The Biomedical Engineering REU is designed to provide independent research experience for undergraduate students, broaden participant knowledge of opportunities in academia, industry and national laboratories, and introduce participants to interdisciplinary research in biomedical devices.
The goal of every medical practitioner is to improve quality of life for patients. Biomedical engineering and devices are instrumental in achieving this. The primary focus in each summer research project is biomedical devices designed to enhance medical care through science and engineering, with emphasis in two areas: (1) devices for diagnostics and sensing and (2) devices for therapeutics and intervention.
All projects are designed to be completed during the 10 week program and are a part of a faculty mentor's current research. This allows the student to be involved in many aspects of research, including design, analysis, simulation, and implementation of a biomedical device.
Students are also extensively involved in lab activities, such as weekly lab meetings. Research results are presented during lab meetings throughout the summer and at the end-of-summer in the Summer Research Symposium poster session. Lab members, especially graduate students and postdoctoral associates, are active with summer program research.
Competitive stipend: $6,000
Suite-style room and meal plan
Travel expenses to and from Lincoln
Campus parking and/or bus pass
Full access to the Campus Recreation Center and campus library system
Measuring Transient Cerebral Blood Flow Changes from Sensory Stimuli Using Transcranial Doppler
Ultrasound is a safe, noninvasive method of measuring blood flow in the body, and transcranial Doppler (TCD) is a special ultrasound mode that measures blood flow in cerebral arteries deep in the brain. TCD may be used as an inexpensive, portable method to measure brain response since neural activity is correlated with blood flow in the cerebrum. For example, a visual stimulus (such as a strobe light) can evoke a change in blood flow to the visual cortex. This can be seen by a relative decrease in the flow within the middle cerebral artery compared to the posterior cerebral artery. For clinical reporting, blood flow measurements are typically reduced to a pulsatile or resistive index. However, this index is typically based on long-term (i.e., tens of seconds) averages of data, and averaging removes the valuable real-time aspect of ultrasound.
This project will assess the use of a new data index based on systems theory (relaxation time). The REU student working with Dr. Bashford will immediately be taught to scan subjects; by the first week’s end, s/he will be able to measure blood flow in a fellow student. By week four, the student will have participated in experiments scanning 10 human subjects designed to test the index described above. The following three weeks will be devoted to learning and performing data analysis. In the final third of the summer, the student will be encouraged to develop (and present to Dr. Bashford’s lab) his/her own ideas about what the next steps would be if (s)he were in charge. The student also will prepare a poster for the UNL Research Symposium, and if results warrant, draft a paper for peer-reviewed publication. In parallel, throughout the summer s/he will learn to draft hypotheses based on known physiological time effects to stimuli and anatomy; and perform a literature review in a specific area (e.g., visual or aural) of his/her own interest.
Nanoparticle-mediated sensitization of pediatric brain tumors to radiotherapy
Pediatric brain tumors contribute disproportionally to mortality in children because of the lack of available treatment options. Radiotherapy is one of the few effective adjuvant therapies available for these tumors after neurosurgical resection, but survival is frequently accompanied by radiation-induced lifelong developmental and learning disorders. As such, there is a significant need to reduce the amount of radiation required to achieve a curative effect. The goal of this project is to use brain tumor targeted nanoparticles to selectively sensitize pediatric brain cancer cells to radiotherapy.
The student working with Dr. Kievit will be introduced to nanoparticle drug delivery vehicles as well as the mechanism of action of radiotherapy, namely DNA damage-induced cell death and the various strategies cancer cells utilize to form resistance. Simultaneously, the student will be trained on pediatric brain cancer cell culture and methods to assess cell viability. Once this is complete, the student should be able to formulate a hypothesis on how to achieve the project goal as well as methods to test this hypothesis. Advanced students will also learn how to synthesize the nanoparticles that will be used in the summer experiments. During the middle of the summer, the student will use their developed skills to test their hypothesis by generating and interpreting in vitro results. During the final third of the summer the student will reformulate their hypothesis based on their preliminary results and use their methods to re-test this hypothesis (search and re-search!). During this project, the student is expected to gain an understanding of the limitations of pediatric brain cancer treatment and how nanoparticle engineering strategies can be used to overcome these limitations. The student will get hands-on experience in human cancer cell culture, nanoparticle synthesis strategies, methods of treating cancer cells, and methods for assessment of treatment efficacy. The student will also get the experience of processing, analyzing, and interpreting experimental data, as well as data presentation in written and oral form.
Molecular Mechanosensors of Flow-induced Stem Cell Migration
Migrating mesenchymal stem cells (MSCs) contribute to homeostasis and modulate the repair of damaged tissues in vivo . MSC migration-dependent regenerative medicine strategies such as cell therapies have, however, suffered from low efficiency in cell homing to the target tissue. While conventional soluble factor-driven static chemotaxis experiments have revealed some aspects of MSC migration and homing , there is a huge knowledge barrier with regard to how mechanical environments such as fluid flow-induced shear stress affect MSC migration . Considering MSCs in vivo are exposed during migration to fluid flows in the blood vessel and interstitial space, this study investigates how physiologically relevant fluid shear conditions will affect MSC migration behavior.
The REU student will learn by week two how to apply fluid flow stimulation to the cells using a well-defined macro-flow chamber and how to analyze cell migration with the imaging tools developed in the lab. In weeks three through six, s(he) will be able to test the effects of physiological fluid shear stresses (5, 10, 20 dyne/cm2) on MSC migration in the absence or presence of a silenced molecular mechanosensor, e.g., small hairpin RNA (shRNA) of focal adhesion kinase (FAK). In the final third of the summer, the student will be encouraged to develop his/her own idea about which molecular mechanosensor would be tested as a potential effector to mediate flow-induced MSC migration. The student will prepare a poster presentation for the UNL Summer Research Symposium, and potentially draft a manuscript for a conference abstract or journal paper. Throughout the summer, in parallel, the student will be taught how to formulate hypotheses based on observed fluid shear-induced MSC migration behavior, and perform relevant literature reviews.
Developing the next generation of wearable computing
Wearables have emerged as an increasingly promising interactive platform, imbuing the human body with always available computational capabilities. This unlocks a wide range of applications, including discreet information access, health monitoring, fitness, and fashion. However, most commercially available wearables are primarily composed of traditionally rigid materials (e.g., metals and hard plastics), limiting their placement to locations of low movement or flexibility (e.g., wrist). To enable access to additional locations, the next generation of wearables will be constructed out of soft, “skin-like” materials that closely match the mechanical properties of biological tissue. This REU project will work towards developing new soft, “skin-like” materials and holistic fabrication approaches that push the practical boundary of on-skin electronics that are not only functional but aesthetically pleasing.
Dr. Markvicka's lab is developing the next generation of wearable computing that is structurally conformal, comfortable to wear, and soft, elastic, and aesthetically appealing. We envision a future where electronics can be temporarily attached to the body (like bandages or party masks), but in functional and aesthetically pleasing ways. Towards this vision, the REU student will create a new electronic material, where functional stiffness gradients can be easily programmed to limit the stress concentrations around rigid integrated circuits (IC) that are embedded within a soft, “skin-like” material (by week 3). The REU student will experimentally characterize and optimize the functional stiffness gradient to limit the strain applied to the IC (by week 5). The new electronic material we be used to create a wearable biomonitoring electronic bandage for monitoring heart rate (by week 7). It is expected the REU student will learn about material selection; fabrication techniques including soft lithography and UV laser micromachining; electronics prototyping and circuit design; and mechanical, electrical, and electromechanical characterization techniques and will be exposed to methods for biosignal monitoring.
Robotic Technology for Next-Generation Minimally Invasive Surgery
Robotic tools are becoming a standard fixture in medicine, and particularly in surgery, where they can help enhance dexterity and visualization in minimally invasive approaches. Inserted, in-vivo robots (like miniature surgeon arms inside the abdomen) can have particularly high functionality. However, the small electric motors that typically drive these surgical robots are problematic: they take up too much space for too little force and speed capability, and electrical connections multiply the possible failure modes and reduce reliability.
Dr. Nelson’s lab is developing strategies for actuator integration and modularity to increase functionality and reliability of these surgical robots while dramatically lowering cost. The specific research purpose of this project is to investigate the efficacy of different actuator and linkage layouts to maximize robot functionality and reliability. The REU student will perform hands-on testing of prototype robot components (beginning in week 1) and collect data (beginning in week 2) on their performance. As (s)he gains familiarity with the project, the participant will progress to computer-aided design (by week 4) and simulation and prototype fabrication (by week 6) of his/her own original designs and/or modifications to existing designs. It is expected that along the way, (s)he will learn and apply principles of robot kinematics and dynamics, biomaterials selection, and engineering design methodology, along with somewhat lighter exposure to anatomy/physiology and computer science.
High Throughput Screening of Clinical Compounds that Prime Nonviral Gene Delivery in Human Mesenchymal Stem Cells
Human mesenchymal stem cells (hMSCs) are a multipotent cell type found in numerous tissues in the human body, such as bone marrow, fat, and muscle. Due to hMSCs multipotency and ease of obtaining, they have become one of the most widely researched stem cell types in fields such as tissue engineering and regenerative medicine, and applications like targeted delivery of drugs/secretion of therapeutic proteins, and cancer therapy. An area of high interest within these areas is genetic modification of hMSCs, which could be used to differentiate hMSCs, or to produce therapeutic proteins and signaling molecules. However, potential clinical success of genetically modified hMSCs has been hindered by low efficiency of gene transfer to hMSCs via nonviral vectors. While previous research has focused on modifying the delivery vector to increase transfection of hMSCs, the Pannier Lab is focused on identifying endogenous cellular factors, altered through chemical priming of clinically approved drugs that are important for successful nonviral gene delivery to hMSCs.
The student working with Dr. Pannier will be taught the basics of cell culture and nonviral gene delivery within the first three weeks, while also learning to analyze current literature and think critically about experimental procedures to formulate pertinent research questions. For the following three to four weeks, the student will assist Dr. Pannier in screening a library of compounds for priming nonviral gene delivery in multiple donors of hMSCs from various tissues, while also proposing and testing protocols for validation of hits (compounds that significantly increase transgene expression compared to a vehicle control). The remaining third of the summer will consist of data analyses to group and sort hits, while also analyzing compounds that significantly effect nonviral gene delivery to hMSCs, to begin to tease apart the mechanisms that are causing these effects.
The REU participant is expected to gain experience in critical thinking and literature searching pertaining to research, while also learning basic cell culture techniques and assays through extensive hands on learning. The student will learn the basics of nonviral gene delivery to hMSCs, and how chemical priming can alter nonvriral gene delivery outcomes, and will also learn to process and analyze data to produce meaningful results. Finally, the Pannier Lab hopes that the student will gain a deeper understanding of what takes place in a research lab, while also gaining a deeper appreciation for science, engineering, and research.
Fabrication of Microscale Hydrogel Beads Using Cross-flow-based Droplet Generation
Microscale hydrogel spheres have been widely used for biomedical research, such as cell encapsulation or three-dimensional cell culture. This project aims to fabricate such hydrogel beads using our cross-flow-based drop generator. In this effort, the water-based pre-polymer solution of a hydrogel will be injected through a syringe needle into mineral oil that rotates in rigid body motion. Then, monodisperse droplets of the solution will be generated at the needle tip by the motion of the oil, and the polymerization of the droplets will be controlled by either ultraviolet light or chemical cross-linkers.
The REU student will immediately participate in the project based on the following plan: (s)he will be trained for the cross-flow drop generation and general hydrogel fabrication (weeks 1-2); participate in fabricating hydrogel beads using the cross-flow-based drop generation (weeks 3-5); learn image processing and conduct data analysis to characterize fabricated hydrogel beads (weeks 6-7); and then develop her/his own ideas to improve the project, prepare a poster presentation for the Summer Research Symposium, and draft an abstract for a conference (weeks 8-10). In parallel, the student will join the lab journal club throughout the summer to learn literature review and scientific writing, and be mentored to conduct a literature survey for her/his own project-related question and develop a hypothesis on the process of hydrogel bead fabrication.
Disappearable Cyber Physical System Sensors and Actuators
The goal of this REU research proposal is to enable the next generation of wearable sensors and actuators: those that disappear within the natural orifices of the human body. Specifically, we will use the gastrointestinal (GI) tract as a location for a long-term biosensing and control application. Doing so will enable invisible, unobtrusive, long-term physiological monitoring to address the problem of infrequent, clinic-based measurements. The GI tract is an ideal location for miniature biosensing systems due to its large volume and surface area, proximity to vital organs and systems, and because it is a natural pathway into and out of the body. In pursuit of this goal, the research objectives are to solve the problem of long-term persistence of sensors and actuators within the GI tract which will require in vitro and in vivo testing and trials of new attachment designs, methods, and systems.
The REU student will move the research along these trials. Prior to arriving at UNL, the REU student will perform a literature review and complete online training and certifications to work with animals in a clinical veterinary research setting. This will enable the student to begin immediately upon his or her arrival with the necessary hands-on training of handling animals that will be used in experiments. The first three weeks will be spent in this way while assisting a graduate student with his or her animal-related work, thus receiving additional hands-on training. In parallel, the REU student will develop a hypothesis and design an experiment that he or she believes will push the boundaries of the research. Dr. Terry will directly oversee this effort and help the REU student devise a project plan that is reasonable in scope to be carried out during the last month of the program. During the remaining month, roles will be reversed and the graduate student mentor will assist with the REU student’s research project and will continue to provide mentorship while performing the experiments, analyzing the data, and formulating conclusions. The REU student will present the results of this work during a poster session at the end of the program.
Biomaterials and therapeutics to prevent low back pain
Low back pain is one source of orthopedic pain recognized as a widespread clinical problem resulting from degeneration and innervation of the intervertebral disc. Prevention of nerve growth into the intervertebral disc and reduction of painful stimuli has the potential to prevent disc-associated low back pain independent of disc degeneration. Our lab develops natural biomaterial scaffolds to prevent undesired nerve growth and reduce nerve stimulation. This project will work on developing and characterizing these natural material scaffolds and drug delivery devices to treat low back pain. Over the course of the first two weeks, the REU student will learn basic lab techniques such as how to isolate natural scaffolds, how to make decellularization chemicals, and how to decellularize tissue. During weeks three and four, the student will learn cell culture techniques and assays for analysis. For the remainder of the summer, the student will culture various cell types including nucleus pulposus cells, macrophages, and/or stem cells in the decellularized tissue matrices to determine the effects of the matrix on cell phenotype and protein production.