L.S.L. Cheung

The University of Arizona, Tucson, AZ, United States

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Publications (11)3.22 Total impact

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    ABSTRACT: Dynamic states of cancer cells moving under shear flow in an antibody-functionalized microchannel are investigated experimentally and theoretically. A simplified physical model was adopted to analyze the cell motion; it features a rigid sphere, with receptors on its surface, moving above a solid surface with distributed ligands. The cell motion is described by the Langevin equation where the hydrodynamic interactions, gravitational drift force, receptor-ligand binding force, and thermal fluctuations are all taken into account. The receptor-ligand bonds are modeled as Hookean springs. In this study, three dynamic states of cell motion have been identified: (i) free motion, (ii) rolling adhesion, and (iii) firm adhesion depending on the flow shear rate. The numerical simulations allow exploring effects of numerous parameters such as cell-receptor and surface-ligand density.
    Micro Electro Mechanical Systems (MEMS), 2011 IEEE 24th International Conference on; 02/2011
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    ABSTRACT: The lifetime of microfluidic devices depends on their ability to maintain flow without interruption. Certain applications require microdevices for transport of liquids containing particles. However, microchannels are susceptible to blockage by solid particles. Therefore, in this study, the phenomenon of interest is the formation and growth of clusters on a microchannel surface in the flow of a dilute suspension of hard spheres. Based on the present experiments, aggregation of clusters was observed for particle-laden flows in microchannels with particle void fraction as low as 0.001 and particle diameter to channel height ratio as low as 0.1. The incipience and growth of a single cluster is discussed, and the spatial distribution and time evolution of clusters along the microchannel are presented. Although the cluster size seems to be independent of location, more clusters are found at the inlet/outlet regions than in the microchannel center. Similarly as for an individual cluster, as long as particle–cluster interaction is the dominant mode, the total cluster area in the microchannel grows almost linearly in time. The effects of flow rate, particle size, and concentration are also reported. KeywordsMicrochannel suspension flow–Particle aggregation–Cluster formation and growth
    Microfluidics and Nanofluidics 01/2011; 10(3):661-669. · 3.22 Impact Factor
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    ABSTRACT: The attachment and detachment of target cancer cells from homogeneous and binary mixtures in antibody-functionalized microchannels have been studied experimentally. Under the same intermediate flow rate, the attachment rate was found to be higher, and detachment flow rate was lower, for cell lines expressing the target receptor at a higher level. For cells that do not express the target receptor, the attachment rate was much lower but did not diminish, due to non-specific binding, and the detachment rate was much higher. The bio-functional microfluidic system performance in selectively isolating target cells from binary mixtures is quantitatively characterized. While the system sensitivity is typically very high, almost 100%, the specificity is lower than 90%. Applying a unique flow scheme of a slow flow rate, for maximum capture of target cells, followed by a faster flow rate, for maximum removal of non-target cells, the specificity is enhanced to levels above 95%, even for mixtures with target cells present at 1:1,000 relative concentration ratio.
    01/2011;
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    ABSTRACT: The system performance of an antibody-functionalized microchamber array, developed for selectively binding target cancer cells, is quantitatively characterized. The devices are designed to allow accurate counting of loaded and captured cells from heterogeneous suspensions. Specific interaction between cancer cell receptors and immobilized surface ligands has been demonstrated under static conditions. Performance measures such as specificity, sensitivity and accuracy are uniquely defined and experimentally evaluated. Several cell mixtures have been tested, and the quantitative system performance criteria are reported as a function of cell concentrations in the tested suspensions. These criteria provide a critical quantitative basis for a comparison among different systems aimed at selectively isolating target bio-species from complex mixtures.
    Micro Electro Mechanical Systems (MEMS), 2010 IEEE 23rd International Conference on; 02/2010
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    ABSTRACT: Cluster dynamics in microchannels due to flow of dilute suspensions of polystyrene spherical particles has been studied experimentally. Cluster-cluster interaction as well as the functional dependence of cluster growth rate on several control parameters has been studied. Destructive, e.g. cluster collision, and constructive modes, e.g. cluster merging, of cluster-cluster interaction have been observed. Cluster growth rate with time is found to increase with either particle concentration or shear strain rate, and decrease with channel-height to particle-diameter ratio.
    Micro Electro Mechanical Systems, 2009. MEMS 2009. IEEE 22nd International Conference on; 03/2009
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    ABSTRACT: The effect of flow acceleration, rather than just the flow rate, on the response of an attached cancer cell is for the first time reported. Selective binding of prostate cancer cells to a surface functionalized with anti-N-cadherin antibodies utilizing a microfluidic system under flow conditions has been studied. Here, the behavior of a captured cell under a time-dependent flow field is investigated experimentally and numerically. Under slowly increasing flow rate, the cell deformation is more pronounced resulting in lower drag force on attached cells. Furthermore, the contact area between the cell and the functionalized surface is larger, potentially enhancing the cell adhesion force. Consequently, a higher flow rate is required to detach cells exposed to such a flow field. Numerical simulations have been utilized in effort to quantify the required detachment force. The results confirm that to obtain a similar shear stress, a higher flow rate is needed for attached cells under lower flow acceleration.
    Micro Electro Mechanical Systems, 2009. MEMS 2009. IEEE 22nd International Conference on; 03/2009
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    ABSTRACT: polydimethylsiloxane (PDMS) based microsystems have successfully been fabricated and characterized for studying protein crystals utilizing both UV-visible spectroscopy and X-ray crystallography. Transmittance tests have been conducted with PDMS and glass substrates; the measurements indicate that in PDMS, unlike glass, the emerging intensity is higher than 50% of the incident intensity as long as the total optical path is shorter than 100 mum. Indeed, both the UV-visible spectrum and X-ray diffraction of a protein crystal enclosed in a PDMS device are almost identical to those of the crystal alone. Hence, PDMS is suitable as substrate material in device fabrication to study protein crystals. In glass, however, the UV-visible spectrum is significantly distorted and the X-ray diffraction pattern is rather weak resulting in poor signal to noise ratio. Furthermore, microsystems integrated with micro- channels allowing continuous exchange of buffer solution around the protein crystals have been tested; this would greatly enhance the potential to induce, trap and characterize functional states in proteins.
    Micro Electro Mechanical Systems, 2007. MEMS. IEEE 20th International Conference on; 01/2007
  • Man Lee, Luthur Siu Lin Cheung, Yi-Kuen Lee, Yitshak Zohar
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    ABSTRACT: A microchannel heat sink, integrated with pressure and temperature microsensors, is fabricated to study convective boiling under uniform heat flux boundary condition. Utilizing a wafer bond and etch back technology, the heat source, temperature and pressure sensors are separated from the fluid flow by a membrane only 1.5μm in thickness; thus, allowing good control of the thermal boundary conditions. Temperature and pressure distributions for various power levels and flow rates are measured while, simultaneously, the flow patterns are recorded. Single-phase flow results, compared with numerical simulations, confirm that the heat flux boundary condition is indeed nearly uniform. The sensor arrays, particularly for two-phase flow, provide the spatial and temporal dependence of both the temperature and pressures fields.
    ASME 4th International Conference on Nanochannels, Microchannels, and Minichannels; 01/2006
  • Man Lee, L. S. L. Cheung, Yi-Kuen Lee, Y. Zohar
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    ABSTRACT: A thermal microsystem, integrated with pressure and temperature microsensors, is fabricated to study convective boiling under nearly uniform heat flux boundary condition. The temperature and pressure distribution along the microchannel is measured correspondingly. The pressure increases with input power when two phase flow develops. A pressure peak appears at the location of liquid-vapor interface region. The transient temperature and pressure fluctuation is also measured. The dominant frequencies of the temperature and pressure fluctuation are the same values at the liquid-vapor interface region and this dominant frequencies increase with input power. Simultaneously, the qualitative visualizations of the evolving flow patterns have been correlated with the quantitative temperature and pressure measurements.
    01/2006;
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    ABSTRACT: Microchannels are susceptible to blockage by solid particles. Based on the present experiments, aggregation of clusters was observed for flow of liquid with 0.01 volume concentration of polystyrene particles, about 1.5µm in nominal diameter, through a microchannel 15µm high. The phenomenon of interest is the formation and growth of clusters in the flow of a dilute suspension of hard spheres. In general, the clusters initially grow almost linearly in time under various conditions. The spatial distribution and time evolution of clusters along the microchannel have been characterized. The effects of flow rate, volume fraction and channel-height to particle-diameter ratio are discussed as well. INTRODUCTION During multi-phase suspension flows adhesive particulates were identified as a leading cause of failure in fluidic microdevices [1]. Among many, one of the possible mechanisms for clustering is the probable occurrence of large local particle concentration enough to result in blocking of microchannels [2]. Despite their importance, the physical mechanisms responsible for clogging of microchannels are exceptionally complicated and poorly understood [3, 4]. Model descriptions of clogging often focus on different length scales than do typical experimental investigations and sometimes prove useful in understanding the clustering phenomena [5]. Particle capture by a substrate surface was examined with a model using a 'frozen deposit' assumption [6]. Shear flow of particulate suspension was analyzed using a kinetic clustering model and direct numerical simulations [7]. In the work, the effects of flow rate, particle size and concentration on cluster formation and growth have experimentally been investigated. DEVICE FABRICATION AND EXPERIMENTAL SETUP USED PDMS microchannels, capped by oxidized silicon wafers, have been fabricated; each is about H=15µm high, W=1mm wide and L=3cm long. Suspensions of polystyrene particles D=1.5 or 5µm in diameter were forced through the microchannels using a syringe pump. All experiments were conducted under a microscope equipped with a CCD camera, connected to a DVD recorder, to facilitate video recording and analysis. A picture of a packaged device, with a schematic of the experimental set-up, is shown in Figure 1.
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    ABSTRACT: Cadherins make up a family of cell adhesion molecules, and one cadherin sub-type only interacts with its counter receptor. Cancer cells typically down-regulate E-cadherin and up-regulate N-cadherin. Hence, a microchannel-based system is devel-oped, with immobilized anti-N-cadherin antibodies, for highly specific capture of prostate cancer cells under both static (no-flow) and dynamic (flow) conditions. The maximum number of detached cells, after capture, is found to depend not only on the flow-induced shear stress but also on the rate of change of the applied shear stress. INTRODUCTION Circulating tumor cells (CTCs) have been identified in peripheral blood from cancer patients, and are probably the origin of intractable metastatic disease [1]. These CTCs are very rare in blood and, thus, their isolation presents a formidable technical challenge [2]. Nonetheless, these cells represent a potential alternative to invasive biopsies for monitoring of non-haematologic cancers [3]; hence, the ability to characterize circulating tumor cells could further the discovery of cancer biomark-ers and enhance the understanding of metastasis. Current strategies for isolating cancer cells circulating in the blood stream are still limited to complex analytic techniques that generate very low yield and purity [4]. Fluidic microsystems provide unique opportunities for cell sorting and rare-cell detection. Indeed, the capture of tumor cells has been demonstrated using an anti-body-based platform in a microdevice [5]. Microchannels have been functionalized with antibodies to capture target cells [6]. In a landmark study, using similar anti-body coating, a microchannel with microposts has been developed for selective sepa-ration of viable circulating tumor cells from whole blood samples [7]. Recently, the attachment/detachment of cells on modified microchannel surfaces has been re-ported, including a theoretical model for fitting the experimental detachment data [8]. Here, we develop a cadherin-based microsystem to selectively capture prostate cancer cells. DEVICE FABRICATION AND CHARRACTERIZATION A schematic cross-section of the device fabrication process is shown in Fig. 1a. Microchannels etched in silicon wafers are capped by glass wafers, and the immuno-assay used for derivatizing the microchannel surface with antibodies is described elsewhere [9]. The bio-activity of the antibody coating is tested by incubating Cy3-labelled antigens in 1×PBS. The observed red light emitted from the labeled anti-gens, bound to the antibodies, indicate the coating bio-activity. A picture of a pack-aged device is shown in Fig. 1b next to an image of the emitted red light.