Cryopreserved leukapheresis material can be transferred from controlled rate freezers to ultracold storage at warmer temperatures without affecting downstream CAR-T cell culture performance and in-vitro functionality.

Chimeric antigen receptor (CAR) T-cell therapies are increasingly adopted as a commercially available treatment for hematologic and solid tumor cancers. As CAR-T therapies reach more patients globally, the cryopreservation and banking of patients' leukapheresis materials is becoming imperative to accommodate intra/inter-national shipping logistical delays and provide greater manufacturing flexibility. This study aims to determine the optimal temperature range for transferring cryopreserved leukapheresis materials from two distinct types of controlled rate freezing systems, Liquid Nitrogen (LN2)-based and LN2-free Conduction Cooling-based, to the ultracold LN2 storage freezer (≤-135 °C), and its impact on CAR T-cell production and functionality. Presented findings demonstrate that there is no significant influence on CAR T-cell expansion, differentiation, or downstream in-vitro function when employing a transfer temperature range spanning from -30 °C to -80 °C for the LN2-based controlled rate freezers as well as for conduction cooling controlled rate freezers. Notably, CAR T-cells generated from cryopreserved leukapheresis materials using the conduction cooling controlled rate freezer exhibited suboptimal performance in certain donors at transfer temperatures lower than -60 °C, possibly due to the reduced cooling rate of lower than 1 °C/min and extended dwelling time needed to reach the final temperatures within these systems. This cohort of data suggests that there is a low risk to transfer cryopreserved leukapheresis materials at higher temperatures (between -30 °C and -60 °C) with good functional recovery using either controlled cooling system, and the cryopreserved materials are suitable to use as the starting material for autologous CAR T-cell therapies.

First-Cut Design of a Benchtop Cryogen-Free 23.5-T/25-mm Magnet for 1-GHz Microcoil NMR.

As a preliminary work, we have completed a 12.5-mm-cold-bore high-temperature superconducting (HTS) REBCO magnet prototype and successfully operated it up to 25 T at 10 K cooled by a cryocooler only, without liquid helium. In this paper we present the first-cut design of a cryogen-free all-REBCO 23.5-T/25-mm-warm-bore magnet having a high homogeneity of <0.1 ppm over a 1-cm diameter of spherical volume for a benchtop 1-GHz microcoil NMR spectroscopy. We also investigate a shielding design to reduce a 5-gauss fringe field radius to ≤1.5 m. This benchtop magnet will incorporate all the innovative design and operation concepts validated by the prototype magnet: 1) all-HTS composition and operation at above 4.2 K; 2) no-insulation winding technique with an extra shunting that makes this high-field REBCO magnet compact, mechanically robust, and self-protecting; 3) a single coil formation that leads, compared with the traditional multi-nested high-field NMR magnet, to simpler and more affordable manufacturing processes; 4) operational temperature-controlled screening-current reduction method which reduces peak stresses within the REBCO coil and field errors; and 5) cryogenic design for conduction-cooling operation.

Magnetic, Mechanical and Thermal Modeling of Superconducting, Whole-body, Actively Shielded, 3 T MRI Magnets Wound Using MgB2 Strands for Liquid Cryogen Free Operation.

we present magnetic, mechanical and thermal modeling results for a 3 Tesla actively shielded whole body MRI (Magnetic Resonance Imaging) magnet consisting of coils with a square cross section of their windings. The magnet design was a segmented coil type optimized to minimize conductor length while hitting the standard field quality and DSV (Diameter of Spherical Volume) specifications as well as a standard, compact size 3 T system. It had an overall magnet length and conductor length which can lead to conduction cooled designs comparable to NbTi helium bath cooled 3 T MRI magnets. The design had a magnetic field homogeneity better than 10 ppm (part-per-million) within a DSV (Diameter of Spherical Volume) of 48 cm and the total magnet winding length of 1.37 m. A new class of MgB2 strand especially designed for MRI applications was considered as a possible candidate for winding such magnets. This work represents the first magnetic, mechanical and thermal design for a whole-body 3 T MgB2 short (1.37 m length) MRI magnet based on the performance parameters of existing MgB2 wire. 3 Tesla MRI magnet can operate at 20 K at 67 % of its critical current.

Finite element analysis of the temperature distribution within a Conduction-Cooled, MgB2-based MRI superconducting coil segment.

Superconducting magnets used for Magnetic Resonance Imaging (MRI) scanners need to keep temperature gradients minimized in order to retain thermal and operating current margin. We have used 3D finite element analysis (FEA) simulation in COMSOL Multiphysics software that includes both conductive heat transfer and radiative heating to calculate the temperature distribution both along the winding direction and across the cross-section of an MRI segment coil at its equilibrium operating temperature. We have also modelled the evolution of the thermal properties during cool-down from ambient temperature. The heat capacity and thermal conductivity of the magnet winding were computed for use within this simulation. The heat capacity as a function of temperature was calculated using a rule of mixtures. This procedure was also used for the thermal conductivity along the direction of the wire. However, the thermal conductivity within the composite cross section (x- and y-directions) was computed using a 2D FEA model. Based on this, a time-dependent, 3D coil model was built to calculate the coil temperature throughout the winding during cool-down in our test cryostat system. The model included a heat leak component to the coil current contacts via conduction through the current leads as well as a radiative component from the surfaces of the cryostat. A key result was that a maximum coil ΔTmax = 5.1 K (=maximum temperature within the winding -minimum temperature in the winding) was seen and a coil Ic margin of 12.75 A was predicted at steady state, with our first current lead design. A second set of more optimized current leads significantly lowered the ΔTmax within the coil at the steady state. The coil Ic margin has been analyzed for different current lead designs.

Conduction Cooling and Plasmonic Heating Dramatically Increase Droplet Vitrification Volumes for Cell Cryopreservation.

Droplet vitrification has emerged as a promising ice-free cryopreservation approach to provide a supply chain for off-the-shelf cell products in cell therapy and regenerative medicine applications. Translation of this approach requires the use of low concentration (i.e., low toxicity) permeable cryoprotectant agents (CPA) and high post cryopreservation viability (>90%), thereby demanding fast cooling and warming rates. Unfortunately, with traditional approaches using convective heat transfer, the droplet volumes that can be successfully vitrified and rewarmed are impractically small (i.e., 180 picoliter) for <2.5 m permeable CPA. Herein, a novel approach to achieve 90-95% viability in micro-liter size droplets with 2 m permeable CPA, is presented. Droplets with plasmonic gold nanorods (GNRs) are printed onto a cryogenic copper substrate for improved cooling rates via conduction, while plasmonic laser heating yields >400-fold improvement in warming rates over traditional convective approach. High viability cryopreservation is then demonstrated in a model cell line (human dermal fibroblasts) and an important regenerative medicine cell line (human umbilical cord blood stem cells). This approach opens a new paradigm for cryopreservation and rewarming of dramatically larger volume droplets at lower CPA concentration for cell therapy and other regenerative medicine applications.

A Tabletop Persistent-Mode, Liquid Helium-Free 1.5-T MgB2 "Finger" MRI Magnet: Construction and Operation of a Prototype Magnet.

This paper presents results of construction and operation of a persistent-mode, liquid-helium-free, small-scale prototype magnet for the development of a tabletop 1.5-T "finger" MRI system for osteoporosis screening. The prototype magnet, composed of 2 MgB2 coils, one superconducting joint, and a persistent-current switch (PCS) built from a portion of one coil, was wound with a one continuous ~80-m long unreacted and monofilament MgB2 wire and then reacted. The test magnet was charged successfully and generated the estimated target field of 1.75 T at 5 K with the proposed PCS operation. During initial persistent-mode, the field was slightly decayed due to the index dissipation of the joint; thereafter it sustained the persistent field of 1.7 T for 35 h. The test results validated the joint resistance of < 1.2 × 10-11 as well as the proposed approach involving the PCS coil circuit model.

Quench, Normal Zone Propagation Velocity, and the Development of an Active Protection Scheme for a Conduction Cooled, R&W, MgB2 MRI Coil Segment.

The development of coils that can survive a quench is crucial for demonstrating the viability of MgB2-based main magnet coils used in MRI systems. Here we have studied the performance and quench properties of a large (outer diameter: 901 mm; winding pack: 44 mm thick × 50.6 mm high) conduction-cooled, react-and-wind (R&W), MgB2 superconducting coil. Minimum quench energy (MQE) values were measured at several coil operating currents (I op ), and distinguished from the minimum energy needed to generate a normal zone (MGE). During these measurements, normal zone propagation velocities (NZPV) were also determined using multiple voltage taps placed around the heater zone. The conduction cooled coil obtained a critical current (I c ) of 186 A at 15 K. As the operating currents (I op ) varied from 80 A to 175 A, MQE ranged from 152 J to 10 J, and NZPV increased from 1.3 to 5.5 cm/s. Two kinds of heater were involved in this study: (1) a localized heater ("test heater") used to initiate the quench, and (2) a larger "protection heater" used to protect the coil by distributing the normal zone after a quench was detected. The protection heater was placed on the outside surface of the coil winding. The test heater was also placed on the outside surface of the coil at a small opening made in the protection heater. As part of this work, we also developed and tested an active protection scheme for the coil. Such active protection schemes are of great interest for MgB2-based MRIs because they permit exploitation of the relatively large MQE values of MgB2 to enable the use of higher J e values which in turn lead to competitive MgB2 MRI designs. Finally, the ability to use a quench detection voltage to fire a protection heater as part of an active protection scheme was also demonstrated.

A REBCO Persistent-Current Switch, Immersed in Solid Nitrogen, Operating at Temperatures near 10 K.

We present design and test results for a thermally-activated persistent-current switch (PCS) applied to a double pancake (DP) coil (151 mm ID, 172 mm OD), wound, using the no-insulation (NI) technique, from a 120-m long, 76-µm thick, 6-mm wide REBCO tape. For the experiments reported in this paper, the NI DP assembly was immersed in a volume of solid nitrogen (SN2), cooled to a base temperature of 10 K by conduction to a two-stage cryocooler, and energized at up to 630 A. The DP assembly operated in quasi-persistent mode, with the conductor tails soldered together to form a close-out joint with resistance below 6 nΩ. The measurements confirm PCS activation at heating powers below our 1-W design target, and a field decay time constant in excess of 900 h (i.e 0.1% h-1 field decay rate), limited by the finite resistance of the close-out joint.

Demonstration of a Conduction Cooled React and Wind MgB2 Coil Segment for MRI Applications.

This study is a contribution to the development of technology for an MgB2-based, cryogen-free, superconducting magnet for an MRI system. Specifically, we aim to demonstrate that a react and wind coil can be made using high performance in-situ route MgB2 conductor, and that the conductor could be operated in conduction mode with low levels of temperature gradient. In this work, an MgB2 conductor was used for the winding of a sub-size, MRI-like coil segment. The MgB2 coil was wound on a 457 mm ID 101 OFE copper former using a react-and-wind approach. The total length of conductor used was 330 m. The coil was epoxy impregnated and then instrumented for low temperature testing. After the initial cool down (conduction cooling) the coil Ic was measured as a function of temperature (15-30 K), and an Ic of 200 A at 15 K was measured.

Development of a 3 T-250 mm Bore MgB2 Magnet System.

The authors had reported components' development of 3 T-250 mm bore MgB2 magnet system. Pre-reacted MgB2 tape wire with copper lamination had n-value related problem due to raw Boron particle size inequality, but it had been corrected. Long MgB2 wires over 3 km had been supplied. All six component coils were made with a wet winding procedure. They were tested individually with the same cooling scheme of conduction cooling as the actual magnet assembly. Though all coils could be ramped to some extent, some coils showed fairly large remnant voltage. Since the voltage distribution over the coil was not even, the uniformity along the wire length may not be good enough. The stability of the coil was verified by its no training performance even with fast ramping. The magnet assembly and its test with conduction cooling were planned. I c of the superconducting joint with this pre-reacted wire was doubled during past one year's development.