An immortalised adult human erythoid line facilitates sustainable and scalable generation of functional red cells

CSS450 shown above

Medical advancements in the last few decades have seen the average human life expectancy notably increase. However, despite improved medical techniques and procedures, the demand for blood is ever increasing. Donated blood is in short supply and has a limited shelf life while current in-vitro methods of culturing do not provide a sustainable supply suitable for clinical needs. 

Trakarnsanga et al., discovered a method of creating an immortal red blood cell (RBC) supply. Through testing these RBCs have been shown to be molecularly and functionally similar to in vitro cultured RBCs. 

Stem cells are cells which are capable of proliferating into many - and sometimes all - types of cells. Previous in-vitro methods of culturing RBCs used the differentiating abilities of stem cells to produce RBCs from adult peripheral blood or umbilical cord blood stem cells. However, these RBCs have limited proliferation capacity and cells derived from cord blood often show fetal phenotypes. 

Trakarnsanga et al., produced the BEL-A (Bristol Erythroid Line Adult) line which was created through transducing early erythroid cells grown from adult bone marrow stem cells with a plasmid construct. Environmental control maintained these erythroid cells in an indefinitely proliferative state. The cultured cells could then be induced to complete maturation through removal of the inducing factor. The bloodgroup of the cultured RBC matched that of the cell donor while the protein expression profiles of these cells were found to be similar to in-vitro cultured RBCs. 

RBCs must be able to change shape under the stress of mechanical forces without rupturing. Testing this property in the BEL-A line is vital for clinical use. The group used the CSS450 shear stage, Imaging Station and Linkam imaging and control software to test the deformability of the cultured cells. The BEL-A line bound oxygen and had deformability indexes comparable to normal RBCs. 

Transplantation of the BEL-A line into a murine host also proved successful with no difference in survival rate between these mice and mice transplanted with donor RBCs. 

The group have created an immortal RBC line which through testing, matches in-vitro and normal RBCs in all categories tested. The discovery could provide a reliable and suitable blood source for those with rare blood groups and those requiring regular transfusions. Although more work will need to be done before clinical use, the ability to create RBCs through an immortal line could help alleviate the pressure of securing blood donors for patients and could prove life-changing for many.  

Read the full paper here
 

Research into the different constituents of Lithium Ion Batteries using Linkam’s LTS120.

Lithium ion batteries (LIBs) are heavily used in the portable electronics industry due to their low weight and high energy output. Although they are incredibly popular, improvements can be made in terms of capacity and replacing the volatile and flammable organic solvents within the batteries. 

Researchers at the Warsaw University of Technology researched the different constituents of Lithium Ion Batteries (LIBs) to increase the conductivity and capacity of the ionic liquid-lithium salt binary system. This was done by introducing lithium salt as a Li+ cation glyme solvent. By using Linkam’s LTS120 system with a Raman spectrometer they could study phase transitions and salt dissociation, giving a better understanding of the conducting mechanism. 

Due to their great conductivity, Ionic liquids (ILs) could be a potential replacement for the dangerous solvents in LIBs. However, there are several issues with their incorporation. Firstly, ILs are produced on a small scale so they are very expensive. Secondly, their high melting points, poor compatibility with electrodes and other electrochemical properties make them less ideal as lithium conducting electrolytes. 

The research group created a new family of ILs to try and improve on the disadvantages of the classic ILs. The ionic salts were mixed with LiTDI salt to create a XMIm+TDI- LiTDI system. This formed a chain shaped [Li(TDI)2]nn- and XMIm+, but this system was found to be a poor conductor of lithium ions. 

Studies from another group found the solvent glyme, when mixed with LiTDI salt, creates a solvated Li(glyme)+ cation and Li polyanion system which is great for ionic conductivity as well as Li cation transference. Both qualities were desired in the Warsaw group’s BMIm+TDI- LiTDI system. 

Karpierz, E. et al. thus incorporated the solvent glyme into their system. Their ternary mixture consisted of an aggregated system of [Li(glyme)]+ cations and [Li(TDI)2]NN- anions dissolved in the ionic liquid BMIm+TDI-. They discovered the order and method of mixing affected the electrochemical properties of their system. They found that by mixing the LiTDI with the glyme first for at least six hours followed by the addition of the ionic liquid, it produces the system with the greatest conductivity.

The group have found a novel method of improving the ionic liquid-lithium salt binary system, which could have great potential application in lithium ion batteries.  

Find out more here

Karpierz, E. et al. Ternary mixtures of ionic liquids for better salt solubility, conductivity and cation transference number improvement. Sci. Rep. 6, 35587; doi: 10.1038/srep35587 (2016).
 

Investigating a chaotic self-oscillating sunlight-driven polymer actuator using Linkam’s THMS600

THMS600 shown above

In nature, it is common to find self-oscillating systems. These systems are either self-regulated or respond to external stimuli. Recreating this process synthetically is of great interest to scientists yet currently, there are only several attempted examples, all chemically driven and within non-dry systems. However, a light driven non-invasive system which would work in dry environments would prove to be much more useful. 

Self-oscillating actuators would have incredible application in self-cleaning devices and even as a renewable energy source, by converting solar energy into kinetic energy. 

A collaboration between the Humboldt University of Berlin in Germany and the Eindhoven University of Technology in the Netherlands attempted to address the need for an external stimulus driven actuator by creating a synthetic material which responds in an oscillatory fashion when exposed to a light stimulus. 

Azobenzenes are chemicals which can undergo a reversible reaction when exposed to light. These photo-reversible molecules are traditionally triggered by ultra-violet (UV) and blue light, causing a cis-trans isomerisation. This reaction can be utilised in self-oscillating actuators because of the reversible cis-trans isomerisations which make the film “move”. However, UV light eventually deteriorates the azobenzene, so creating a permanent self-oscillator requires tuning to less damaging electromagnetic waves such as visible light. 

Research has shown fluorinated azobenzene undergo cis-trans isomerisations with blue and green light, proving a viable candidate for incorporation into their actuator film research. 

They developed a liquid crystal polymer film doped with fluorinated azobenzene to test its oscillating prowess in the presence of only visible light. 

The liquid crystal film alignments were characterised using polarised light transmission microscopy and a THMS600. The THMS600 was used to determine the liquid crystal phase and alignment of the samples. The characterisation was vital for understanding and creating actuators with specific response properties. 

The polymer was sliced into a splay orientation to maximise film bending and was placed in sunlight. The exposure to light induced continuous bending in the polymer with no obvious frequency or pattern of oscillation.

Two superimposed freeze frames of the moving actuator. The red lines illustrate the top of the position of the film at the point the video was frozen. A notable change in position can be seen.  

Two superimposed freeze frames of the moving actuator. The red lines illustrate the top of the position of the film at the point the video was frozen. A notable change in position can be seen.  

To account for the effect of air currents, a control experiment was conducted by comparing the movements of a non-oscillating film with the fluorinated azobenzene film. The non-oscillator was created from a liquid crystal mixture and hydrogen azobenzene which is non-responsive to light. Both films were placed together and exposed to sunlight. The H-Azobenzene showed no movement indicating the oscillating behaviour in the fluorinated azobenzene was not due to air currents but the light induced changes in the film.   

Further experimentation found the experiments to be reversible with the number of cis and trans isomerisations determining the degree of bending. 


Professor Albert Schenning, from the Eindhoven University of Technology, said of the work:

 “A polymer actuator has been fabricated that is capable of continuous chaotic oscillatory motion when exposed to ambient sunlight in air. This work constitutes an important step towards the realisation of autonomous, persistently self-propelling machines and self-cleaning surfaces powered by sunlight. 

The actuator is based on a liquid crystalline polymer film doped with a visible light responsive fluorinated azobenzene. The alignment and the phase behaviour of the mixture was fully characterised by an optical microscope equipped with a Linkam hot stage. Such an analysis is crucial to prepare actuators with programmed response properties.”

Find out more here

Magnetic Modes in Rare Earth Perovskites: A Magnetic-Field-Dependent Inelastic Light Scattering study using Linkam’s HFS600-PB4

HFS600E-PB4 shown above  

As the modern world advances and our reliance on technology increases, it becomes necessary to improve the efficiency of semi-conducting materials. Semi-conductors are commonly used as diodes and transistors in devices such as microprocessors. Research into these materials is one of paramount importance. 

Recent studies have found transition metal oxides to have incredible electric, magnetic and superconducting properties, potentially ideal for semiconductors. LaAlO3 and SrTiO3 are wide band gap insulators with perovskite-based structures which are commonly used as substrates for functional oxide thin films. 

However, thin films of these oxides are not of much use except as high-k dielectrics. They require the addition of ions to tune their electronic band structure and thus improve their magnetic and optical properties. It is the interface between these oxides which prove to be the most interesting, their interaction induces magnetic and conductive properties from otherwise non-magnetic, insulating oxides. 

LaAlO3 is a rare-earth based perovskite transition metal oxide. Naturally such materials are isolated as crystals and it is important to understand the native characteristics if we are to better understand thin film behaviour. 

Due to its high-k dielectric properties, LaAlO3 is a promising material for metal oxide-based semiconductor devices. However, concern has been raised in several studies regarding leakage-current which is caused by structural defects. Understanding these defects theoretically and experimentally is of utmost importance for better use of such materials in optical and electronic applications. 

It has also been discovered that lattice strain affects the role and dynamics of defects. Previous work has also demonstrated that phase transitions can occur when samples are placed under certain temperatures. Current theories also suggest that specific engineering of these defects can provide several different functionalities for transition metal oxides. Raman spectroscopy further provides a useful method of probing these defects. 

Researchers from the National University of Singapore, Nanyang Technological University and Trinity College Dublin in Ireland explored novel magnetic excitations using Raman spectroscopy to probe LaAlO3 and several other polar oxide substrates. 

They built on the idea that a host of robust defects present in LaAlO3 could be promising in providing new functions with controlled engineering. The group conducted magnetic field dependant Raman spectroscopic studies at low temperatures to gain a better understanding of lattice phonons and the functionalities of these defects. 

The low temperature Raman spectroscopy was conducted using a WiTec Raman spectrometer and a Linkam HFS600E-PB4 with LNP, allowing a temperature range from <-195°C to 600°C.

The HFS set up with liquid nitrogen cooling and a WiTec Raman Spectrometer.&nbsp;

The HFS600E-PB4 set up with liquid nitrogen cooling and a WiTec Raman Spectrometer. 

When discussing the purpose of the Linkam stage, Dr. Surajit Saha said:

“The HFS was used to perform temperature dependence of the angular momentum states over a range of 80 to 300 K (-193°C to 26°C). It was useful because we could probe the decay of the angular momentum states with increasing temperature which was not possible to perform with our existing variable temperature setup.”

The low temperature experiments provided evidence for novel transitions which disappear at room temperature. These transitions were found to be magnetically sensitive, suggesting a magnetic degree of freedom caused by the defects. 

They further discovered that the key to magnetic sensitive field states is the presence of a heavy element within the transition metal oxide. These angular momentum states and the magnetic interactions can be tailored for novel optical applications. The magnetic degrees of freedom may potentially be tuned and optimised in rare earth perovskites for optical applications. 

The group’s research paves the way for further experimentation and testing to better understand the complexities of transition metal oxides.