Zhenpeng Qin

Multisite Validation of Cryptococcal Antigen Lateral Flow Assay and Quantification by Laser Thermal Contrast

This assay is a major advance in the diagnosis of cryptococcal meningitis.

Significantly Improved Analytical Sensitivity of Lateral Flow Immunoassays by Using Thermal Contrast

The ability to rapidly identify diseases enables prompt treatment and improves outcomes. This has increased the development and use of rapid point-of-care diagnostic devices capable of biomolecular detection in both high-income and resource-limited settings.[1] Lateral flow assays (LFAs) are inexpensive, simple, portable, and robust,[2] making LFAs commonplace in medicine, agriculture, and over-the-counter personal use such as for pregnancy testing. Although the analytical performance of some LFAs are comparable to laboratory based methods,[1a] the sensitivity of most LFAs is in the mM to μM range,[2–3] which is many folds less sensitive than other molecular techniques such as enzyme-linked immunoassays (ELISA). As a consequence, LFAs are not particularly useful for detection early in a disease course when there is low level of antigen. Due to the increasing need for highly sensitive molecular diagnostics, researchers have focused on developing microfluidics,[1a, 1b] biobar codes,[1c, 1d] and enzyme-based immunoassay technologies[4] technologies to fulfill the need since these technologies have nM to pM detection sensitivity for protein analysis and can potentially be miniaturized as handheld point-of-care diagnostic devices.[1c] These emerging technologies are still early in development and are not yet field-ready.

Membrane-Targeting Approaches for Enhanced Cancer Cell Destruction with Irreversible Electroporation

Irreversible electroporation (IRE) is a promising technology to treat local malignant cancer using short, high-voltage electric pulses. Unfortunately, in vivo studies show that IRE suffers from an inability to destroy large volumes of cancer tissue without introduction of cytotoxic agents and/or increasing the applied electrical dose to dangerous levels. This research will address this limitation by leveraging membrane-targeting mechanisms that increase lethal membrane permeabilization. Methods that directly modify membrane properties or change the pulse delivery timing are proposed that do not rely on cytotoxic agents. This work shows that significant enhancement (67–75% more cell destruction in vitro and >100% treatment volume increase in vivo) can be achieved using membrane-targeting approaches for IRE cancer destruction. The methods introduced are surfactants (i.e., DMSO) and pulse timing which are low cost, non-toxic, and easy to be incorporated into existing clinical use. Moreover, when needed, these methods can also be combined with electrochemotherapy to further enhance IRE treatment efficacy.

Gold Nanorod Induced Warming of Embryos from the Cryogenic State Enhances Viability

Zebrafish embryos can attain a stable cryogenic state by microinjection of cryoprotectants followed by rapid cooling, but the massive size of the embryo has consistently led to failure during the convective warming process. Here we address this zebrafish cryopreservation problem by using gold nanorods (GNRs) to assist in the warming process. Specifically, we microinjected the cryoprotectant propylene glycol into zebrafish embryos along with GNRs, and the samples were cooled at a rate of 90 000 °C/min in liquid nitrogen. We demonstrated the ability to unfreeze the zebrafish rapidly (1.4 × 107 °C/min) by irradiating the sample with a 1064 nm laser pulse for 1 ms due to the excitation of GNRs. This rapid warming process led to the outrunning of ice formation, which can damage the embryos. The results from 14 trials (n = 223) demonstrated viable embryos with consistent structure at 1 h (31%) and continuing development at 3 h (17%) and movement at 24 h (10%) postwarming. This compares starkly with 0% viability, structure, or movement at all time points in convectively warmed controls (n = 50, p < 0.001, ANOVA). Our nanoparticle-based warming process could be applied to the storage of fish, and with proper modification, can potentially be used for other vertebrate embryos.

One Dimensional Experimental Setup to Study the Heating of Nanoparticle Laden Systems

Intensive efforts have been put into the use of gold nanoparticles (GNPs) for the enhancement of hyperthermia using laser in recent years since the groundbreaking work of Hirsh et al.(1) using gold nanoshells (GNS). Both in vitro (2), and in vivo (3) studies show promising results. For example, GNS, a special kind of GNP, are being manufactured and are in clinical trials (Nanospectra Bioscience, Inc). While the data is compelling, unfortunately the fundamentals of GNP heating are not entirely understood. For example, there are large discrepancies in the experimentally measured photothermal efficiency of GNPs (4, 5). Furthermore, lumped models of GNP heating in solution, by using small volume of GNP solution (4, 5), or stirring the solution (6), neglecting the variation of heat absorption throughout a system require improvement. In reality, the GNPs will attenuate the laser beam as it passes through the GNP host medium. GNPs at different locations will absorb different amount of laser energy and hence have different heat generation.Copyright

An in vitro study on adjuvant enhanced irreversible electroporation

Recently, irreversible electroporation (IRE) has emerged as a promising tumor ablation technique. IRE induces cell death by irreversibly compromising membrane integrity with a series of short, high voltage electrical pulses [1]. IRE offers many advantages over surgery and thermal ablations including that it 1) is fast and minimally invasive, 2) destroys the tumor while preserving adjacent connective tissues [2], and 3) can be delivered with negligible thermal injury [3]. Here we hypothesize that the thresholds necessary to successfully electroporate cancer cell membranes, and therefore more effectively destroy an entire tumor, can be dramatically improved by careful choice of 1) electroporation parameter, and 2) chemical adjuvants that specifically impact the cell membrane.Copyright

Thermal Analysis Measurement of Gold Nanoparticle Interactions With Cell and Biomaterial

The rapidly evolving field of nanomedicine focuses on the design and application of multi-functional nanoparticles for diagnosis and treatment of diseases especially cancer1. Many of these nanomaterials are designed to serve as drug delivery or image contrast agents, or even to generate heat for hyperthermia (i.e. treatment), of cancer. Heating examples include gold nanoparticles (GNPs) for photothermal therapy3, and superparamagnetic nanoparticles for magnetic fluid hyperthermia4.© 2012 ASME

Irreversible electroporation: An in vivo study within the dorsal skin fold chamber

Electroporation has been traditionally used to enhance molecular transport into cells (e.g. gene therapy) and through tissues (e.g. skin) by creating reversible pores with short electrical pulses [1]. Increasing the parameters (electrical field, pulse duration and number) can induce irreversible damage to the cells and tissue. Recently, irreversible electroporation (IRE) has been investigated as a new tumor ablation method [2]. The advantages of the IRE include the simple and fast procedure (train of μs pulses), sharp demarcation between treated and untreated regions, destruction of tumor cells while preserving the connective tissue, and minimal effect of immune response on treatment efficacy [3]. The unique interaction of electrical field with heterogeneous structures prevents damage to nerves, blood vessels and ducts [4]. IRE has been claimed to produce negligible thermal injury and protein denaturation typical to thermal ablation [5]. However, how each electroporation parameter in IRE affects tumor destruction and the possibility of heating remains to be studied in tumors vivo.Copyright