Fibroblasts Accelerate Formation and Improve Reproducibility of 3D Cellular Structures Printed with Magnetic Assistance

Fibroblasts (mouse, NIH/3T3) are combined with MDA-MB-231 cells to accelerate the formation and improve the reproducibility of 3D cellular structures printed with magnetic assistance. Fibroblasts and MDA-MB-231 cells are cocultured to produce 12.5 : 87.5, 25 : 75, and 50 : 50 total population mixtures. These mixtures are suspended in a cell medium containing a paramagnetic salt, Gd-DTPA, which increases the magnetic susceptibility of the medium with respect to the cells. A 3D monotypic MDA-MB-231 cellular structure is printed within 24 hours with magnetic assistance, whereas it takes 48 hours to form a similar structure through gravitational settling alone. The maximum projected areas and circularities, and cellular ATP levels of the printed structures are measured for 336 hours. Increasing the relative amounts of the fibroblasts mixed with the MDA-MB-231 cells decreases the time taken to form the structures and improves their reproducibility. Structures produced through gravitational settling have larger maximum projected areas and cellular ATP, but are deemed less reproducible. The distribution of individual cell lines in the cocultured 3D cellular structures shows that printing with magnetic assistance yields 3D cellular structures that resemble in vivo tumors more closely than those formed through gravitational settling. The results validate our hypothesis that (1) fibroblasts act as a “glue” that supports the formation of 3D cellular structures, and (2) the structures are produced more rapidly and with greater reproducibility with magnetically assisted printing than through gravitational settling alone. Printing of 3D cellular structures with magnetic assistance has applications relevant to drug discovery, lab-on-chip devices, and tissue engineering.

Rapid Magnetic 3D Printing of Cellular Structures with MCF-7 Cell Inks

A contactless label-free method using a diamagnetophoretic ink to rapidly print three-dimensional (3D) scaffold-free multicellular structures is described. The inks consist of MCF-7 cells that are suspended in a culture medium to which a paramagnetic salt, diethylenetriaminepentaacetic acid gadolinium (III) dihydrogen salt hydrate (Gd-DTPA), is added. When a magnetic field is applied, the host fluid containing the paramagnetic salt is attracted towards regions of high magnetic field gradient, displacing the ink towards regions with a low gradient. Using this method, 3D structures are printed on ultra-low attachment (ULA) surfaces. On a tissue culture treated (TCT) surface, a 3D printed spheroid coexists with a two-dimensional (2D) cell monolayer, where the composite is termed as a 2.5D structure. The 3D structures can be magnetically printed within 6 hours in a medium containing 25 mM Gd-DTPA. The influence of the paramagnetic salt on MCF-7 cell viability, cell morphology, and ability of cells to adhere to each other to stabilize the printed structures on both ULA and TCT surfaces is investigated. Gene expressions of hypoxia-inducible factor 1-alpha (HIF1α) and vascular endothelial growth factor (VEGF) allow comparison of the relative stresses for the printed 3D and 2.5D cell geometries with those for 3D spheroids formed without magnetic assistance. This magnetic printing method can be potentially scaled to a higher throughput to rapidly print cells into 3D heterogeneous cell structures with variable geometries with repeatable dimensions for applications such as tissue engineering and tumour formation for drug discovery.

Rapid Magnetic 3D Printing of Cellular Structures with MCF-7 Cell Inks

A contactless label-free method using a diamagnetophoretic ink to rapidly print three-dimensional (3D) scaffold-free multicellular structures is described. The inks consist of MCF-7 cells that are suspended in a culture medium to which a paramagnetic salt, diethylenetriaminepentaacetic acid gadolinium (III) dihydrogen salt hydrate (Gd-DTPA), is added. When a magnetic field is applied, the host fluid containing the paramagnetic salt is attracted towards regions of high magnetic field gradient, displacing the ink towards regions with a low gradient. Using this method, 3D structures are printed on ultra-low attachment (ULA) surfaces. On a tissue culture treated (TCT) surface, a 3D printed spheroid coexists with a two-dimensional (2D) cell monolayer, where the composite is termed as a 2.5D structure. The 3D structures can be magnetically printed within 6 hours in a medium containing 25 mM Gd-DTPA. The influence of the paramagnetic salt on MCF-7 cell viability, cell morphology, and ability of cells to adhere to each other to stabilize the printed structures on both ULA and TCT surfaces is investigated. Gene expressions of hypoxia-inducible factor 1-alpha (HIF1α) and vascular endothelial growth factor (VEGF) allow comparison of the relative stresses for the printed 3D and 2.5D cell geometries with those for 3D spheroids formed without magnetic assistance. This magnetic printing method can be potentially scaled to a higher throughput to rapidly print cells into 3D heterogeneous cell structures with variable geometries with repeatable dimensions for applications such as tissue engineering and tumour formation for drug discovery.

The magnetocaloric effect of a paramagnetic salt from the point of view of Tsallis thermostatistics

In this work, we have studied the magnetocaloric effect (MCE) of a paramagnetic salt under the view of the Tsallis thermostatistics formalism. In order to model the paramagnetic salt we have used the simple two-level model. Within this model, it is possible to realize the role of the Tsallis parameter q for all thermodynamics variables calculated here, i.e. the internal energy, the specific heat, the entropy, and the magnetocaloric potential. The main result presented in this work is the relation between the total heat related to the MCE and the q-parameter of the Tsallis theory. There is a threshold value of q where, above this value, the total heat change is constant for all q while below this value, there is a quick decreasing.

Simple Systems

Even though the general framework of statistical mechanics is ultimately targeted at the description of macroscopic systems, it is illustrative to apply it first to some simple systems: a harmonic oscillator, a rotor, and a spin in a magnetic field. These applications serve to illustrate how a key function associated with the Gibbs state, the so-called partition function, is calculated in practice, how the entropy function is obtained via a Legendre transformation, and how such systems behave in the limits of high and low temperatures. After discussing these simple systems, this chapter considers a first example where multiple constituents are assembled into a macroscopic system: a basic model of a paramagnetic salt. It also investigates the size of energy fluctuations and how—in the case of the paramagnet—these fluctuations scale with the number of constituents.

PARAMAGNETIC MATERIALS AND PRACTICAL ALGORITHMIC COOLING FOR NMR QUANTUM COMPUTING

Algorithmic cooling is a method that uses novel data compression techniques and simple quantum computing devices to improve NMR spectroscopy, and to offer scalable NMR quantum computers. The algorithm recursively employs two steps. A reversible entropy compression of computation quantum-bits (qubits) of the system and an irreversible heat transfer from the system to the environment through a set of reset qubits that reach thermal relaxation rapidly. Is it possible to experimentally demonstrate algorithmic cooling using existing technology? To allow experimental algorithmic cooling, the thermalization time of the reset qubits must be much shorter than the thermalization time of the computation qubits. However, such high thermalization-times ratios have yet to be reported. We investigate here the effect of a paramagnetic salt on the thermalization-times ratio of computation qubits (carbons) and a reset qubit (hydrogen). We show that the thermalization-times ratio is improved by approximately three-fold. Based on this result, an experimental demonstration of algorithmic cooling by thermalization and magnetic ions has been performed by the authors and collaborators.