John C Bischof

University of Minnesota Twin Cities | UMN · Department of Mechanical Engineering

Coral reefs are threatened by anthropogenic climate change, which causes ocean acidification and warming that can result in coral death and the loss of genetic diversity on reefs around the world. Global efforts to secure the genetics of threatened populations using cryopreservation and biobanking are underway but are limited to coral sperm and lar...

Banking cryopreserved organs could transform transplantation into a planned procedure that more equitably reaches patients regardless of geographical and time constraints. Previous organ cryopreservation attempts have failed primarily due to ice formation, but a promising alternative is vitrification, or the rapid cooling of organs to a stable, ice...

Temperature in the body and the tumor reflects physiological and pathological conditions. A reliable, contactless, and simplistic measurement system can be used for long-term monitoring of disease progression and therapy response. In this study, miniaturized battery-free wireless chips implanted into growing tumors on small animals were used to cap...

Microinjection is a widely used technique for transgenesis, mutagenesis, cell labeling, cryopreservation, and in vitro fertilization in multiple single and multicellular organisms. Microinjection requires specialized skills acquired for each target organism and involves rate limiting and labor-intensive preparatory steps. Here we constructed a mach...

Climate change is causing ocean acidification and warming, resulting in mass bleaching and death of corals globally. Cryopreservation and biobanking to secure the genetics of threatened populations is currently limited to coral sperm and larvae, which are only available during brief annual spawning events and are impacted by ocean warming, so there...

When exposed to an external electric field, lipid bilayer membranes are subject to increased permeability through the generation of pores. Combining this phenomenon, known as electroporation, with liposomal drug delivery offers the added benefit of on-demand release of the liposomal cargo. In previous studies, the maximum percent drug release when...

The molecular weight, purity, and functionalization of polyethylene glycols are often characterized by 1H NMR spectroscopy. Oft-forgotten, the typical 1H NMR pulse sequence is not 13C decoupled. Hence, for large polymers, the 13C coupled 1H peaks arising from the repeating units have integrations comparable to that of the 1H of the terminal groups....

Cryopreservation by vitrification to achieve an "ice free" glassy state is an effective technique for preserving biomaterials including cells, tissues, and potentially even whole organs. The major challenges in cooling to and rewarming from a vitrified state remain ice crystallization and cracking/fracture. Ice crystallization can be inhibited by t...

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...

Cryosurgery is a minimally invasive approach to the treatment of focal prostate cancer (PCa). A major complication is the cryoinjury to the cavernous nerve in the neurovascular bundle (NVB). This nerve cryoinjury halts conduction of action potentials (APs) and can eventually result in erectile dysfunction and therefore diminished quality of life fo...

Deep-seated tumors of the liver, brain, and other organ systems often recur after initial surgical, chemotherapeutic, radiation, or focal treatments. Repeating these treatments is often invasive and traumatic. We propose an iron oxide nanoparticle (IONP)-enhanced precipitating hydrophobic injectable liquid (PHIL, MicroVention inc.) embolic as a loc...

Titanium nitride (TiN) is presented as an alternative plasmonic nanomaterial to the commonly used gold (Au) for its potential use in laser rewarming of cryopreserved biomaterials. The rewarming of vitrified, glass like state, cryopreserved biomaterials is a delicate process as potential ice formation leads to mechanical stress and cracking on a mac...

Magnetic nanowires (MNWs) can have their moments reversed via several mechanisms that are controlled using the composition, length, diameter, and density of nanowires in arrays as-synthesized or as individual nanoparticles in assays or gels. This tailoring of magnetic reversal leads to unique properties that can be used as a signature for reading o...

For highly sensitive point-of-care (POC) diagnostics, we explored the limit of thermal contrast amplification (TCA) reading of gold nanoparticles (GNPs/mm²) at test regions in immunoassays. More specifically, we built and compared fast (minute scale) and ultrafast (seconds scale) TCA setups using continuous-wave (CW) and ms pulsed lasers, respectiv...

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 st...

New preservation technologies may allow for organ banking similar to blood and biomaterial banking approaches.

Pancreatic islet transplantation can cure diabetes but requires accessible, high-quality islets in sufficient quantities. Cryopreservation could solve islet supply chain challenges by enabling quality-controlled banking and pooling of donor islets. Unfortunately, cryopreservation has not succeeded in this objective, as it must simultaneously provid...

DP6, VS55 and M22 are the most commonly used cryoprotective agent (CPA) cocktails for vitrification experiments in tissues and organs. However, complete phase diagrams for the three CPAs are often unavailable or incomplete (only available for full strength CPAs) thereby hampering optimization of vitrification and rewarming procedures. In this paper...

Focal therapies, including cryosurgery, thermal ablation and irreversible electroporation (IRE) have been widely used in the treatment of cancer and other diseases, aimed at exposing cancer cells to extreme physical conditions leading to cell death. Focal ablation outcomes have been extensively studied in small animal preclinical models, such as mi...

The cryopreservation of gametes and tissues is one of the most efficient tools for managing both large and small collections of valuable genetic resources. Cryopreservation minimizes the expenses associated with animal and facility maintenance, such as personnel, water, power, and space. It extends the time that offspring can be produced from indiv...

The SARS-CoV-2 global pandemic created an unprecedented need for rapid, sensitive, and inexpensive point-of-care (POC) diagnostic tests to treat and control the disease. Many POC SARS-CoV-2 lateral flow immunoassays (LFAs) have been developed and/or commercialized, but with only limited sensitivity (μM–fM). We created an advanced LFA based on gold...

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 computation means, while focusing on the human heart and the rat heart models....

This paper describes the extension of the classic Avrami equation to nonisothermal systems with arbitrary temperature time history and arbitrary initial distributions of transformed phase. We start by showing that though examination of phase change in Fourier space, we can decouple nucleation rate, growth rate, and transformed fraction, leading to...

Microinjection is a widely used technique employed by biologists with applications in transgenesis, cryopreservation, mutagenesis, labeling/dye injection and in-vitro fertilization. However, microinjection is an extremely laborious manual procedure, which makes it a critical bottleneck in the field and thus ripe for automation. Here, we present a c...

Cryoprotective agents (CPAs) are routinely used to vitrify, attain an amorphous glass state void of crystallization, and thereby cryopreserve biomaterials. Two vital characteristics of a CPA loaded system are the critical cooling and warming rates (CCR and CWR), the temperature rates needed to achieve and return from a vitrified state respectively....

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 techn...

Memory CD8+ T cells populate non-lymphoid tissues (NLTs) following pathogen infection, but little is known about the establishment of endogenous tumor-specific tissue-resident memory T cells (TRM) during cancer immunotherapy. Using a transplantable mouse model of prostate carcinoma, here we report that tumor challenge leads to expansion of naïve ne...

The development of a widely adopted cryopreservation method remains a major challenge in Drosophila research. Here we report a robust and easily implemented cryopreservation protocol of Drosophila melanogaster embryos. We present innovations for embryo permeabilization, cryoprotectant agent loading, and rewarming. We show that the protocol is broad...

Influenza poses a serious health threat and creates an economic burden for people around the world. The accurate diagnosis of influenza is critical to the timely clinical treatment of patients and the control of outbreaks to protect public health. Commercially available rapid influenza diagnostic tests (RIDTs) that are operated by visual readout ar...

Laser heating of gold nanospheres (GNS) is increasingly prevalent in biomedical applications due to tunable optical properties that determine heating efficiency. Although many geometric parameters (i.e. size, morphology) can affect optical properties of individual GNS and their heating, no specific studies of how GNS aggregation affects heating hav...

Lateral flow immunoassays: HIV detection A thermal contrast amplification variation of lateral flow immunoassays enables the ultrasensitive detection of the HIV p24 protein. The early detection of HIV relies on measuring p24 protein levels, as they appear in serum 7–10 days earlier than antibodies, another marker for HIV. Only small quantities of t...

Correction for 'Photothermal conversion of gold nanoparticles for uniform pulsed laser warming of vitrified biomaterials' by Yilin Liu et al., Nanoscale, 2020, 12, 12346-12356, DOI: 10.1039/D0NR01614D.

The objective of this study is to provide thermal conductivity data for CPA-based nanofluids for the benefit of the analyses of cryopreservation by vitrification. Thermal conductivity measurements were conducted using a hot-wire technique on an experimentation platform of the cryomacroscope, to correlate measurements with observed physical effects...

Cryopreserved tissues are increasingly needed in biomedical applications. However, successful cryopreservation is generally only reported for thin tissues (≤1 mm). This work presents several innovations to reduce cryoprotectant (CPA) toxicity and improve tissue cryopreservation, including 1) improved tissue warming rates through radiofrequency meta...

This study shows for the first time the ability to rewarm cryopreserved zebrafish embryos that grow into adult fish capable of breeding normally. The protocol employs a single injection of cryoprotective agents (CPAs) and gold nanorods (GNRs) into the yolk and immersion in a precooling bath to dehydrate the perivitelline space. Then embryos are enc...

Focal therapies such as hyperthermia have been successfully used to treat solid localized tumors; however, they are not easily applied to cancers which may present in a disseminated form such as ovarian cancer. To address this need, iron oxide particles were incorporated into microporous poly(caprolactone) scaffolds previously shown to recruit diss...

Pulsed laser (ms, 1064 nm) gold nanoparticle (GNP) heating has been used recently to achieve fast (> 10,000,000 °C min-1) warming of vitrified droplets using gold nanorods (GNRs) as photon-absorbers....

Treatment of atrial fibrillation by cryoablation of the pulmonary vein (PV) suffers from an inability to assess probe contact, tissue thickness, and freeze completion through the wall. Unfortunately, clinical imaging cannot be used for this purpose as these techniques have resolutions similar in scale (~ 1 - 2 mm) to PV thickness and therefore are...

Irreversible electroporation (IRE) is an emerging technology for non-thermal ablation of solid tumors. This study sought to integrate electrodes into microporous poly(caprolactone) (PCL) scaffolds previously shown to recruit metastasizing cancer cells in vivo in order to facilitate application of IRE to disseminating cancer cells. As the ideal para...

Cryopreservation technology allows long‐term banking of biological systems. However, a major challenge to cryopreserving organs remains in the rewarming of large volumes (>3 mL), where mechanical stress and ice formation during convective warming cause severe damage. Nanowarming technology presents a promising solution to rewarm organs rapidly and...

Purpose: Herein, we evaluate the use of MRI as a tool for assessing iron oxide nanoparticle (IONP) distribution within IONP perfused organs and vascularized composite allografts (VCAs) (i.e., hindlimbs) prepared for cryopreservation. Methods: Magnetic resonance imaging was performed on room-temperature organs and VCAs perfused with IONPs and wer...

The liver has unique regenerative properties that make it an ideal target for regenerative medicine applications. Hepatic systems are functional subunits of the liver and include hepatocytes, liver organoids, precision cut liver slices (PCLS), liver segments/lobes, and whole organs. Each has particular role in research, diagnostic, and therapeutic...

This work evaluates MRI relaxation and the specific absorption rate properties of iron oxide nanoparticles (IONPs) as a function of diameter (6-32 nm). We conclude that the ideal IONP diameter for image guided heating applications is dependent on the magnetic field strength of the MRI for the intended application. <br

For decades iron oxide nanoparticles (IONPs) have been exploited to treat anemia and to generate contrast for magnetic resonance imaging (MRI). More recently, in combination with magnetic fluid hyperthermia (MFH), IONPs have transitioned into the clinic as a cancer therapy. Review of the safety profile of IONPs as new clinical applications emerge i...

Ferromagnetic Co35Fe65, Fe, Co, and Ni nanowires have high saturation magnetizations (Ms) 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 usi...

Memory CD8+ T cells populate non-lymphoid tissues (NLT) and can protect against malignancies, but little is known about the establishment of tumor-specific tissue resident memory CD8+ T cells (TRM) by therapeutically initiated immune responses. We used a transplantable mouse model of prostate carcinoma and MHCI tetramers to track and quantify tumor...

Group A streptococcus causes significant health care costs and burdens. In the form of a mild infection, streptococcal pharyngitis is difficult to diagnose and manage while having the potential to progress to life-threatening invasive infections. The unsatisfactory performance of rapid diagnostic tests frequently requires follow-up high-sensitivity...

Focal thermal therapy (Heat), cryosurgery (Cryo) and irreversible electroporation (IRE) are increasingly used to treat cancer. However, local recurrence and systemic spread are persistent negative outcomes. Nevertheless, emerging work with immunotherapies (i.e., checkpoint blockade or dendritic cell (DC) vaccination) in concert with focal therapies...

Abstract Climate change has increased the incidence of coral bleaching events, resulting in the loss of ecosystem function and biodiversity on reefs around the world. As reef degradation accelerates, the need for innovative restoration tools has become acute. Despite past successes with ultra-low temperature storage of coral sperm to conserve genet...

Objective: Laser with 532-nm wavelength (GreenLightTM) is clinically approved to treat benign prostatic hyperplasia (BPH). However, low rate of tissue ablation and excessive thermal coagulation are shortcomings of this therapy. The goal of this study was to use a mathematical model to identify clinically viable laser settings that have the potentia...

Preventing ice formation during cryopreservation by vitrification has led to the successful storage and banking of numerous cellular and tissue-based biomaterials. In their breakthrough work, Peter Mazur’s group achieved over 90% survival by using a laser warming technique for 100 µm mice oocytes that were cooled in 0.1 µL droplets with 2.3M CPA an...

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. Methods Tumor EP distributions were inferred from a reference area external to the tumor, as well as internal EP spatial variations...

For applications of bioheat transfer such as thermal therapies and cryopreservation, the temperature excursions experienced by a biomaterial can be directly correlated to the injuries that may occur in the system. Thermal modeling is an important tool in order to predict this temperature history as it is not always possible to experimentally measur...

Cryopreservation represents one if not the only long-term option for tissue and perhaps future organ banking. In one particular approach, cryopreservation is achieved by completely avoiding ice formation (or crystallization) through a process called vitrification. This "ice-free" approach to tissue banking requires a combination of high-concentrati...

Arteries with 1-mm thick walls can be successfully vitrified by loading cryoprotective agents (CPAs) such as VS55 (8.4 M) or less concentrated DP6 (6 M) and cooling at or beyond their critical cooling rates of 2.5 and 40 °C/min, respectively. Successful warming from this vitrified state, however, can be challenging. For example, convective warming...

This chapter discusses the various parameters related to thermal analyses, phase change, enthalpy, and specific heat capacity, particularly in the cryogenic (<‐40 °C) and hyperthermic (>40 °C) regimes where water, protein, and lipid phase changes occur. It focuses on differential scanning calorimetry (DSC) at the microscale. The chapter introduces...

Atrial fibrillation affects millions of people in the US. Focal therapy is an attractive treatment for atrial fibrillation that avoids the debilitating effects of drugs for disease control. Perhaps the most widely used focal therapy for atrial fibrillation (AF) is heat-based radiofrequency (heating), although cryotherapy (cryo) is rapidly replacing...