Michelle Khine - US grants

DESCRIPTION (provided by applicant): The main objective of this proposal is to develop a high-throughput intracellular drug screening platform. Fluxion proposes a rapid, safe, and efficient method to access proteins in the intact cell, by traversing the cell membrane, to facilitate functional screening of intracellular proteins as potential drug targets. This proposal focuses on developing a microfabricated single cell electroporation array which introduces otherwise impermeable drug compounds into the cellular array to dynamically screen for interactions between the compounds and the proteins. The completed array platform has functions including automatic single cell trapping and electroporation, rapid compound insertion, and multiplexed real-time optical and electrical monitoring. The specific aims of this project are to: I. Determine efficient electroporation conditions to open pores on the cell membrane and enable their resealing. II. Ensure optimal dosing of the drug compounds. III. Improve device design for multiplexing assays and for high-throughput.

This Nanotechnology Undergraduate Education (NUE) in Engineering program entitled, Bridging Education and Research: Practical Applications of Nanotechnology, at the University of California-Merced, under the direction of Dr. Jennifer Lu, will, using existing collaborations, initiate a range of activities that include developing an upper-level, team-oriented, self designed laboratory course on nanoscale device fabrication, organizing a two-day nanofabrication workshop for local community colleges, and facilitating internship opportunities in nanotechnology.

The proposal for this award was received in response to the Nanotechnology Undergraduate Education (NUE) in Engineering Program Solicitation (NSF 07-554), and is being funded by the Directorate for Engineering (ENG), Division of Engineering Education and Centers (EEC) and the Division of Civil, Mechanical and Manufacturing Innovation (CMMI).

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Immobilize streptavidin labeled Qdots on the gold wrinkles, petals and glass plates modified with biotin-BSA. Obtain fluorescence images and intensity time trace of single particle on each substrate by one-photon and two-photon confocal microscopies. Comparing the results to demonstrate metal nano-wrinkles and [unreadable]petals can enhance fluorescence emission. Culture cells with EGFP expression on the wrinkles and petals. Using wrinkles and petals as substrates for metal enhanced fluorescence cellar imaging.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our project in the LFD involves using the spectrophotometer to analyze the light transmission through polyolefin. We are concerned that during one of the steps in the production of our chips, shrinking our polymer through heating, that it will become too opaque to be used in the expected applications. We would like to test different protocols to determine if one reduces the opacity.

DESCRIPTION (Provided by the applicant) Abstract: My goal is to enable the early and rapid detection of infectious diseases by developing extremely low cost, high specificity and ultra-high sensitivity plastic chips. Saliva can thus be rapidly analyzed for important protein markers with low-powered, inexpensive off the shelf components. Early, rapid, and quantitative detection would enable pathogens to be identified at the patients'locale, triggering of surveillance alerts, administration of proper treatment, and containment of the infectious disease. With adequate tools, one could identify different pathogen strains, patterns of drug resistance, and sources of outbreaks. Detection, diagnosis, treatment, and surveillance of infectious diseases in the developing world is critical to universal public health. Early detection enables prompt and more effective treatments, contains the spread of diseases, and reduces the cost to public resources on ineffective responses. The goal of this proposal is to develop and deploy my chips for the detection of the infectious and deadly rotavirus disease. While traditional optical detection is expensive with power-hungry analytical instrumentations inappropriate for point of care (POC) in developing countries, I seek to provide a low-cost portable system (with laser diode and photo-detector for <$100) with disposable robust plastic chips (with integrated metallic nanostructures for surface enhanced sensing) that can be manufactured for less than $0.20 a piece would enable true POC diagnostics for developing countries. Because the detection is based on antibody capture, this device could be used to diagnose almost any known infectious disease. These modular microfluidic-based components would allow multiplex testing as well, enabling the detection of infections as well as co-infections by examining a panel of protein markers in saliva. My unique integrated nanostructures within these chips enhance the signal by several thousand folds, enabling ultra-high sensitivity immunoassays. Public Health Relevance: Early detection of infectious diseases enables prompt and more effective treatments, contains the spread of diseases, reduces the cost of public resources on ineffective responses, and alerts us of emerging diseases. A versatile and field-rugged platform technology that is widely deployable yet sensitive and robust enough to be efficacious in detecting specific infections and co-infections at their very onset is needed.

Abstract

1212234, Khine

Intellectual Merits: Micro- and nanotechnologies have emerged to become one of the most ?game changing? fields in science over the past few decades. In particular the ability to control and manipulate matter at small length scales has already led to major advances in a range of different areas such as microelectronics, energy, biomedicine and environment. Given the increasing amount of interest in this area the ?Micro- and Nanotechnology in Medicine Conference? (MNMC) aims to bring together leading experts in the area of micro- and nanotechnology to present the latest work on the use of various types of technologies for addressing a range of different challenges that are of importance for biomedicine and education of engineers at the interface of engineering, medicine, and biological sciences. This conference will be held in Hawaii, on Dec 2-6, 2012. The conference organizers have partnered with IEEE-EMBS (IEEE- Engineering in Medicine and Biology Society), one of the leading societies at the interface between engineering, biology and medicine, to present a program that is highly rich in both intellectual merit as well as educational opportunities. In particular the conference brings together students from various academic institutions with world leading experts in a small and intimate setting that will enable ample opportunities to network and learn. The conference will focus on a number of unique areas that are highly inter-related yet not fully put together in a similar program. These areas include fundamental science of micro- and nanofluidics and small matter to applications in engineering the environment of cells using various ?small-scale? technologies, developing devices to detect and analyze molecules for biosensing and global health applications. Another unique aspect of the conference is the involvement of people from companies. The proposed conference will generate a range of opportunities for students and young investigators to learn about the process of developing and commercializing a technology from industry speakers.

Broader Impacts:
The potential impact of this proposed MNMC is far-reaching. Because this conference combines fundamentals of micro and nano science and engineering with their applications in medicine, it will catalyze conversations between otherwise disparate fields. Various biomedical grand challenges facing our society and the world can be addressed in part or in whole by interfacing biology and medicine with nanotechnology. By drawing leaders from each of these fields together to discuss ways of addressing important medical issues with the most cutting edge technology in an intimate venue, it will enable progress at the interface of science, engineering, and medicine. To maximize the broader impact of such a promising conference, several approaches are proposed to raise awareness, with the larger scientific community as well as engage participation by under-represented minorities by hosting:

1. Workshops for students to engage more intimately with thought leaders. Students can get to know leaders in the field through workshops to help guide and further their careers. Having access to mentors is a critical component for a successful education, and therefore providing a forum to engage mentor and student interactions would help facilitate this.

2. Women in Science, Engineering, and Medicine Panel Luncheon. With still so few women in engineering and science, a panel luncheon in which women can learn from established role models as well as open a dialogue on how to best attract and engage women in these burgeoning fields is needed.

3. Best poster awards for undergraduates and for graduate students. poster competitions will be held to encourage the highest quality research and presentation at the undergraduate as well as at the graduate level.

4. Travel grants for US students. These grants will enable students who otherwise cannot afford to come to participate in this conference. The grants will be distributed based on merit (quality of paper submission) with consideration for inclusion of under-represented minorities and women.

This Integrative Graduate Education and Research Traineeship (IGERT) award initiates a novel model for interdisciplinary graduate training in biophotonics across the biomedical sciences, physical sciences, and engineering. Biophotonics technologies provide powerful capabilities to probe and manipulate biological components and processes. Their utilization in the life sciences and medicine represents an estimated annual economic impact of $50 billion. This program aims to produce the next generation of biophotonics leaders to make transformative advances in the development and application of new tools for biological and medical discovery and maintain global U.S. leadership in biotechnology, pharmaceutical and medical device industries.
Intellectual Merit: This IGERT award creates a hands-on training program that integrates physics, chemistry, engineering, and life-science principles across spatial and temporal scales. The interaction of, and collaboration between, biomedical scientists, physical scientists and engineers throughout the graduate traineeship will drive advances in biophotonics technologies, computational methods, and molecular probes to solve important problems in bio-molecular, cellular, tissue, and whole organismal systems.
Broader Impacts: The BEST IGERT project will promote dissemination of an innovative education framework aimed towards a diverse cadre of scientists and engineers. Moreover, IGERT faculty and trainees will engage vigorously in a spectrum of outreach, dissemination, recruitment, retention, and career development activities that leverages the commitment of multiple units within UC-Irvine, industry in Southern California, and a nationwide network of faculty contacts, including those at minority serving institutions, to inform the public and broaden participation by students from underrepresented groups.

IGERT is an NSF-wide program intended to meet the challenges of educating U.S. Ph.D. scientists and engineers with the interdisciplinary background, deep knowledge in a chosen discipline, and the technical, professional, and personal skills needed for the career demands of the future. The program is intended to establish new models for graduate education and training in a fertile environment for collaborative research that transcends traditional disciplinary boundaries, and to engage students in understanding the processes by which research is translated to innovations for societal benefit.

1445881
Khine, Michelle
University of California-Irvine
Title: UC Bioengineering Symposium: Educational Awards to be held in Irvine, CA on June 18th-20th, 2014.

Layperson description
The broad goal of this UC Systemwide Bioengineering Symposium is to bring leading experts in biology, medicine, materials, and engineering with industry leaders to translate innovative engineering technologies and methodologies to effectively sense, diagnose and treat medical disorders and diseases.
This symposium will draw new participation and foster interdisciplinary research and education, particularly students and junior faculty, including underrepresented groups. There will be numerous networking opportunities to stimulate scientific and technical discussion with senior investigators and industry leaders. We will also have a focus on engaging women at the undergraduate level to stay in the engineering field. We will have special emphasis on undergraduate senior design awards. The broader impacts and goals are to develop a robust pipeline for discovery and development of medical therapies, diagnostics and research technologies to cure diseases and injury.

Technical description
Biomedical grand challenges facing our society can be addressed in part or in whole by interfacing stem cell -, synthetic -, or systems biology with biomedical engineering tools (including microfluidics, nanomaterials and nanotechnology, cellular and molecular machines, bioinspired materials and structures) and engineering principles (such as biophotonics, transport phenomenon, drug delivery). By drawing leaders from each of these fields (from both industry and academia) together to discuss ways to address pressing medical issues with the most cutting edge technology in a highly interactive venue, we will enable progress at the interface of science, engineering, and medicine. Requested funding for this proposal will enable support for registration fees for the best student participants, provide funding for student awards (oral and poster presentations and innovation competitions) and provide funding for junior faculty awards (innovation competition).

With a decline in Americans pursuing advanced education in STEM fields (more than 67% of engineers receiving Ph.Ds in the U.S. are not U.S. citizens and only 18% of engineers are female, it became apparent that priming the pipeline with diverse, qualified, and prepared students is mission critical. Understanding, actively engaging, and retaining a diverse population of inquisitive students prepared with critical thinking skills is paramount. Recent studies have shown that active learning, which engages children in activities and involves interactions with peers, as opposed to passive listening, emphasizes higher-order thinking and results in significantly better comprehension and performance. To address this national problem, this team has developed the "A Hundred Tiny Hands" that focuses on teaching modern science concepts in a playful and cooperative way, through a combination of physical Inventor?s Toolboxes and an online social media platform.

A Hundred Tiny Hands proposes 3 avenues for adoption: direct to consumers; working with after school / outreach and children's organizations (including Girl Scouts and Big Brothers Big Sisters); and adoption from private, charter schools and eventually public school districts. The typical user for the (initial) Inventor's Toolboxes is a child (especially girls) between the ages of 6-10. The buyers for the 3 different scenarios, however, are very different. For the direct to consumer approach, the buyers would be the parents, typically highly educated, tech oriented professionals with disposable income who understands the importance of STEM literacy. In order to reach a broader demographic and children who otherwise would not have access to such toys, the team has forged relationships with various children?s programs, outreach/low income programs, and after school/ summer camps. Finally, the team is working with key decision makers of school districts and charter schools to gain adoption into the STEM curriculum.

By leveraging the unique physics of flow on non-wetting superhydrophobic surfaces, this research seeks to overcome the persistent bottlenecks associated with manipulating fluids at extremely small volumes (microfluidics). While microfluidics holds much promise for early and deployable disease diagnostics, practical challenges associated with such precision manipulations have heretofore hindered its widespread dissemination. Microfluidics on superhydrophobic surfaces can solve many disease diagnostic problems by enabling: loss-less sample manipulations, novel hydrodynamic properties, extremely fast and controlled flows, and enhanced mixing. The knowledge and insight generated through this research will significantly improve and propel the field of microfluidics forward by elucidating the fundamental mechanisms of enhanced flow through engineered surface effects. It will also enable practical implementation and deployment of these mechanisms for real-world impact. Broader impacts of the work include the potential for mass manufacture superhydrophobic surfaces in commodity plastics and integration of them into microfluidic devices already in use. Additional impacts include K-12 science and engineering outreach programs, one entitled "A Hundred Tiny Hands" developed for children (ages 5 and up) where they can design and make their own superhydrophobic building blocks as part of our 'Inventor's Toolboxes' while learning modern science and engineering concepts with our accompanying comic books.

This research involves the creation and implementation of superhydrophobic surfaces in commodity plastics on the large scale with standard roll to roll manufacturing, which allows the optimization of such substrates and enables the ability to inexpensively integrate them into standard microfluidics devices. This research systematically designs and optimizes both superhydrophobic surfaces and microfluidic designs to best leverage surface enhancements for key microfluidic-enabled diagnostic functionalities. Goals of the research are to create mass manufacturable configurable superhydrophobic surfaces tailored for specific microfluidic applications so they can be integrated into commercial microfluidic devices by probing the physics at the micro- and nano-scale. Other goals include pushing the current limits of our understanding of the physics of microfluidics, with an outcome that is physically tangible: i.e., mass manufactured diagnostic devices with significantly improved performance due to integrated superhydrophobic surfaces.

Project Summary The Virtual Reality Unmet Clinical Needs course offered at the junior level will engage undergraduate engineering students using online and immersive active learning techniques to develop intuition, teamwork skills, and unmet clinical needs evaluation prior to their senior capstone course, the BioENGINE program. This course will be offered through online websites and virtual reality applications to allow large institutions and those without access to medical centers to be able to perform clinical immersion and unmet clinical needs finding for all undergraduate biomedical engineering students. Through immersive technologies such as virtual reality, simulations, and online lectures using manikins and staged real-life simulations, we will provide a large class size of students the opportunity to understand how medical devices are used in the real world, and identify novel potential commercializable solutions that they will develop during their senior capstone course. To accomplish this, students will work in multidisciplinary teams to develop a proposed innovative medical solution identified through the immersive clinical environments exploration and filmed clinician interviews. By having all students in the curriculum the ability to perform unmet clinical needs identification and evaluation through virtual immersion, we will provide an inclusive online active learning program to all students in our program as well as those at other institutions. Through this strategy, all biomedical engineering students will gain more practice, depth, and experience in listening, learning, and designing a solution to an unmet clinical need, we hope to gain a more effective method of teaching biomedical engineers how to solve problems in a real world situation, and how to communicate in a team more effectively.