Browsing by Author "Sun, Chen"

Now showing 1 - 8 of 8
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    B-decay anomalies and scalar leptoquarks in unified Pati-Salam models from noncommutative geometry
    Aydemir, Ufuk; Minic, Djordje; Sun, Chen; Takeuchi, Tatsu (Springer, 2018-09-19)
    Motivated by possible scalar-leptoquark explanations of the recently reported B-decay anomalies, we investigate whether the required leptoquarks can be accommodated within models based on noncommutative geometry (NCG). The models considered have the gauge structure of Pati-Salam models, SU(4) x SU(2)(L) x SU(2)(R), with gauge coupling unification at a single scale. In one of the models, we find a unique scalar leptoquark with quantum numbers (3, 1, -1/3)(321), originating from a complex multiplet (6, 1, 1)(422), which can potentially explain the B-decay anomalies if its mass is on the order of a few TeV. The unification of couplings can be realized with the inclusion of a single step of intermediate symmetry breaking. The scalar leptoquark under consideration does not contribute to proton decay due to the absence of diquark couplings, as dictated by the underlying noncommutative geometry.
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    Constraining New Physics with Colliders and Neutrinos
    Sun, Chen (Virginia Tech, 2017-06-06)
    In this work, we examine how neutrino and collider experiments can each and together put constraints on new physics more stringently than ever. Constraints arise in three ways. First, possible new theoretical frameworks are reviewed and analyzed for the compatibility with collider experiments. We study alternate theories such as the superconnection formalism and non-commutative geometry (NCG) and show how these can be put to test, if any collider excess were to show up. In this case, we use the previous diboson and diphoton statistical excess as examples to do the analysis. Second, we parametrize low energy new physics in the neutrino sector in terms of non-standard interactions (NSI), which are constrained by past and proposed future neutrino experiments. As an example, we show the capability of resolving such NSI with the OscSNS, a detector proposed for Oak Ridge National Lab and derive interesting new constraints on NSI at very low energy (≲ 50 MeV). Apart from this, in order to better understand the NSI matter effect in long baseline experiments such as the future DUNE experiment, we derive a new compact formula to describe the effect analytically, which provides a clear physical picture of our understanding of the NSI matter effect compared to numerical computations. Last, we discuss the possibility of combining neutrino and collider data to get a better understanding of where the new physics is hidden. In particular, we study a model that produces sizable NSI to show how they can be constrained by past collider data, which covers a distinct region of the model parameter space from the DUNE experiment. In combining the two, we show that neutrino experiments are complementary to collider searches in ruling out models such as the ones that utilize a light mediator particle. More general procedures in constructing such models relevant to neutrino experiments are also described.
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    Electroporation-based delivery of cell-penetrating peptide conjugates of peptide nucleic acids for antisense inhibition of intracellular bacteria
    Ma, Sai; Schroeder, Betsy; Sun, Chen; Loufakis, Despina N.; Cao, Zhenning; Sriranganathan, Nammalwar; Lu, Chang (The Royal Society of Chemistry, 2014-08-14)
    Cell penetrating peptides (CPPs) have been used for a myriad of cellular delivery applications and were recently explored for delivery of antisense agents such as peptide nucleic acids (PNAs) for bacterial inhibition. Although these molecular systems (i.e. CPP–PNAs) have shown ability to inhibit growth of bacterial cultures in vitro, they show limited effectiveness in killing encapsulated intracellular bacteria in mammalian cells such as macrophages, presumably due to difficulty involved in the endosomal escape of the reagents. In this report, we show that electroporation delivery dramatically increases the bioavailability of CPP–PNAs to kill Salmonella enterica serovar Typhimurium LT2 inside macrophages. Electroporation delivers the molecules without involving endocytosis and greatly increases the antisense effect. The decrease in the average number of Salmonella per macrophage under a 1200 V cm_1 and 5 ms pulse was a factor of 9 higher than that without electroporation (in an experiment with a multiplicity of infection of 2 : 1). Our results suggest that electroporation is an effective approach for a wide range of applications involving CPP-based delivery. The microfluidic format will allow convenient functional screening and testing of PNA-based reagents for antisense applications.
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    Electroporation-delivered fluorescent protein biosensors for probing molecular activities in cells without genetic encoding
    Sun, Chen; Ouyang, Mingxing; Cao, Zhenning; Ma, Sai; Alqublan, Hamzeh; Sriranganathan, Nammalwar; Wang, Yingxiao; Lu, Chang (The Royal Society of Chemistry, 2014-08-08)
    Fluorescent protein biosensors are typically implemented via genetic encoding which makes the examination of scarce cell samples impractical. By directly delivering the protein form of the biosensor into cells using electroporation, we detected intracellular molecular activity with the sample size down to ~100 cells with high spatiotemporal resolution.
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    Immunomagnetic separation of tumor initiating cells by screening two surface markers
    Sun, Chen; Hsieh, Yuan-Pang; Ma, Sai; Geng, Shuo; Cao, Zhenning; Li, Liwu; Lu, Chang (Springer Nature, 2017-01-11)
    Isolating tumor initiating cells (TICs) often requires screening of multiple surface markers, sometimes with opposite preferences. This creates a challenge for using bead-based immunomagnetic separation (IMS) that typically enriches cells based on one abundant marker. Here, we propose a new strategy that allows isolation of CD44(+)/CD24(-) TICs by IMS involving both magnetic beads coated by anti-CD44 antibody and nonmagnetic beads coated by anti-CD24 antibody (referred to as two-bead IMS). Cells enriched with our approach showed significant enhancement in TIC marker expression (examined by flow cytometry) and improved tumorsphere formation efficiency. Our method will extend the application of IMS to cell subsets characterized by multiple markers.
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    Microfluidic technology for cellular analysis and molecular biotechnology
    Sun, Chen (Virginia Tech, 2016-03-04)
    Microfluidics, the manipulation of fluids at nanoliter scale, has emerged to offer an ideal platform for biological analysis of a low number of cells. The technological advances in microfluidics have allowed both forming of valves, mixers and pumps and integrating of optic and electronic components into microfluidic devices to construct complete and functional systems. In this dissertation, I present novel microfluidic techniques and their applications in cellular probes delivery, cell separation and epigenetic study. In the first part of the dissertation, electroporation is implemented on microfluidic platform to generate uniform delivery of "exposed" nanoparticle or protein into cells. In contrast to endocytosis, electroporation is a physical method to breach cell membrane and does not involve vesicle encapsulation of delivered probes, which means these probes have exposed surface in the cytosol. Such trait enables the use of delivered nanoparticle and protein for intracellular targeting of native biomolecules. Laser-induced fluorescent microscopy was used for single particle illuminating to track single molecules in cells. Microfluidic device provide integrated platform for conducting electroporation, cell culture and imaging. In the second part, microfluidic immunomagnetic cell separation is introduced. I showed two new approaches to enhance immunomagnetic cell separation based on (1) uniquely microfabricated paramagnetic patterns inside separation channels; and (2) using combination of nonmagnetic beads and magnetic beads for selection of tumor initiating cells based on two markers of opposite preference in one step. Enhancement in cell isolation (high capture efficiency or high selection purity) is experimentally observed and the former is explained by computational model. In the final part of the dissertation, microfluidic device incorporating valves and mixers for sensitive study of chromosome conformation is presented. This device has small reaction chamber minimizing sample requirement, and allows multiple steps of biological analysis in a single chip avoiding sample loss during sample transfer. Several orders of magnitude improved detection sensitivity is achieved with our microfluidics based method. I envision all novel techniques discussed in this dissertation have great potential in application of disease prognosis, diagnosis and treatment.
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    Paramagnetic Structures within a Microfluidic Channel for Enhanced Immunomagnetic Isolation and Surface Patterning of Cells
    Sun, Chen; Hassanisaber, Hamid; Yu, Richard; Ma, Sai; Verbridge, Scott S.; Lu, Chang (Nature, 2016-07-08)
    In this report, we demonstrate a unique method for embedding magnetic structures inside a microfluidic channel for cell isolation. We used a molding process to fabricate these structures out of a ferrofluid of cobalt ferrite nanoparticles. We show that the embedded magnetic structures significantly increased the magnetic field in the channel, resulting in up to 4-fold enhancement in immunomagnetic capture as compared with a channel without these embedded magnetic structures. We also studied the spatial distribution of trapped cells both experimentally and computationally. We determined that the surface pattern of these trapped cells was determined by both location of the magnet and layout of the in-channel magnetic structures. Our magnetic structure embedded microfluidic device achieved over 90% capture efficiency at a flow velocity of 4 mm/s, a speed that was roughly two orders of magnitude faster than previous microfluidic systems used for a similar purpose. We envision that our technology will provide a powerful tool for detection and enrichment of rare cells from biological samples.
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    Thermal loading in flow-through electroporation microfluidic devices
    del Rosal, Blanca; Sun, Chen; Loufakis, Despina N.; Lu, Chang; Jaque, Daniel (The Royal Society of Chemistry, 2013-05-15)
    Thermal loading effects in flow-through electroporation microfluidic devices have been systematically investigated by using dye-based ratiometric luminescence thermometry. Fluorescence measurements have revealed the crucial role played by both the applied electric field and flow rate on the induced temperature increments at the electroporation sections of the devices. It has been found that Joule heating could raise the intra-channel temperature up to cytotoxic levels (>45 °C) only when conditions of low flow rates and high applied voltages are applied. Nevertheless, when flow rates and electric fields are set to those used in real electroporation experiments we have found that local heating is not larger than a few degrees, i.e. temperature is kept within the safe range (<32 °C). We also provide thermal images of electroporation devices from which the heat affected area can be elucidated. Experimental data have been found to be in excellent agreement with numerical simulations that have also revealed the presence of a non-homogeneous temperature distribution along the electroporation channel whose magnitude is critically dependent on both applied electric field and flow rate. Results included in this work will allow for full control over the electroporation conditions in flow-through microfluidic devices.