use to obtain key insights on the micro-mechanical behavior of tissue and cells during disease progression.
 
Project 1: An optical blood coagulation sensor

The goal of this project is to develop a low-cost, multi-functional blood coagulation sensor that can measure a patient’s coagulation status within 5 minutes using a drop of blood. This device addresses the critical unmet need to identify and manage patients with an elevated risk of life-threatening bleeding or thrombosis, the major cause of in-hospital preventable death. In addition, this innovation will enable rapid coagulation testing in the doctor’s office or at home for over 15 million patients worldwide who routinely receive oral anticoagulants to prevent venous and arterial thrombosis, the world’s number one killer.

Project 2: Laser Speckle Microrheology to evaluate the mechanical hallmarks of tumor malignancy

There is growing recognition that the stiffness of the extracellular matrix (ECM) is a powerful regulator of cell response, and the differentiation, proliferation and malignant transformation of tumor cells can be modulated by tuning ECM mechanical properties. These insights indicate that cancer is mediated by a dialogue between ECM mechanical cues and oncogenic signaling, and therefore knowledge of ECM mechanics is important for advancing current understanding of tumorigenesis and for developing new therapeutic paradigms. In this project we will develop hybrid imaging approaches that combine confocal microscopy and microrheology techniques to investigate the structural and mechanical hallmarks of tumor malignancy.

7. Photo-crosslinking of natural polymer scaffolds (Prof. Robert Redmond)
 
Goal: Develop improved methods for synthesis of photo-crosslinked materials for tissue engineering and medical use.
 
Project: Photo-crosslinked natural polymers as tissue engineering scaffolds. Light can be used in conjunction with a photo-initiator to crosslink polymeric materials and the extent of crosslinking can determine the biomechanical properties of the material and its suitability for encapsulating cells. REU students will learn the optical approaches to crosslinking, the sources involved and optical and other methods for testing the extent of crosslinking in the material. Vehicles include hydrogels, electro-spun collagen and silk films and mats and multilayered membranes. Fluorescence microscopy will be used to determine cell viability and matrix structure in these materials following crosslinking. 
 
8. Novel miniature endoscopic microscopes (Prof. Gary Tearney, WCP)
 
Goal: Develop novel optical tools for in situ use to obtain key insights on the micro-mechanical behavior of tissue and cells during disease progression.
 
Goal: Develop non-invasive, high-resolution optical imaging methods for disease diagnosis.
 
Project 1: Comprehensive confocal endomicroscopy.

Diagnosis of esophageal diseases is often hampered by sampling errors associated with the standard endoscopic biopsy. The Tearney lab has developed an innovative optical microscopy technology, spectrally encoded confocal microscopy (SECM) that obtains confocal images 2-3 orders of magnitude faster than conventional raster scanning devices. From several clinical studies imaging human patients in vivo, the SECM endoscopic capsule devices have been shown to successfully visualize cellular features from the entire esophagus. There are several research opportunities for REU students, including 1) designing and testing of a motor-scanning SECM capsule prototype, 2) development of ultra miniature imaging probes for other applications inside the body, and 3) creation of automated tissue classification algorithms.

Project 2:  Smart Tethered Capsule Endomicroscopy.

The current standard diagnostic tool for upper gastrointestinal tract disorders, endoscopic biopsy, has many limitations as it is invasive, costly, and suffers tissue sampling error. In order to overcome these limitations of endoscopy, the Tearney lab has developed a new imaging concept termed tethered capsule endomicroscopy (TCE), which involves swallowing a tethered capsule that acquires three-dimensional microscopic images of the entire gastrointestinal tract as it traverses the luminal organ via peristalsis or is pulled up towards the mouth using the tether. Applications span all of upper endoscopy including cancer and inflammatory diseases of the esophagus, stomach, and small intestine.  TCE research topics for REU students include: 1) design and validation of prototype capsules with integrated sensing capabilities; 2) the development of multimodality capsules that implement structural and chemical/molecular imaging, and 3) programming machine learning algorithms for real-time TCE diagnosis of a variety of gastrointestinal tract conditions.

9. Optical coherence microscopy (Prof. Benjamin Vakoc, WCP)
 
Goal: Develop coherent optical imaging platforms that can be deployed endoscopically to diagnosis and guide the treatment of disease at earlier stages. Our methodology for achieving these aims combines a core focus on optical technologies with cross-disciplinary collaboration and broad-based engineering.
 
Project 1: Development of mode-locked comb sources for high-speed optical coherence tomography.
 
The Vakoc lab has recently developed a new high-speed and long imaging optical coherence tomography (OCT) architecture that opens new opportunities in diagnostic imaging. The architecture relies on mode-locked comb sources that are distinct from traditional wavelength-swept laser sources for OCT. Here, students will participate on building new laser configurations, quantifying their optical performance, and numerically modeling the underlying optical physics of these sources. Students will be mentored in these projects by senior group members and will gain experience in lasers and optics including test and measurement skills.
 
Project 2: Analysis of polarization-sensitive optical coherence tomography datasets.

Polarization-sensitive optical coherence tomography (PS-OCT) provides multi-dimensional signals that describe the interaction of light polarization with a tissue sample. These signals can be used to provide unique insight into underlying tissue organization and health. However, the analysis of these signals is complex and features are often subtle. In this project, students will work with existing PS-OCT datasets to evaluate and optimize processing and quantification algorithms. Students will be mentored by senior group members but will work independently to gain experience applying mathematical frameworks to biomedical imaging datasets.

10. Micro optics and biocompatible devices (Prof. S. H. Andy Yun, WCP)
 
Goal: Develop novel bio-lasers and bio-devices.
 
Project 1: Implantable hydrogel optical waveguides.

The Yun lab makes pioneering efforts in the field of biomaterial-based photonic devices, such as light-guiding hydrogels and biocompatible waveguides, to create implanted optical devices for health monitoring and therapies. Students working on this topic will design, fabricate, and characterize novel polymer-based or hydrogel-based waveguides, and they will acquire knowledge on waveguide optics, biomaterials, nanofabrication, and their applications.

Project 2: Wearable optical sensors.

Light emitting diodes and optical sensors can be integrated into flexible substrates for wearable patches for longitudinal measurement of tissue optical properties for tracking spectroscopic changes in tissue.  In the Franco lab in collaboration with Yun lab, students will learn about electronic circuit design, spectroscopy and wearable devices, and help to develop non-invasive probes for tracking changes in tissue, sub-millimeter dynamics of cutaneous lesions or oxygenation states. These sensors may ultimately be deployed in wound care settings and, in collaboration with biologists, free-diving seals.

Project 3: Biological cell lasers.

The Yun lab is pioneering the field of bio-lasers. The group has demonstrated fluorescent-protein lasers, cell-dye lasers, all-biomaterial laser, and intracellular micro-lasers. These works, which are supported by NSF grants, have received considerable public exposure through numerous news media and awards. These new lasers have potential for imaging, biological sensing, and cell tracking.  Students will learn how to generate and detect laser light from micro-cavities, how cells uptake micro lasers, how the intracellular environment affects the output characteristics of the lasers, and the novel applications of cell lasers.

Project 4: Brillouin optical microscopy for cell biomechanics.

The Yun lab has previously developed high-resolution Brillouin light scattering microscopy for studying cell biomechanics. By measuring the optical frequency shift of the scattered light, Brillouin measurements probe the local spontaneous pressure waves in the intracellular environments, from which one can determine high frequency longitudinal modulus that is related to the modulus of individual cytoskeletal components, network crosslinking, compressibility of the local microenvironment, and solid-liquid volume fraction. In this project, REU students have the opportunity to participate in new instrumentation and use a state-of-the-art setup to measure the stiffness of the extracellular and intracellular matrices and study their interplay in stem cell differentiation, in synergy with an ongoing NSF-funded research.