skip to main content

Search for: All records

Creators/Authors contains: "Parajuli, Ritesh"

Note: When clicking on a Digital Object Identifier (DOI) number, you will be taken to an external site maintained by the publisher. Some full text articles may not yet be available without a charge during the embargo (administrative interval).
What is a DOI Number?

Some links on this page may take you to non-federal websites. Their policies may differ from this site.

  1. Abstract

    Autologous cell therapy depends on T lymphocyte expansion efficiency and is hindered by suboptimal interactions between T cell receptors (TCR) and peptide‐MHC molecules. Various artificial antigen presenting cell systems that enhance these interactions are often labor‐intensive, fabrication costly, highly variable, and potentially unscalable toward clinical setting. Here, 3D centrifugation‐enabled priming of T cell immune‐synapse junctions is performed to generate tight T cell–Dynabead aggregates at a rate 200‐fold faster than that of conventional 24‐h bulk shaking. Furthermore, by forming T cell–Dynabead aggregates in the starting culture, two‐ to sixfold greater T cell expansion is achieved over conventional T cell expansion for cancer patient‐derived primary T cells while limiting over‐activation. Creating 3D T cell–Dynabead aggregates as the “booster” material enables highly efficient polyclonal T cell expansion without the need for complex surface modification of artificial antigen‐presenting cells (APCs). This method can be modularly adapted to existing T cell expansion processes for various applications, including adoptive cell therapies (ACTs).

    more » « less
    Free, publicly-accessible full text available December 1, 2024
  2. null (Ed.)
    We demonstrate a label free and high-throughput microbubble-based acoustic microstreaming technique to isolate rare circulating cells such as circulating cancer associated fibroblasts (cCAFs) in addition to circulating tumor cells (CTCs) and immune cells ( i.e. leukocytes) from clinically diagnosed patients with a capture efficiency of 94% while preserving cell functional integrity within 8 minutes. The microfluidic device is self-pumping and was optimized to increase flow rate and achieve near perfect capturing of rare cells enabled by having a trapping capacity above the acoustic vortex saturation concentration threshold. Our approach enables rapid isolation of CTCs, cCAFs and their associated clusters from blood samples of cancer patients at different stages. By examining the combined role of cCAFs and CTCs in early cancer onset and metastasis progression, the device accurately diagnoses both cancer and the metastatic propensity of breast cancer patients. This was confirmed by flow cytometry where we observed that metastatic breast cancer blood samples had significantly higher percentage of exhausted CD8 + T cells expressing programmed cell death protein 1 (PD1), higher number of CD4 + T regulatory cells and T helper cells. We show for the first time that our lateral cavity acoustic transducers (LCATs)-based approach can thus be developed into a metastatic propensity assay for clinical usage by elucidating cancer immunological responses and the complex relationships between CTCs and its companion tumor microenvironment. 
    more » « less