At the Case Biomanufacturing and Microfabrication Lab, we strive to improve patients’ quality of life by innovating micro-, nano-engineered systems and technologies for clinical care. Active research topics include: microfluidic platforms to monitor sickle cell disease patients’ health, micro-electrophoretic screening of hemoglobin disorders, and management of joint and prosthesis health in military personnel and veterans via microanalyses on synovial fluid.
Biophysics, biofluids, cell mechanics: Monitoring and management of sickle cell disease
Healthy red blood cells are soft and are not sticky so that they can slip easily through even the narrowest of blood vessels in the body. Increased stiffness and stickiness of red blood cells can impair blood circulation and this does occur in many diseases and conditions, including anemias, sepsis, malaria, lupus, heavy metal poisoning, blood transfusion complications, diabetes, cancer, kidney and cardiovascular diseases, obesity, and some neurological disorders. Medicine does not have a complete understanding of the mechanical changes of red blood cells in these conditions.
Sickle Cell Disease (SCD) is the first recognized molecular disease, identified more than sixty years ago, and is caused by a mutation of the beta globin gene in hemoglobin. Replacement of a hydrophilic amino acid with a hydrophobic amino acid in the 6th position of the β-globin chain leads to polymerization of intracellular HbS and to the formation of stiff hemoglobin polymer structures within the cell. This mutation afflicts millions of people worldwide and is associated with considerable morbidity and mortality. Red Blood Cell (RBC) deformability, adhesion, hemolysis, and alterations in flow are root pathophysiologic underpinnings of SCD. We develop microfluidic systems that allow simultaneous interrogation of RBC biophysical properties in physiological flow conditions at a single cell level.
Summary
Understanding mechanical properties and biophysical interactions of blood cells have significant implications for monitoring and managing microvascular diseases and blood disorders.
Clinical Collaborator
- Jane A. Little, MD, Hematology, Director of Adult Sickle Cell Anemia Center
Funding
- Innovations in Clinical Research Award, Grant #2013126, Doris Duke Charitable Foundation
- National Science Foundation, Award #1552782, CAREER: Biomechanics of Red Blood Cell Adhesion and Deformability
- National Heart, Lung, and Blood Institute, National Institutes of Health, R01 HL133574. Standardized Monitoring of Cellular Adhesion to Improve Clinical Care in Sickle Cell Disease
Micro-engineering: Point-of-care platforms for hemoglobin disorders
More than 800 children are born with sickle cell anemia (the most common and severe version of hemoglobin disorders every day in Africa, and more than half of them die in childhood due to lack of diagnosis and early treatment. In the US, hemoglobin screening of newborns is mandated for early diagnosis, so that, monitoring and treatment can be started immediately, which has dramatically reduced hemoglobin disorder related mortality. However, this strategy has not been widely available in Africa and other third-world countries, due to limited resources.
Summary
Our goal is to reduce the footprint and enhance the accessibility of hemoglobin screening methods for newborns and adults by utilizing micro-engineered systems.
Clinical Collaborators
- Jane A. Little, MD, Hematology, Director of Adult Sickle Cell Anemia Center
- Connie Piccone, MD, Pediatric Hematology
Funding
- Belcher-Weir Family Pediatric Innovation Award from the Center for Clinical Research and Technology at University Hospitals Case Medical Center
Awards
- CWRU Team led by EMAE’s Graduate Student Yunus Alapan has won the first place in 2014 NASA Tech Briefs Create the Future Design Contest in Medical Category (October 2014). Yunus Alapan, EMAE graduate student and PhD candidate in CASE-BML, has won the first prize in Medical Category in 2014 NASA Tech Briefs Create the Future Design Contest. CWRU Team lead by Yunus utilized a microengineered design in developing HemeChip, a new device that can identify hemoglobin type in a drop of blood rapidly to diagnose hemoglobin disorders in newborns early.
- Our team, led by mechanical and aerospace engineering graduate student Yunus Alapan, has won the first prize and $150,000 in the Student Technology Prize for Primary Healthcare, a national and highly selective competition seeking innovations in health care delivery organized by the Center for Integration of Medicine and Innovative Technology.
Micro-engineering, musculoskeletal biology: Monitoring and management of joint and prosthesis health
Osteoarthritis causes significant disability among military personnel, including young individuals who suffered acute traumatic injury. Osteoarthritis is more common in military service personnel and veterans, and the affected ages are lower in these populations. On the other hand, a clinical challenge in evaluating painful joints stems from identifying infection or inflammation in either native or prosthetic joints. A consistent and standardized modality for monitoring and evaluation of joint health before and after development of joint diseases would directly benefit the veteran population.
Summary
We develop micro-systems that accurately assesses joint synovial fluid, which will help clinicians diagnose infection or inflammation quickly and monitor joint and prosthesis health reliably in military and veteran populations, as well as in general public.
Clinical Collaborator
- Glenn Wera, MD, Orthopaedic Surgery
Funding
- Steven Garverick Memorial Innovation Incentive Award
- The Advanced Platform Technology Center
- Louis Stokes Cleveland Veterans Affairs Medical Center
Micro-engineering: Microfluidic microengineered sensors for point-of-care applications
Quantitative measurement of the complex dielectric permittivity of a material versus frequency is a powerful monitoring technique with a broad range of applications including chemical analysis in the petroleum industry, soil moisture monitoring, pharmaceutical drug development and proteomics research for the study of molecular dynamics and protein interactions. These techniques are also powerful analytical tools in the biomedical field as label-free, non-destructive and real-time ways to study key molecular characteristics of biomaterials for potential applications in disease detection and clinical diagnosis.
Summary
We integrate microengineering, microfluidics and electronics to develop the next generation biomedical point-of-care sensing platforms.
Collaborators
- Pedram Mohseni, PhD, Associate Professor, CWRU BioMicroSystems Laboratory
- Michael Suster, PhD, Research Associate, CWRU BioMicroSystems Laboratory
Funding
- Case Western Reserve University
Making the smallest medical devices
Recent advances in microfabrication, microfluidics, microelectronics and tissue engineering have enabled the development of engineered cellular environments, paving the way for complex and scalable microphysiological systems and functional tissues. CASE-BML develops technologies for musculoskeletal research and clinically applicable solutions for regenerative medicine using advanced manufacturing technologies and microfabrication.
Summary
We develop new technologies and approaches to make the smallest medical devices of the future.