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  1. Abstract

    Cryopreservation by vitrification has far-reaching implications. However, rewarming techniques that are rapid and scalable (both in throughput and biosystem size) for low concentrations of cryoprotective agent (CPA) for reduced toxicity are lacking, limiting the potential for translation. Here, we introduce a joule heating–based platform technology, whereby biosystems are rapidly rewarmed by contact with an electrical conductor that is fed a voltage pulse. We demonstrate successful cryopreservation of three model biosystems with thicknesses across three orders of magnitude, including adherent cells (~4 µm),Drosophila melanogasterembryos (~50 µm) and rat kidney slices (~1.2 mm) using low CPA concentrations (2–4 M). Using tunable voltage pulse widths from 10 µs to 100 ms, numerical simulation predicts that warming rates from 5 × 104to 6 × 108 °C/min can be achieved. Altogether, our results present a general solution to the cryopreservation of a broad spectrum of cellular, organismal and tissue-based biosystems.

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  2. Ferromagnetic Co 35 Fe 65 , Fe, Co, and Ni nanowires have high saturation magnetizations ( M s ) and magnetic anisotropies, making them ideal for magnetic heating in an alternating magnetic field (AMF). Here, Au-tipped nanowires were coated with polyethylene glycol (PEG) and specific absorption rates (SAR) were measured in glycerol. SAR increased when using metals with increasing M s (Co 35 Fe 65 > Fe > Co > Ni), reaching 1610 ± 20 W g −1 metal at 1 mg metal per ml glycerol for Co 35 Fe 65 nanowires using 190 kHz and 20 kA m −1 . Aligning these nanowires parallel to the AMF increased SAR up to 2010 W g −1 Co 35 Fe 65 . Next, Co 35 Fe 65 nanowires were used to nanowarm vitrified VS55, a common cryoprotective agent (CPA).Nanowarming rates up to 1000 °C min −1 (5 mg Co 35 Fe 65 per ml VS55) were achieved, which is 20× faster than the critical warming rate (50 °C min −1 ) for VS55 and other common CPAs. Human dermal fibroblast cells exposed to VS55, and Co 35 Fe 65 nanowire concentrations of 0, 1 and 2.5 mg Fe per ml all showed similar cell viability, indicating that the nanowires had minimal cytotoxicity. With the ability to provide rapid and uniform heating, ferromagnetic nanowires have excellent potential for nanowarming cryopreserved tissues. 
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  3. Abstract

    Focal therapies such as hyperthermia have been successfully used to treat solid localized tumors; however, they are not easily applied to cancers that may present in a disseminated form such as ovarian cancer. To address this need, iron oxide (IO) particles were incorporated into microporous poly(caprolactone) scaffolds previously shown to recruit disseminating cancer cells. Under an alternating magnetic field, IO‐loaded scaffolds exhibited heating and killed ID8 ovarian cancer cells in vitro. After implantation in the intraperitoneal cavity of mice, IO‐loaded scaffolds became infiltrated with tissue after 6–7 weeks, and infiltrated cells were successfully treated ex vivo. Finally, IO‐loaded scaffolds noninvasively killed infiltrated cells in vivo as evidenced by decreases in number of nuclei. These studies demonstrate the promising use of IO‐loaded scaffolds as a tool for noninvasive hyperthermia, which could be an innovative modality for treatment of disseminated cancers.

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  4. Purposes

    To develop and evaluate a boundary informed electrical properties tomography (BIEPT) technique for high‐resolution imaging of tumor electrical properties (EPs) heterogeneity on a rodent tumor xenograft model.


    Tumor EP distributions were inferred from a reference area external to the tumor, as well as internal EP spatial variations derived from a plurality of relative transmit B1measurements at 7T. Edge sparsity constraint was enforced to enhance numerical stability. Phantom experiments were performed to determine the imaging accuracy and sensitivity for structures of various EP values, as well as geometrical sizes down to 1.5 mm. Numerical simulation of a realistic rodent model was used to quantify the algorithm performance in the presence of noise. Eleven athymic rats with human breast cancer xenograft were imaged in vivo, and representative pathological samples were acquired for comparison.


    Reconstructed EPs of the phantoms correspond well to the ground truth acquired from dielectric probe measurements, with the smallest structure reliably detectable being 3 mm. EPs heterogeneity inside a tumor is successfully retrieved in both simulated and experimental cases. In vivo tumor imaging results demonstrate similar local features and spatial patterns to anatomical MRI and pathological slides. The imaged conductivity of necrotic tissue is higher than that of viable tissues, which agrees with our expectation.


    BIEPT enables robust detection of tumor EPs heterogeneity with high accuracy and sensitivity to small structures. The retrieved quantitative EPs reflect tumor pathological features (e.g., necrosis). These results provide strong rationale to further expand BIEPT studies toward pathological conditions where EPs may yield valuable, non‐invasive biomarkers.

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