Smith publishes in Biomicrofluidics, Biomedical Microdevices; joins MIT Lincoln Laboratory

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.

Kirbylab circulating tumor cell biomarker research presented at Lab Automation 2014

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.

Two papers on cell collision and capture dynamics in GEDI devices published

We have recently published two papers on the collision and capture dynamics of circulating tumor cells (CTCs) and other rare cells in geometrically enhanced differential immunocapture (GEDI) microdevices.

The first paper, “Cell capture simulations for the optimization of microfluidic rare cell immunocapture devices” was published in Biomedical Microdevices by James Smith, Timothy Lannin, Yusef Syed, S Santana, and Brian Kirby.  We use computational fluid dynamics (CFD), particle advection, and exponential-based cell capture simulations to identify capture-optimized GEDI geometries.  We show that it’s possible to select a geometry which maximizes capture efficiency while rejecting small contaminating cells via infrequent collisions and large contaminating cells via high shear stress; the accompanying figure shows this as capture probability vs. particle diameter in an example GEDI geometry.

Capture probability vs. cell diameter in a GEDI device
The probability of capturing cells in a GEDI device is shown vs. cell diameter; capture probability is a function of collision frequency, the duration of cell-obstacle contact, and the local shear stress. Shaded regions represent standard deviation for N = 30,000 simulated cells.

We have also published a paper in Physical Review E, “Transport and collision dynamics in periodic asymmetric obstacle arrays: rational design of microfluidic rare cell immunocapture devices“, by Jason Gleghorn, James Smith, and Brian Kirby. The paper describes work using CFD and ballistic collision dynamics simulations to better understand how to bring rare cells into contact with an antibody-terminated capture surface in a GEDI device, and describes previously unrecognized collision mode structures and differential size-based collision frequencies that emerge from these arrays.

Copies of both of these papers are available on my website.

Smith’s rare cell capture simulations published in Biomedical Microdevices

I recently published a peer-reviewed article on “Cell capture simulations for the optimization of microfluidic rare cell immunocapture devices” in Biomedical Microdevices, along with my colleagues Tim Lannin, Yusef Syed, S Santana, and Brian Kirby. We detail a coupled computational fluid dynamics (CFD), particle advection, and experimentally-informed cell capture simulation to identify capture-optimized geometrically enhanced differential immunocapture (GEDI) designs.  I show that it is possible to select a geometry which maximizes capture efficiency while rejecting small contaminating cells via infrequent collisions and large contaminating cells via high shear stress.

You can read the abstract and view a PDF on my website.

Smith’s Captura Diagnostics wins $25,000 Grants For Growth award to develop commercial cell capture prototype

I have recently founded a startup company, Captura Diagnostics, Inc., to commercialize microfluidic rare cell capture technologies for applications in research and clinical care. Captura currently consists of myself, handling the initial technical work, and Max Dougherty, who is managing the business; Captura is advised by Brian Kirby.  It is our hope that Captura will facilitate the widespread adoption of technologies like GEDI and others by researchers and clinicians using rare cells (such as CTCs) to better understand disease progression, to develop new drugs, and for patient-specific treatments.

I’m excited to announce that Captura has won a $25,000 “Grants For Growth” proof of concept grant. Awarded by the CenterState Corporation for Economic Opportunity and funded by New York State, this award will support the development and fabrication of a prototype for a mass-produced rare cell capture device and significantly increases Captura’s ability to secure additional rounds of funding.  Captura is pursuing additional support from the NSF and NIH Small Business Innovation in Research (SBIR) programs and other sources, and is applying for residency in Cornell University’s McGovern Center for Venture Development in the Life Sciences incubator.

Smith passes Admission to Candidacy exam

I successfully completed my “A exam,” defending my thesis proposal and becoming a PhD Candidate.  I was also awarded a Masters of Science degree in Mechanical Engineering as part of the exam.  My committee was chaired by my advisor, Prof. Brian Kirby, and also included Prof. Don Koch, and Dean Lance Collins (as proxy for Prof. Pete Diamessis, who is on sabbatical). You can find a copy of my presentation on my website.

Smith reports on cell capture and growth research in Tissue Engineering

In a collaboration between the Cornell Micro/Nanofluidics Lab and the Biological Surface Engineering and Microfluidics Laboratory at Northeastern University, we recently published on “Microfluidic enrichment of mouse epidermal stem cells and validation of stem cell proliferation in vitro,” in the journal Tissue Engineering C with Beili Zhu and Shashi Murthy of Northeastern University and Brian Kirby at Cornell.  We isolate bulge stem cells from mice in under 30 minutes using a microfluidic platform, and show that these cells remain viable and grown in culture.  My CFD simulations, detailed in this paper, led to an eight-fold improvement in sample purity as compared to previous stem cell isolation devices.

The article’s abstract and a downloadable PDF are available on my publications page.

Microfluidic transport in microdevices for rare cell capture

We recently published a review in a special “Microfluidics and Miniaturization” issue of Electrophoresis. This work was a collaboration between myself, Jason, Alex, Steven, and Brian.  Brian and Steven contributed knowledge on rare cell adhesion, Alex discussed fluid mechanics at the microscale, and Jason and I reviewed device designed strategies.

Pathline
An obstacle array is used to induce cross-streamline motion, bringing target cells into contact with an immunocapture surface, while smaller non-target cells have relatively few collisions (represented by stars).

The article reviews biorheology, rare cell surface markers and adhesion models, as well as general transport phenomena at the microscale.  Several design strategies, including micromixers, porous filtration systems, and obstacle arrays, are presented in a transport context.  A key conclusion is that advection (i.e., motion of the fluid itself) dominates diffusion in most rare cell capture devices; a successful device is designed not by maximizing the ratio of surface area to volume, but by inducing cross-streamline motion to bring cells into contact with a capture surface.

This review summarizes the knowledge we have gained developing the GEDI microdevice, and we hope that other researchers will find it useful in the development of their own rare cell capture devices. A copy of our review is available on my website.

Smith presented cell capture simulation advances at APS-DFD 2012

I presented my recent work on cell capture simulations at the Fall meeting of the American Physical Society’s Division of Fluid Dynamics (APS DFD) in San Diego. During this podium presentation, I detailed a reduced order model for predicting the adhesion of rare cells, such as circulating tumor cells (CTCs) to antibody-functionalized obstacle surfaces in microdevices. This work builds on my past projects involving particle collision dynamics and will facilitate the design of a new generation of rare cell capture microdevices.

Smith wins Poster Merit Award at 2010 GRC on Microfluidics

I recently attended the 2011 Gordon Research Conference on the Physics and Chemistry of Microfluidics in Waterville Valley, NH.  I presented a poster on “Transport and collision dynamics in GEDI cell capture microdevices” at both the Gordon Research Seminar, organized and run by students and preceding the conference, and at the Gordon Research Conference itself.  I’m pleased to announce that my poster was one of four selected during the Conference to receive a Poster Merit Award, along with a small prize sponsored by Cambridge University Press. A copy of the poster is available on my website.