Opthalmologist on a chip: Fully integrated microfluidic tear osmolality and protein biomarker quantification for dry eye stratification

Kelly Karns

Ph.D. Candidate, Professor Amy Herr’s Lab, UC Berkeley

Abstract

Human tear film fluid offers tremendous potential as a non-invasive diagnostic fluid. However, the use of tear fluid in diagnostic medicine is limited owing to non-standardized collection methodologies and low volume availability. I will present a first-reported microfluidic tear fluid biomarker assay which will serve as a foundation for both rapid biomarker validation and point-of-care ocular diagnostics. Our microfluidic approach demonstrates multiplexed quantitation of both tear fluid osmolality and lactoferrin (Lf) protein concentration in microliter quantities of human tear fluid from healthy and Sjögren’s syndrome (SS) patients. Lf is a tear-specific biomarker for SS, a serious systemic autoimmune disease currently diagnosed through rudimentary tear volume, ocular surface chemistry measurements and an invasive lip biopsy. Meanwhile, tear osmolality is a putative marker of overall dry eye disease severity and can provide a quantitative assessment for patient-specific treatment. Taken in sum, this work details important steps toward (1) expanding the set of proteins quantified by electrophoretic immunoassays to encompass a wider range of isoelectric points than has been reported, (2) creating a first-in-kind translatable assay with clinical relevance to SS and dry eye diagnostics, and (3) expanding the analytical toolkit available for rapid biochemical measurements in tears, as is relevant to the advancement of basic research and clinical medicine.

Speaker Biography

Kelly Karns is a Ph.D. Candidate in Professor Amy Herr’s lab. She received a B.S. in Bioengineering and Mechanical Engineering from Yale in 2007 and an MS in Bioscience Enterprise in 2008 before joining the Joint Graduate Group in Bioengineering at UC Berkeley/UCSF. She is currently working to miniaturize traditional laboratory biochemical analysis techniques for applications requiring the use of small sample volumes.

About the Point-of-Care Diagnostics Idea Lab

The Point-of-Care Diagnostics (POCDx) Idea Lab was created as a forum for graduate students who are working in the areas of medical diagnostics and global health to discuss topics relevant to their research.  Students working in the areas of engineering, science, policy, and healthcare are encouraged to attend.  The bi-weekly meetings will be informal and will usually include one or two short presentations by graduate students, faculty, or other outside speakers affiliated with POCDx.

This video was originally recorded on October 25th, 2011 in 621 Stanley Hall, UC Berkeley

The Role of Diagnostics in Infectious Disease Control: A Look at TB in the San Francisco Area

Dr. Masae Kawamura

Director, Tuberculosis Control Program, San Francisco Department of Public Health

Abstract

Dr. Kawamura will present the challenges associated with tuberculosis control in the San Francisco area, as well as some of their ongoing and investigational initiatives to combat the spread of the disease through innovative diagnostic tools.

Speaker Biography

Masae Kawamura, MD has been a tuberculosis (TB) clinician for more than 20 years, serving as Director of San Francisco’s TB Control Program since 1996. Under her leadership, San Francisco became the first jurisdiction in the U.S. to implement Interferon gamma release assay (IGRA) blood testing for TB. Currently, TB Control is also participating in studies preliminary to acceptance of the new sputum-sample based GeneXpert TB test, from Cepheid.

A Co-Principal Investigator for Curry National TB Center, a CDC–affiliated Regional Training and Medical Consultation Center, Dr. Kawamura has served on the faculty since its inception in 1994. She also served on the CDC Advisory Council for the Elimination of TB (ACET) for eight years, the last three as chair, and continues to serve on subcommittees of the group. Dr. Kawamura is an assistant clinical professor at the University of California–San Francisco (UCSF) and has coauthored numerous TB publications. She is currently president of the International Union Against Tuberculosis and Lung Disease (IUATLD), North American Region.

About the Point-of-Care Diagnostics Idea Lab

The Point-of-Care Diagnostics (POCDx) Idea Lab was created as a forum for graduate students who are working in the areas of medical diagnostics and global health to discuss topics relevant to their research.  Students working in the areas of engineering, science, policy, and healthcare are encouraged to attend.  The bi-weekly meetings will be informal and will usually include one or two short presentations by graduate students, faculty, or other outside speakers affiliated with POCDx.

This video was originally recorded on May 24th, 2011 in 621 Stanley Hall, UC Berkeley

Microchip-based point-of-care (POC) technologies to measure HIV-1 viral load information

Utkan Demerci, Ph.D.

Assistant Professor of Medicine and Health Sciences and Technology, Harvard University Medical School and MIT

Abstract

Currently, more than 30 million people are living with HIV-1 worldwide. Based on 2010 WHO guidelines (treatment initiation at CD4 cell count <350 cells/mm3), only approximately 36% AIDS patients are receiving anti-retroviral therapy (ART) in low- and middle-income countries. The low coverage of ART program is mainly due to the lack of cost-effective diagnostics to monitor CD4 cell count and viral load in AIDS patients in resource-limited settings, despite the fact that first-line ARV drugs become cheaper or even free. To overcome this challenge, we developed microchip-based point-of-care (POC) technologies to count CD4+ T lymphocytes and provide viral load information. On a microchip coated with immobilized antibodies, CD4 T lymphocytes were captured from whole blood and subsequently counted using a lensless image technology. This portable, battery operated, lensless, microchip platform showed significant correlation in CD4 T-cell counts compared with the gold standard, i.e., FACS counts both at BWH in Boston (r: 0.94, p<0.01), and MUHAS in Tanzania (r: 0.49, p<0.01). The device rapidly produced CD4 T-cell counts within 10 minutes using an automated cell counting program. Using a similar microchip platform, HIV was also be captured by immobilized antibody and detected by quantum dot based staining. In conclusion, this microchip platform technology can potentially deliver inexpensive, rapid and simple testing to monitor antiretroviral treatment in resource-limited settings.

Speaker Biography

Utkan Demirci, Ph.D., is an Assistant Professor of Medicine and Health Sciences and Technology at Harvard University Medical School and MIT (Massachusetts Institute of Technology). Dr. Demirci received his B.S. degree in Electrical Engineering in 1999 as a James B. Angell Scholar (Summa Cum Laude) from University of Michigan, Ann Arbor. He received his M.S. degree in 2001 in Electrical Engineering, M.S. degree in Management Science and Engineering in 2005 and Ph.D. in Electrical Engineering in 2005 all from Stanford University. In 2008, Dr Demirci was given Department of Medicine, Harvard Medical School-Young Investigator Award; The Outstanding Young Persons of the World, Junior Chamber International (JCI). In 2006, he was selected to TR-35 as one of the world’s top 35 young innovators under the age of 35 by the MIT Technology Review. Dr. Demirci has published more than 50 peer reviewed journal publications, more than 50 conference proceedings and 10 book chapters. His research interests involve applications of microelectromechanical systems (MEMS) and acoustics in medicine, especially: microfluidics for inexpensive CD4 counts for HIV in resource-limited-settings for global health problems; cell-by-cell 3D tissue printing; high-throughput blood biopreservation; oocyte vitrification. Dr. Demirci leads a group of 30 researchers focusing on nano and Sciences and Technology, Center for Bioengineering, Brigham and Women’s Hospital, Harvard Medical School.

About the Point-of-Care Diagnostics Idea Lab

The Point-of-Care Diagnostics (POCDx) Idea Lab was created as a forum for graduate students who are working in the areas of medical diagnostics and global health to discuss topics relevant to their research.  Students working in the areas of engineering, science, policy, and healthcare are encouraged to attend.  The bi-weekly meetings will be informal and will usually include one or two short presentations by graduate students, faculty, or other outside speakers affiliated with POCDx.

This video was originally recorded on April 25th, 2011 in 621 Stanley Hall, UC Berkeley