My work on “Enhancing sensitivity and specificity in rare cell capture microdevices with dielectrophoresis” was recently published in Biomicrofluidics, with co-authors Charlie Huang and Brian Kirby. This paper describes numerical simulations that identify microfluidic obstacle array geometries where dielectrophoersis (DEP) can be combined with immunocapture to increase the capture of target rare cells, such as circulating tumor cells (CTCs), while simultaneously repelling contaminating cells. These simulations build on our previous efforts that have shown that cancer cells exhibit a different DEP response than healthy blood cells, and lay the groundwork for the experimental study of hybrid DEP–immunocapture obstacle array microdevices.
Separately, I have also reported on “A transfer function approach for predicting rare cell capture microdevice performance” in Biomedical Microdevices. This work describes a numerical technique that extends our previously-reported computational fluid dynamics (CFD) simulations of rare cell transport and capture in microfluidic devices into larger, more complex geometries. This transfer function approach matches the full CFD simulation within 1.34% at a 74-fold reduction in computational costs, and the transfer function’s predictions for lateral displacement within complex reversing geometries were validated experimentally using particle tracking and polystyrene microspheres in a GEDI device.
Earlier this year, I joined the technical staff of the MIT Lincoln Laboratory, working in the Engineering Division‘s Structural and Thermal-Fluids Engineering Group. I’m splitting my time between research and engineering efforts, and am enjoying the exposure to new fields and exciting applications, while continuing to build on my work in microfluidics.
Smith JP, Kirby BJ. “A Transfer Function Approach for Predicting Rare Cell Capture Microdevice Performance”, Biomedical Microdevices, 17:53, 2015. DOI: 10.1007/s10544-015-9956-7.
Smith JP, Huang C, Kirby BJ. “Enhancing sensitivity and specificity in rare cell capture microdevices with dielectrophoresis”, Biomicrofluidics, 9:014116, 2015. DOI: 10.1063/1.4908049.
My paper entitled “Characterization of microfluidic shear-dependent epithelial cell adhesion molecule immunocapture and enrichment of pancreatic cancer cells from blood cells with dielectrophoresis” was recently published in the journal Biomicrofluidics. This paper describes my work on characterizing shear-dependent EpCAM immunocapture of pancreatic cancer cells enhanced by positive dielectrophoresis (DEP) and nonspecific adhesion of blood cells reduced by negative DEP. We evaluated capture probability as a function of shear stress, cell surface chemistry, and normal force using a capture probability model, and demonstrated that DEP can enhance immunocapture of cancer cells with lower EpCAM expression and that immunocapture purity can potentially be improved by repelling blood cells with negative DEP. This work informs the design of future hybrid DEP-immunocapture devices with increased CTC capture purity, which will facilitate subsequent functional and genetic analyses to elucidate cancer progression and develop more effective treatment options.
Huang C, Smith JP, Saha TM, Rhim AD, Kirby BJ. “Characterization of microfluidic shear-dependent epithelial cell adhesion molecule immunocapture and enrichment of pancreatic cancer cells from blood cells with dielectrophoresis,” Biomicrofluidics, 8(4): 044107, 2014. DOI
I also recently started as a Postdoctoral Research Staff Member at Lawrence Livermore National Laboratory in Livermore, CA in the Center for Bioengineering, Micro and Nano Technology Section of the Materials Engineering Division. I will be working on an acoustofluidics cell/particle separation project as well as a microfluidic nanoparticle synthesis project. I am very much enjoying NorCal weather and having weekends free!
Godla recently presented a talk entitled “Using Rare Cell Capture to Understand Metastasis” at the 13th International Summer School on Biocomplexity, Biodesign, and Bioinnovation in Istanbul, Turkey. The presentation highlighted recent work using GEDI immunocapture to isolate circulating tumor cells (CTCs) from a metastatic pancreatic cancer mouse model, with the goal of comparing genetic mutations in these CTCs with mutations found in the primary tumor and metastases. More information on the Summer School can be found here.
I recently traveled to Newport, RI to attend the Bioanalytical Sensors Gordon Research Seminar (at which I presented a talk and a poster), and the Bioanalytical Sensors Gordon Research Conference (at which I presented a poster). My presentations focused on my recent work on measuring the electrical properties of cancer cells and observing how these properties change in response to stimuli. Such measurements are important for robust, optimal operation of dielectrophoresis-based cell capture devices.
Marie Godla was recently awarded a fellowship to attend the 13th International Summer School on Biocomplexity, Bioinnovation, and Biodesign in Istanbul, Turkey in June 2014. This Summer School is sponsored by the NSF and co-sponsored by the IEEE EMB Society, the Department of Biomedical Engineering at University of Houston, the School of Biological and Health Systems Engineering at Arizona State University and the Bogazici University. Approximately 30 students from around the world were selected to attend. Additionally, to support travel to this conference, Marie was awarded a conference travel grant from Cornell University.
More information on the Summer School can be found here.
Chao “Charlie” Huang successfully defended his PhD thesis on characterization of microfluidic shear-dependent immunocapture and enrichment of cancer cells from blood cells with dielectrophoresis. Charlie’s thesis committee members included chair Brian J. Kirby (Mechanical and Aerospace Engineering), Susan Daniel (Chemical and Biomolecular Engineering), and Robert S. Weiss (Biomedical Sciences).
My paper entitled “In vivo fluorescence imaging of biomaterial-associated inflammation and infection in a minimally invasive fashion” recently got accepted for publication in Journal of Biomedical Materials Research A. This paper highlights the work I performed in Prof Andres Garcia lab at Georgia Tech before moving to Cornell. In this paper, we present a minimally invasive strategy for simultaneous, real-time monitoring of implant associated-aseptic inﬂammation by detecting ROS and bacterial infection by detecting NO released in the vicinity of the implant. This imaging modality has clinical translational potential and could be very beneﬁcial for the development of novel therapies to improve the performance of biomedical devices. Here is the link to the full paper: http://onlinelibrary.wiley.com/doi/10.1002/jbm.a.35162/abstract
Recently I also published 2 more papers in Lab on a chip and Biomedical Microdevices. The title of Lab on a chip paper is”Microfluidic-based patterning of embryonic stem cells for in vitro development studies“. In this paper, we developed a multicellular embryoid body fusion technique as a higher-throughput in vitro tool, compared to a manual assembly, to generate developmentally relevant embryonic patterns. The proposed microfluidic approach could be used to manipulate hundreds or more of individual embryonic cell aggregates in a rapid fashion, thereby allowing controlled differentiation patterns in fused multicellular assemblies to generate complex yet spatially controlled microenvironments. Here is the link to the full paper: http://pubs.rsc.org/en/content/articlelanding/2013/lc/c3lc50663k#!divAbstract
In the Biomedical Microdevices paper entitled “Single-cell analysis of embryoid body heterogeneity using microfluidic trapping array“, we examined the ability of a microfluidic cell trapping array to analyze the heterogeneity of cells comprising embryoid bodies during the course of early differentiation. The method described in the paper represents a novel approach for evaluating how heterogeneity is manifested in embryoid bodies cultures and may be used in the future to assess the kinetics and patterns of differentiation in addition to the loss of pluripotency. Here is the link to the full paper: http://link.springer.com/article/10.1007%2Fs10544-013-9807-3
I recently presented work in the Cornell Micro/Nanofluidics Laboratory on “Circulating tumor cell (CTC) cancer biomarkers using geometrically enhanced differential immunocapture (GEDI) microdevices” at the 2014 meeting of the Society for Laboratory Automation & Screening. In this poster presentation, I cover my work in the design and optimization of GEDI, as well as recent unpublished work by my colleagues in the Cornell Micro/Nanofluidics Lab. In addition to enjoying my own presentation and the various technical talks, I found SLAS2014’s career planning and networking resources to be a valuable part of the conference. A copy of the poster is available on my website.
My paper “Enrichment of prostate cancer cells from blood cells with a hybrid dielectrophoresis and immunocapture microfluidic system” was recently published in the journal Biomedical Microdevices. This paper describes my work on characterizing cancer cell enrichment from blood cells using a combination of dielectrophoresis (DEP) and immunocapture techniques. I showed that dielectrophoresis can enhance the capture of prostate cancer cells while reducing the nonspecific adhesion of peripheral blood mononuclear cells to immunocapture surfaces. This work informs the design of future hybrid DEP-immunocapture devices for high-purity rare cell capture.
Huang C, Liu H, Bander NH, Kirby BJ. “Enrichment of prostate cancer cells from blood cells with a hybrid dielectrophoresis and immunocapture microfluidic system,” Biomedical Microdevices, 15(6): 941-8, 2013. DOI
Recently, my paper “Characterization of a hybrid dielectrophoresis and immunocapture microfluidic system for cancer cell capture” was published in and featured on the cover of ELECTROPHORESIS.
This paper describes how characterization of adhesion of prostate cancer cells to immunocapture surfaces with and without dielectrophoresis (DEP) effects as a function of shear stress was performed in a Hele-Shaw flow cell. Gold interdigitated electrodes were deposited on a glass surface that was functionalized with a prostate-specific monoclonal antibody, J591; these electrodes applied an electric field gradient to attract prostate cancer cells to the immunocapture surface with positive DEP. This work demonstrates that DEP and immunocapture techniques can work synergistically to improve cancer cell capture performance, and it informs the design of future high-purity rare cell capture systems to facilitate genetic and pharmacological evaluation of cancer.
Huang C, S Santana, Liu H, Bander NH, Hawkins BG, Kirby BJ. ”Characterization of a hybrid dielectrophoresis and immunocapture microfluidic system for cancer cell capture,” Electrophoresis, 34(20): 2970-9, 2013. DOI