Research

Diagnostic tool for tick-borne infections

Funded by NIH 1R01AI174300-01: The incidence of tick-borne diseases (TbD) is increasing and is expected to continue to increase, in large part due to global climate change. Our goal is to create a continuous, rapid, sensitive, and label-free diagnostic tool for tick-borne diseases (TbD). Our hypothesis is based on our previously published studies showing that differential expression of proteins on bioparticles can be leveraged to detect infections and parasites via an electrokinetic technique, dielectrophoresis (DEP) Two main reasons are: (1) people are encroaching more into the habitats where ticks live, and (2) as climate changes, tick ranges are expanding; thus, TbD cases are expected to increase in the future, becoming an even greater problem. Currently, Lyme disease is the most prevalent vector-borne disease in the US, with estimates of ~476,000 cases/year.

Additionally, we are also evaluating if Rickettsia spp. could be detected early on through an internal RSA grant

    

Extraction of rare earth elements (REE) using biosorbent

Funded by NSF 1500815: This work presents the dielectric characterization of rare earth elements (REEs) biosorption by Cupriavidus necator using dielectrophoretic crossover frequency measurements. Traditional means of characterizing biomass for biosorption are limited and time-consuming. In this research, for the first time, we present an electrokinetic method termed dielectrophoresis (DEP) for the characterization of biosorption (uptake) of rare earth elements (REEs) by gram-negative bacteria - Cupriavidus necator. Quantified dielectric properties of native Cupriavidus necator (REE-) and those exposed to rare earth elements (REE+), europium, neodymium, and samarium revealed a substantial change in the surface characteristics of the Cupriavidus necator after exposure to the REE solution. The response of C. necator to changes in REE exposure is substantially different for europium but similar between neodymium and samarium. Statistically, the dielectric signatures of both the REE+ and REE- groups were significantly different, proving that the REEs were absorbed by the bacteria. This research will revolutionize and impact the researchers and industrialists in the field of biosorption, seeking economical, greener, and sustainable means to recover REEs.

Breast cancer detection via liquid biopsy

Noncommunicable diseases (NCDs) kill more than 36 million people annually, representing 63% of global deaths. Breast cancer, a subset of NCDs, accounts for over 500,000 of these deaths, with an incidence of about 1.1 million new cases being reported per year. Peripheral blood mononuclear cells (PBMCs) are specialized immune cells produced from hematopoietic stem cells (HSC). They actively surveil for any signs of infection, foreign invaders, and abnormal or aberrant cells associated with diseases. Numerous inherent interactions between PBMCs and proliferating cancer cells facilitate cellular communication, inducing alterations in the composition of PBMCs. These subtle alterations can be detected using dielectrophoresis. The ultimate objective is to apply this knowledge in a clinical setting to achieve non-invasive early detection of breast cancer while minimizing the occurrence of false positives and negatives commonly associated with standard screening methods like mammography. To realize our long-term goal, we are probing the dielectric properties of the PBMCs from FVB/N MMTV-PyMT+ (carcinoma, PyMT-PBMC) and FVB/N (wild-type, WT-PBMC) age-matched mice at 4+ weeks using the dielectrophoresis on a microfluidic platform. The central hypothesis of this research is that the changes triggered in the subcellular components, such as the cytoskeleton, lipid bilayer membrane, cytoplasm, focal adhesion proteins, and extracellular matrix (ECM) at the onset of carcinoma, regulate dielectric properties (conductivity, σ, and permittivity, ε), thus affecting the bioelectric signals that aid in the detection of breast cancer. 

Tenogenically differentiating mesenchymal stem cells

Tendons are collagenous musculoskeletal tissues that connect muscles to bones and transfer the forces necessary for movement. Tendons are susceptible to injury and heal poorly, with long-term loss of function. Mesenchymal stem cell (MSC)--based therapies are a promising approach for treating tendon injuries. Still, they are challenged by the difficulties of controlling stem cell fate and generating homogenous populations of stem cells optimized for tenogenesis (differentiation toward tendon). To address this issue, we aim to explore methods that can be used to identify and ultimately separate tenogenically differentiated MSCs from non-tenogenically differentiated MSCs. In this study, baseline and tenogenically differentiating murine MSCs were characterized for dielectric properties (conductivity and permittivity) of their outer membrane and cytoplasm using a dielectrophoretic (DEP) crossover technique. Experimental results showed that unique dielectric properties distinguished tenogenically differentiating MSCs from controls after three days of tenogenic induction. Cell responses at the crossover frequency, cell morphology, and shell models showed that changes indicative of early tenogenesis could be detected in the dielectric properties of MSCs as early as three days into differentiation. Differences in dielectric properties with tenogenesis indicate that the DEP-based label-free separation of tenogenically differentiating cells is possible and avoids the complications of current label-dependent flow cytometry-based separation techniques. Overall, this work illustrates the potential of DEP to generate homogeneous populations of differentiated stem cells for applications in tissue engineering and regenerative medicine.

 

Dielectric Changes of Cells Under Simulated Microgravity 

During spaceflight, NASA observed that microgravity could lead to a 1-1.5% monthly loss in bone mineral density, alongside detrimental effects on muscles, the neuro-vestibular system, the heart, and other vital organs. Understanding these effects is crucial, yet sending samples to space is costly and time-consuming. To overcome this, our lab uses a 2D clinostat to simulate microgravity on Earth, studying the behavior of RBCs from human pancreatic cancer patients, breast cancer mice, HL-60 cells, and other cancer cells. We employ the DEP crossover technique to measure changes in cell behavior, revealing significant variations in membrane permittivity and conductivity between Earth and microgravity conditions. Excitingly, we are also developing a 3D clinostat that rotates samples in two directions simultaneously, enhancing our ability to study the effects of microgravity.