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Creators/Authors contains: "Gao, Zhe"

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  1. Free, publicly-accessible full text available January 1, 2026
  2. New preservation technologies may allow for organ banking similar to blood and biomaterial banking approaches. Using cryoprotective agents (CPAs), aqueous solutions with organic components such as DMSO, propylene glycol, and added salts and sugars, organs can be used to vitrify and store organs at −140 °C. When needed, these organs can be rewarmed in a rapid and uniform manner if CPAs are supplemented with iron oxide nanoparticles (IONPs) in an applied radiofrequency field. Speed and uniformity of warming are both IONP concentration and CPA suspension dependent. Here we present a coating method of small molecule phosphonate linker (PLink) and biocompatible polymer ( i.e. polyethylene glycol PEG) that tunes stability and increases the maximum allowable concentration of IONPs in CPA suspension. PLink contains a phosphonate 'anchor' for high irreversible binding to iron oxide and a carboxylic acid 'handle' for ligand attachment. PLink-PEG removes and replaces the initial coating layer of commercially available IONPs (EMG1200 (hydrophobic) and EMG308 (hydrophilic) Ferrotec, Inc., increasing colloidal stability and decreasing aggregation in both water and CPAs, (verified with dynamic light scattering) from minutes (uncoated) to up to 6 days. Heating properties of EMG1200, specific absorption rate (SAR), measured using an applied field of 360 kHz and 20 kA m −1 , increased from 20 to 180 W per g Fe with increasing PLink-PEG5000. PEG replacing the initially hydrophobic coating decreased aggregation in water and CPA, consistent with earlier studies on heating performance. Furthermore, although the size is minimized at 0.20 mol PEG per g Fe, heating is not maximized until concentrations above 0.43 mol PEG per g Fe on EMG1200. SAR on hydrophilic EMG308 was preserved at 400 W per g Fe regardless of the amount of PLink added to the core. Herein concentrations of IONP in VS55 (common CPA) significantly above our previous capabilities, sIONP at 10 mg Fe per mL, was reached, 25 mg Fe per mL of 308-PEG5000 and 60 mg Fe per mL of 1200-PEG5000, approaching stock EMG308 in water, 60 mg Fe per mL. Furthermore, at these concentrations cryopreserved Human dermal fibroblast cells were successfully nanowarmed (at applied fields described above), with higher viability as compared to convective rewarming in a water bath and heating rate close to 200 °C min −1 , 2.5 times faster than our current system. Using PLink as the coating method allowed for higher concentrations of IONPs to be successfully suspended in CPA without affecting the heating ability. Additionally, the model ligand, PEG, allowed for increased stability over time in nanowarming experiments. 
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  3. Heart valve cryopreservation was employed as a model for the development of complex tissue preservation methods based upon vitrification and nanowarming. Porcine heart valves were loaded with cryoprotectant formulations step wise and vitrified in 1–30 mL cryoprotectant formulations ± Fe nanoparticles ± 0.6 M disaccharides, cooled to −100 °C, and stored at −135 °C. Nanowarming was performed in a single ~100 s step by inductive heating within a magnetic field. Controls consisted of fresh and convection-warmed vitrified heart valves without nanoparticles. After washing, cell viability was assessed by metabolic assay. The nanowarmed leaflets were well preserved, with a viability similar to untreated fresh leaflets over several days post warming. The convection-warmed leaflet viability was not significantly different than that of the nanowarmed leaflets immediately after rewarming; however, a significantly higher nanowarmed leaflet viability (p < 0.05) was observed over time in vitro. In contrast, the associated artery and fibrous cardiac muscle were at best 75% viable, and viability decreased over time in vitro. Supplementation of lower concentration cryoprotectant formulations with disaccharides promoted viability. Thicker tissues benefited from longer-duration cryoprotectant loading steps. The best outcomes included a post-warming incubation step with α-tocopherol and an apoptosis inhibitor, Q-VD-OPH. This work demonstrates progress in the control of ice formation and cytotoxicity hurdles for the preservation of complex tissues. 
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  4. Abstract This study explores thermal design aspects of nanowarming-assisted recovery of the heart from indefinite cryogenic storage, where nanowarming is the volumetric heating effect of ferromagnetic nanoparticles excited by a radio frequency electromagnet field. This study uses computational means while focusing on the human heart and the rat heart models. The underlying nanoparticle loading characteristics are adapted from a recent, proof-of-concept experimental study. While uniformly distributed nanoparticles can lead to uniform rewarming, and thereby minimize adverse effects associated with ice crystallization and thermomechanical stress, the combined effects of heart anatomy and nanoparticle loading limitations present practical challenges which this study comes to address. Results of this study demonstrate that under such combined effects, nonuniform nanoparticles warming may lead to a subcritical rewarming rate in some parts of the domain, excessive heating in others, and increased exposure potential to cryoprotective agents (CPAs) toxicity. Nonetheless, the results of this study also demonstrate that computerized planning of the cryopreservation protocol and container design can help mitigate the associated adverse effects, with examples relating to adjusting the CPA and/or nanoparticle concentration, and selecting heart container geometry, and size. In conclusion, nanowarming may provide superior conditions for organ recovery from cryogenic storage under carefully selected conditions, which comes with an elevated complexity of protocol planning and optimization. 
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  5. Studies on human mobility have a long history with increasingly strong interdisciplinary connections across social science, environmental science, information and technology, computer science, engineering, and health science. However, what is lacking in the current research is a synthesis of the studies to identify the evolutional pathways and future research directions. To address this gap, we conduct a systematic review of human mobility-related studies published from 1990 to 2020. Drawing on the selected publications retrieved from the Web of Science, we provide a bibliometric analysis and network visualisation using CiteSpace and VOSviewer on the number of publications and year published, authors and their countries and afflictions, citations, topics, abstracts, keywords, and journals. Our findings show that human mobility-related studies have become increasingly interdisciplinary and multi-dimensional, which have been strengthened by the use of the so-called ‘big data’ from multiple sources, the development of computer technologies, the innovation of modelling approaches, and the novel applications in various areas. Based on our synthesis of the work by top cited authors we identify four directions for future research relating to data sources, modelling methods, applications, and technologies. We advocate for more in-depth research on human mobility using multi-source big data, improving modelling methods and integrating advanced technologies including artificial intelligence, and machine and deep learning to address real-world problems and contribute to social good. 
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  6. 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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  7. Abstract Metal film over nanosphere (FON) substrates are a mainstay of surface‐enhanced Raman scattering (SERS) measurements because they are inexpensive to fabricate, have predictable enhancement factors, and are relatively robust. This work includes a systematic investigation of how the three major FON fabrication parameters—nanosphere size, deposited metal thickness, and metal choice—impact the resulting localized surface plasmon resonance (LSPR). With these three parameters, it is quite simple to fabricate FONs with an optimal LSPR for SERS experiments with various excitation wavelengths. Some SERS experiments require that the substrates be incubated in organic solvents that have the potential to damage the substrate; as such, this work also explores how solvent incubation impacts the physical and optical properties of the FON substrate. Although no significant increase in physical damage is obvious, the LSPR does shift significantly. Finally, these optimized FONs were employed for the sensing of an important allergen, soybean agglutinin. The FONs were modified with a glycopolymer that has affinity for soybean agglutinin and clear Raman bands demonstrate detection of 10 μg/ml soybean agglutinin. Overall, this work serves the dual purpose of both sharing critical details about FON design and demonstrating detection of an important lectin analyte. 
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  8. Abstract Vitrification can dramatically increase the storage of viable biomaterials in the cryogenic state for years. Unfortunately, vitrified systems ≥3 mL like large tissues and organs, cannot currently be rewarmed sufficiently rapidly or uniformly by convective approaches to avoid ice crystallization or cracking failures. A new volumetric rewarming technology entitled “nanowarming” addresses this problem by using radiofrequency excited iron oxide nanoparticles to rewarm vitrified systems rapidly and uniformly. Here, for the first time, successful recovery of a rat kidney from the vitrified state using nanowarming, is shown. First, kidneys are perfused via the renal artery with a cryoprotective cocktail (CPA) and silica‐coated iron oxide nanoparticles (sIONPs). After cooling at −40 °C min−1in a controlled rate freezer, microcomputed tomography (µCT) imaging is used to verify the distribution of the sIONPs and the vitrified state of the kidneys. By applying a radiofrequency field to excite the distributed sIONPs, the vitrified kidneys are nanowarmed at a mean rate of 63.7 °C min−1. Experiments and modeling show the avoidance of both ice crystallization and cracking during these processes. Histology and confocal imaging show that nanowarmed kidneys are dramatically better than convective rewarming controls. This work suggests that kidney nanowarming holds tremendous promise for transplantation. 
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