F20MRS Meeting: Soft Electrically-Driven Actuators for Wearable Haptics

For me personally, the talks and live panels on virtual reality (VR) were the most interesting and engaging talks as it is wonderful to see how scientists are developing heptic devices that could bring stimulated sense of touch in a way that we could feel the texture and sense the virtual structures.

Why don’t we have haptic suits with thousands of individual actuators (taxels) when every smartphone display has millions of individually addressed pixels? To answer that, Dr. Shea from EPFL has tried to give us his perspective obout this field and the challenges ahead.

Dr. Shea addresses the challenges very delicately: generating localized forces on the human body in a comfortable and safe way is a major challenge for soft actuation: both fast motion and high forces are needed, yet the device must conform to the human body, and consume low power

Dr. Shea's lab has focused on electrostatic actuation, using high electric fields to deform elastomers or textile structures. They have developed a textile-based brakes, with a fine thickness of 1 mm , that can effectively block the motion of two sliding strips in a few milliseconds and control the joint motion. Using such a technology, users could manipulate virtual objects much better with more accuracy and feel deeper immersion. 

Their new fabrication method allows for high forces for use in full-body kinesthetic haptics by blocking shoulder and elbow motion to so that we could feel  for instance how heavy an object is to push and feel it's "weight". Thier method also generate normal and shear forces with high spatial resolution, that allows mimicking different feeling such as if something is about to slip out of our hands.

There is definitely much more to learn by watching Dr. Shea's talk on MRS meeting website using this link.

F20MRS Meeting: Towards Solid-State Batteries for Electric Vehicles

Dr. Doeff is a Senior Scientist and member of the Electrochemical Technologies Group (ECT) at Lawrence Berkeley National Laboratory. She is mainly working on sodium and lithium polymer batteries and more interestingly all-solid Li-ion batteries.

During this year's MRS meeting, Dr. Doeff has delivered a very informative talk about ceramic-based electrolytes and the challenges which exist for their design and application in vehicles. 

All-solid-state lithium batteries are advantageous against lithium-ion batteries as they could offer better energy density, safety, and reliability. The main problem with the current thin-film configurations is that their practical energy density is low and require expensive vacuum technologies to develop and scale.

Dr. Doeff and her coworkers at LBNL are developing a scalable freeze tape casting method to produce porous ceramic structures of LLZO (oxide-based solid electrolyte that is stable toward Li metal) to be used for all-solid-state lithium-ion batteries.

The microscopy work combined with synchrotron tomography that they have employed makes this talk very interesting and informative!

To watch this talk please use this link.

 

Engineering innate immune-mediated cancer cell killing by antibody recruiting macromolecules

F.SM07.04.11 Engineering innate immune-mediated cancer cell killing by antibody recruiting macromolecules

Annemiek Uvyn, Ghent University

Antibody therapy focuses on targeting antibodies onto the surface of cancer cells by innate immune mechanisms such as complement activation, antibody-dependent cell-mediated cytotoxicity, or antibody-dependent cellular phagocytosis to induce cancer cell killing. Monoclonal antibody therapy is limited in its high cost and side effects. And the research work lead by Annemiek Uvyn, from Ghent University, suggests that using synthetic systems that can recruit endogenous antibodies onto cancer cell surfaces can be a viable alternative for antibody therapy.

The research group works on developing antibody-recruiting polymers that can be used for cancer immunotherapy. These antibody recruiting polymers contain a target binding domain (to bind to the cell surface ) and an antibody binding domain (to bind to the antibody F-ab region). They can be injected directly into tumors to induce their attachment to cancer cell surfaces at one end and covalently attach the endogenous antibodies at the other. This binding would thus recruit immune cell-mediated cancer killing.

Interestingly, Annemiek says that a lipid anchor inserted into the phospholipid cell membrane is being used to covalently conjugate to the glycocalyx of metabolically azido-labeled cells. And azido-labelling becomes crucial to enhance the binding efficiency of antibody recruiting polymers (DBCO or DNP polymers) on to the cells. In vitro analysis of the polymers with cancers showed that a dialkyl group lipid polymer attached to cancer cells could high efficiently recruit anti-DNP into the cell surface. Eventually, the polymer conjugated cancer cell killing efficiency was visualized with macrophages to show phagocytosis is being activated with the lipid polymers. This approach of developing antibody-recruiting polymers can revolutionize monoclonal antibody cancer immunotherapy.

Fundamentals/Therapeutics: F.GI01.11: Live Keynote III

Fundamentals/Therapeutics: F.GI01.11: Live Keynote III

F.GI01.01.03 Membrane Based Affinity Capture to Quantify Antibodies to COVID-19

Merlin Bruening, University of Notre Dame

This live session talk is part of the Fundamentals/Therapeutics Live Keynote III. Prof Merlin Bruening, from the University of Notre Dame, and their group have devised a process to use membrane-based affinity to capture, elute, and quantify the concentration of COVID-19 specific antibodies. This technique could elucidate an easy way to calculate the amounts of antibodies against SARS-CoV2 in serum. 

The aim is to remove/elute antibody of interest specific to SARS-CoV2 from the mix of antibodies and proteins available in serum. To make this possible, the team uses nylon membrane and functionalizes them to capture/attract antibodies. The nylon membrane is functionalized with layer-by-layer deposition of polyelectrolytes like poly(acrylic acid) (PAA). Rinsing the membrane at low pH effects in carboxylic acid groups which can be used to then be modified with polyethyleneimine (PEI) polycations. Further after functionalization, a peptide mimotope can be added to the modified nylon which binds to specific protein regions. Preliminary data shows that when using Avastin/serum and eluting them using SDS/DTT, the resulting eluate contains pure Avastin captured and eluted. The next objective was to quantify the Avastin antibody. Avastin antibody quantitation was performed with spot blotting over PAA membrane and observing fluorescence with a secondary fluorescent-labeled antibody.

 

For calibration of the technique with COVID-19 antibodies, an anti-RBD protein is being functionalized with the membrane which showed a calibrated increase in the spot intensity of SARS-CoV2 monoclonal Antibodies. Data collected from fluorescence capturing of COVID antibodies would be helpful in analyzing if the patient has sufficient amounts of antibodies to have monoclonal antibody therapy. Further developments can yield in an efficient antibody detecting system!

 

 

 

 

 

 

 

 

Picture credit: Anal. Chem - Liu et al. Anal. Chem. 2018, 90, 20, 12161-12167

 

 

 

 

Following the third lecture in the session, a panel discussion was conducted. 

The panel consisted of, 

Elizabeth Wayne, Carnegie Mellon University

Kaitlyn Sadtler, National Institutes of Health

Jonathan Rivnay, Northwestern University

Merlin Bruening, University of Notre Dame

Susan Daniel, Cornell University 

Burak Ozdoganlar, Carnegie Mellon University

 

Merlin Bruening hopes that the research systems would get more opportunities and collaborations with companies that would aid in bringing out a clinical product from labs, such as quantitation of antibodies at a short time during a pandemic. Elizabeth from the panel Therapeutics section focuses on how the advances in diagnostics and therapy-based approaches to fulfill the therapeutic needs during the pandemic. 

Susan Daniel addresses suggesting that the structure-function relation is the key to figure out mechanisms to invent vaccines for new viruses like SARS-CoV2. Susan adds that viruses being non-alive particles, like small nanomachines to figure out how they work in the field. She urges on the shift of using the engineering part of nanodevices to cater the needs of viral detection engineering. Burak comments by stating that with the current lack of scalable manufacturing systems, many companies looking into using microneedle arrays to manage logistics and the pandemic need. But, difficulties in fabrication technology to cover costs and scalability makes them hard to get implemented into vaccines. 

Written by Arun Kumar. You can catch the session anytime through December 31^st! Follow us on Twitter for more updates: @Arun Kumar @Materials_MRS

Nanoparticles as drug delivery vehicles

F.SM07.05.05 New class of biodegradable drug delivery vehicles

 

Eva Krakor, University of Cologne

 

Nanoparticles and nanotechnology are growing to remodify the field of biology and medicine. Their extensive application is revolutionizing gene and drug delivery approaches, pathogen biodetection, tumor infiltration and cell killing, tissue engineering, and several other areas of research. Eva Krakor from the University of Cologne is concentrating on how mesoporous silica nanoparticles can be used to deliver the drug to cancer targets as a biodegradable delivery vehicle.

Hollow mesoporous silica capsules (HMSC) were synthesized from ellipsoidal hematite particles via a solvothermal process and then subsequently coated with silica via a sol-gel preparation. Characterization of the synthesized nanoparticles was performed with X-ray diffraction, IR spectroscopy, etc. Cytotoxic analysis of the mesoporous silica capsules on human embryonic kidney (HEK293) cells shows minimal toxicity even up to a high concentration of 100 µg/ml. This data can be used to showcase the biocompatibility of these nanoparticles. To observe if the nanoparticles are being internalized by the cells, cellular uptake study was then performed. After incubation of the nanoparticles for 24 hours in cervical cancer (HeLa) cells, the internalization of the particles was visualized via confocal microscopy.

Following the observation, drug loading and release profile were then observed with ciprofloxacin (hydrophilic compound) and curcumin (hydrophobic compound) loaded onto the nanoparticles. With UV-vis spectrophotometric analysis, the group elucidated the release profile of the drugs from the nanoparticles following a pH-dependent manner at 37C and normal physiological conditions. Eva Krakor suggests that the surface of these nanoparticles can be modified with proteins, like antibodies to be used as drug-carrying vehicles for immunotherapy.

Written by Arun Kumar. You can catch the session anytime through December 31st! Follow us on Twitter for more updates: @Blogger @Materials_MRS

Vaccination without injection – microneedle array skin patch to the rescue!

Typical intramuscular or subcutaneous injections are not ideal for delivering vaccines, therefore requiring a higher dose. Associated pain from needles also reduce patient compliance, especially among children. The intradermal route allows us to use a small dose as our skin has a sophisticated immunological network that can trigger rapid and potent immunogenicity.  However, intradermal injection with the Mantoux procedure gives poor reliability and reproducibility, even after training.

Our skin is just 1 mm thick and a great alternative approach is using a skin patch with microneedle arrays (MNAs). A MNA contains hundreds of microneedles made of a dissolvable sugar-based material containing biocargo such as proteins or vaccines into the skin. In this way, the MNA skin patch can deliver the biocargo into the skin within just 15 min. Guess what, no special medical training is needed to self-administer the MNA skin patches. 

To make the MNA patch with very sharp tips, diamond micromilling is first used to make a master mold. Silicone (polydimethylsiloxane, PDMS) molds are made from the master mold, then the sugar-based material is spin-coated on the PDMS molds to form the microneedles. Different tip geometries were made with good consistency using this method.

However, the MNA could only carry up to 1 μL of dry-form or dryable biologics initially. Therefore, Prof. Ozdoganlar's group developed Hybrid-MNAs with dissolvable tips and non-dissolvable cannulas (patent pending). The cavities in the microneedles allow various types of biocargo such as vaccines to be carried and delivered into the skin. Furthermore, the Hybrid-MNAs are more easily sterilizable.

Unlike intramuscular or subcutaneous injection-based vaccines requiring cold-chain transport & storage, the MNA materials are not as temperature-sensitive, improving vaccine accessibility and affordability. Needle reuse problems in intramuscular, subcutaneous and Mantoux injections can be avoided. While microneedle arrays have been around for over 15 years, commercialization has been limited. The team is currently working on scaling up. The MNAs hold great promise for future vaccine distribution, we wish them all the best! 

Watch the recording of Fundamentals/Therapeutics: F.GI01.11: Live Keynote III & F.GI01.12: Live Panel Discussion III on tackling COVID-19.

You may connect with me on Twitter and check out the conference hashtag #F20MRS.

Personal protective equipment in the lab

What do you usually wear in terms of personal protective equipment (PPE) when working in the lab? The basic suit up gears: Lab coat, goggles, and gloves.

When the world began the war against the pandemic, the spotlight of PPE shone on the facial masks. Not only the awareness of mask wearing is increased, also the research activities in mask development.

This year MRS gathers a special keynote and panel discussion about the research in facial masks along with the biomaterials in the era of COVID-19.

“Leveraging Nanotechnology for Controlling SARS-CoV-2 Transmission” by Danmeng Shuai

The Shuai Group looks at the design and fabrication of air filters that can be used in the masks and air filtration system in the residential buildings. As the coronavirus mainly relies on aerosols to spread, usually for long-range transmission, effective capture of bioaerosols containing viruses would be beneficial to protecting public health.

Image: Shuai Group

“Harnessing Synthetic Biology to Address the COVID-19 Pandemic” by James J. Collins

The Collins Group focuses on developing biologic cells that work as a diagnostic tool. The biomaterials, once successfully integrated into wearable equipment, for example, lab coats or face masks, can sense and report the potential pathogen contamination.  

“Facial Masks during COVID-19: Disinfection, Homemaking, Imaging and Future Materials Design” by Yi Cui

In the talk, Cui discussed the approaches to disinfect facial masks under heating and humidity conditions so that the masks can be reused without compromising the protection purpose. The Cui Group is also active in designing homemade masks, offering a route for the general public to utilize household textiles in making effective masks.

To know more, go to PPE/Surfaces: F.GI01.09 & F.GI01.10

 

Catch up with Chiung-Wei @Twitter

The role of calcium ions in coronavirus infection

You may have heard that in SARS-CoV-2, the coronavirus spikes bind to a type of host cell receptors called ACE-2. But have you heard of research on the next step of virus entry, membrane fusion? Prof Susan Daniel from Cornell University has been investigating the virus entry mechanisms of SARS-CoV, with renewed importance given the emergence of the SARS-CoV-2.

There are two possible pathways for membrane fusion – the endocytosis pathway or the plasma membrane pathway. In the more direct latter pathway, the fusion peptide of the virus acts like a harpoon anchoring to the host cell membrane and allows the virus to release its genetic material into the host cell (refer to schematic below). 

Coronavirus membrane fusion pathways. Image source: Prof Susan Daniel and team.

Daniel’s group is interested in inhibiting coronavirus fusion peptide's insertion into cell membrane. They noticed charged residues in the coronavirus genes and studied the role of calcium ions in membrane fusion. Firstly, with increased calcium ions in the cell culture buffer, the infectivity increased. To follow up, they used a membrane-permeable calcium chelator BAPTA-AM to increase the intracellular Ca²⁺ concentration and also found greater viral infectivity.

Ca²⁺ was found to favor two prerequisites for membrane fusion: alpha helix formation for fusion protein insertion, as well as lipid ordering in the host. Using isothermal calorimetry, it was found that two Ca²⁺ ions were required for every SARS-CoV fusion protein in an endothermic process. With the help of computational simulations, the binding sites of the fusion peptide with Ca²⁺ ions were predicted, giving surprising results!

Calcium ion binding sites of coronavirus fusion protein. Image source: Prof Susan Daniel and team.

Since the gene residues involved in membrane binding are largely conserved in different coronaviruses such as MERS-CoV and SARS-CoV-2, the same principle of calcium sensitivity could be used to inhibit SARS-CoV-2. With reducing Ca²⁺ in mind, the team sought to find possible drugs which may lower SARS-CoV-2 infectivity. The three CCB drugs are already FDA-approved for cardiac conditions. Vero-E6 kidney cells and Calu-3 lung cancer cells were exposed to the drugs and live coronavirus. While some of the CCB drugs show promise in reducing the infectivity, it’s still too early to gauge if they could be effective for coronavirus prevention and we are not encouraged to take those drugs without prescription. Further follow-up studies are still needed. 

By studying the biomolecular pathways of viruses, scientists have gained a better understanding of the infection mechanisms. Targeting the problem at its roots enabled us to narrow down on potential drug candidates.

Watch the recording of Fundamentals/Therapeutics: F.GI01.11: Live Keynote III & F.GI01.12: Live Panel Discussion III.

F20MRS Meeting: Three-Dimensional Imaging of Degradation in Composite Si-Containing Anodes

Current lithium-ion batteries, LIBs, with graphite anodes can be replaced with silicon (Si) anodes in the next-generation lithium-ion batteries because of higher specific capacity of silicon. The challenge that relies ahead is the significant volume expansion of Si during lithiation and an unstable solid-electrolyte interphase (SEI), resulting in unreliable performance and poor cycle life.

The composite anodes with both Si and graphite active materials are currently being investigated as graphite could mitigate some of the limitations mentioned with Si. However, it is important to understand the local distribution of each component in a composite structure to understand the electrochemical processes, particularly localized degradation and heterogeneous aging, and to optimize performance.

The heterogeneous distribution of Si leads to localized lithiation, nonuniform SEI formation and material degradation, and complex electron transfer pathways, which all impact anode cycling and performance.

To investigate Si-containing composite anodes in the nanoscale, Zoey Huey and her colleagues at NREL is using scanning spreading resistance microscopy (SSRM), a form of scanning probe microscopy (SPM) that probes local electronic resistivities. By examining the contrast in intrinsic electronic resistivity between the anode components, separate phases can be distinguished and understood within the composite structure and study the effects of electrochemical cycling on component distribution and aging by comparing the electrical and structural evolution of composite Si-graphite electrodes before and after charge-discharge cycling

You can learn more about their work by using this link.

 

Bioprinting human skin and retina tissues through microvalve-based printing

Bioprinting uses cells, proteins and biomaterials as building blocks to 3D print biological tissue models, biological systems and therapeutic products. In this OnDemand symposium S.SM09.01.11 The Investigation of Nano-Liter Droplets for Bioprinting Applications, I learnt how microvalve-based printing enabled breakthroughs in bioprinting tissue constructs by depositing smaller droplets of bioink more evenly. 

Material jetting, material extrusion and vat polymerization are the 3 main classes of techniques used in bioprinting. In material jetting, ink is deposited drop-by-drop and the resolution is determined by the droplet size. In material extrusion, 3D printing is done line-by-line and the resolution is determined by the filament size. Besides the print resolution, bioprinting comes with additional considerations when printing bioink with cells, such as the cell viability (= survival) and cell distribution. The cell distribution is more even and controllable using inkjet instead of filament extrusion. However, droplet splashing reduces the print accuracy and decreases cell viability.

A/P Yeong’s group from Nanyang Technological University used microvalves to create smaller droplets in the nano-liter range. They investigated droplet dynamics using a high-speed camera. By increasing the polymer concentration, the bioink properties could be modified to reduce splashing. This way, the number of satellite droplets decreased and bioink deposition was favorable for cell viability.

With microvalve-based printing, the group successfully fabricated biomimetic human skin constructs with uniform skin color instead of black spots. Melanocytes, cells which produce the black pigment melanin, were uniformly distributed. Upon maturity, a uniform skin color was produced.

The group also fabricated a tissue model for eye retina in collaboration with a local hospital with microvalve-based printing. Firstly, retinal cells were bioprinted on a thin porous polycaprolactone membrane simulating the Bruch’s membrane. On the second layer, photoreceptors were bioprinted. The resulting tissue mimicked the distribution of cone and rod cells in human retina. This retinal tissue model could be used in drug testing for age-related macular degeneration (AMD).  

Technological improvements in bioprinting holds great promise for biomedical research. More articles on bioprinting symposiums by fellow student writer @JessalynLow can be found here and here.

You can find me on Twitter (@labspatula) and catch more Meeting highlights with the hashtag #F20MRS.