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A low-temperature bubble-generating system for enhanced surface capture of proteins

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Jul 27, 2020 (Nanowerk Spotlight) A large variety of measurements in nanotechnology and the life sciences requires analytes in solution to react with receptors immobilized on a surface. The diffusional transport of biomolecules to a substrate is one of the factors that determines sensing performance of this kind of surface-based biosensing. In the quest to miniaturize sensors and analyte volumes – ultimately down to the nanoscale – as well as increase speed and sensitivity of the results, researchers have explored and developed a variety of platforms. One of them is optothermal microbubble assisted bio-sensing. Convective fluid flow generated by an optically controlled surface microbubble is a fascinating phenomenon for overcoming the diffusion limit in surface-based biosensing. The irradiation of a plasmonic substrate with a focused laser beam at the plasmon resonance wavelength generates microbubbles at the substrate-solution interface (read more: “Nanotechnology in a bubble“). These microbubbles can quickly accumulate solutes at the bubble-liquid-substrate interface due to high-velocity fluid flows. However, the high temperature of above 100 °C required for producing water bubbles has limited this technique’s sensing applications to only certain target biomolecules. For instance, it is not suitable for sensing proteins that are subject to thermal denaturation. Motivated by the question of how to reduce and modulate the working temperature of bubble-generating systems from a material perspective, a team of researchers at The University of Texas at Austin have demonstrated a proof-of-concept study that reduces the working temperature of bubble generation simply by introducing a volatile, water-immiscible liquid into an aqueous medium. They published their findings in Nano Letters (“Enhancing Surface Capture and Sensing of Proteins with Low-Power Optothermal Bubbles in a Biphasic Liquid”). “Here, we demonstrate a biphasic system that generates microbubbles at a low optical power/temperature, thus enabling its application to protein sensing,” Youngsun Kim, a member of Yuebing Zheng’s research group and the paper’s first author, tells Nanowerk. “Specifically, we describe the capability of a bubble, generated from a perfluoropentane (PFP)-in-water biphasic liquid, as an in situ concentrator in surface-based biosensing.” By introducing a biphasic liquid system wherein a volatile, water-immiscible liquid (PFP) is formulated into an aqueous medium, the researchers were able to generate bubbles at a much lower temperature of around 30 °C – compared to over 100 °C for water bubbles – not only making this sensing platform compatible with proteins but also enhancing the surface capture of proteins. text Scheme of bubble-enhanced surface capture of proteins and description of biphasic fluid. Left: Schematic illustration of the bubble-generating perfluoropentane (PFP)-in-water system and, right: bubble-mediated concentration of target proteins near the bubble-liquid-substrate interface. Arrows in panel a indicate the expansion of the PFP droplet into the bubble. (Reprinted with permission by American Chemical Society) (click on image to enlarge) “We were able to reduce the threshold optical power for bubble generation to 33% of that in a pure aqueous medium,” Kim points out. “The generated bubble was able to induce Marangoni flow due to a surface tension gradient, which was large enough to accumulate proteins from the bulk solution near the bubble-liquid-substrate interface. We observed one-order-of magnitude enhancement of surface capture within 1 minute in a single antigen-antibody model, compared to that from diffusion-limited static incubation for 30 minutes.” One of the benefits of this concept is that the working temperature can be tuned simply by varying the components of the biphasic liquid, leading to its wide applicability in biosensing. “One of the merits of the bubble-based approach, composed of fluid formulation and an optothermal add-on, resides in its compatibility with conventional surface-based assay platforms,” Kim notes. “Given the working mode of our concept, the same method can be sequentially applied to multiple steps of solution-to-surface conjugation as in sandwich-type ELISA, e.g., capture antibody/antigen, antigen/probe antibody, probe antibody/secondary antibody, and enzyme/substrate.” Consequently, the team now plans to integrate the biphasic bubble-generating system into standard surface-based biosensing such as an enzyme-linked immunosorbent assay (ELISA). They expect a collective improvement of sensitivity and throughput performance resulting from enhancements in binding events at multiple steps of ELISA. Overall, the present study could find a wider range of scientific and clinical applications in biosensing when combined with rational designs of sensor configurations. It also suggests a way toward improving the performance of sensor and spectroscopy applications. By
Michael is author of three books by the Royal Society of Chemistry:
Nano-Society: Pushing the Boundaries of Technology,
Nanotechnology: The Future is Tiny, and
Nanoengineering: The Skills and Tools Making Technology Invisible
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Nanowerk

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Arrowhead Interim Clinical Data Demonstrate ARO-AAT Treatment Improved Multiple Biomarkers of Alpha-1 Liver Disease

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Home > Press > Arrowhead Interim Clinical Data Demonstrate ARO-AAT Treatment Improved Multiple Biomarkers of Alpha-1 Liver Disease

Abstract:
– Serum Z-AAT reductions of 86-93%

– All patients demonstrated greater than 80% reduction in liver Z-AAT monomer

– 3 of 4 patients had a decrease in liver globule involvement

– 3 of 4 patients demonstrated reductions in Z-AAT polymer with a range of 68-97%

– All patients showed ALT reductions ranging from 36-66%

Arrowhead Interim Clinical Data Demonstrate ARO-AAT Treatment Improved Multiple Biomarkers of Alpha-1 Liver Disease


Pasadena. CA | Posted on November 13th, 2020

Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today announced positive interim clinical data from AROAAT2002, an open-label Phase 2 clinical study of ARO-AAT, the company’s second-generation investigational RNA interference (RNAi) therapeutic being developed as a treatment for the rare genetic liver disease associated with alpha-1 antitrypsin deficiency (AATD). The data demonstrate that three doses of ARO-AAT over 24-weeks resulted in consistent reductions of the disease-causing mutant Z protein (Z-AAT) and improvements in clinically relevant biomarkers of liver disease. The results were presented in a late-breaking poster at The Liver Meeting Digital Experience, the Annual Meeting of the American Association for the Study of Liver Disease (AASLD).

A copy of the poster may be accessed on the Events and Presentations page under the Investors section of the Arrowhead website.

Javier San Martin, M.D., chief medical officer at Arrowhead, said: “These data presented at AASLD strongly suggest that ARO-AAT is doing what it’s designed to do, which is reduce the production of the misfolded mutant Z-AAT protein. Moreover, these compelling results indicate that the liver may have the ability to clear out accumulated Z-AAT and begin to heal itself faster than anticipated. Importantly, we saw reductions in serum Z-AAT and liver Z-AAT which led to improvements in multiple markers, such as liver globules, ALT/GGT and Pro-C3. These are all positive indications of a strong pharmacodynamic response and improvement in liver health, following just three doses of ARO-AAT. We anticipate data from additional patient cohorts will be available in the coming months, which will be included in our planned discussions with the U.S. Food and Drug Administration and other regulatory agencies, aimed at exploring areas where the ARO-AAT program could potentially be streamlined and accelerated.”

In the AROAAT2002 study, four patients with homozygous PiZZ alpha-1 antitrypsin deficiency and evidence of fibrosis at screening, each received three doses of ARO-AAT on week 0, 4, and 16. Liver biopsies were performed at screening and at week 24. Assessments included safety (including pulmonary function tests), changes in serum Z-AAT, liver Z-AAT, ALT, GGT, Pro-C3, liver elastography (FibroScan®), and liver globule assessment. Additional histologic adjudication is ongoing.

Key data presented include the following:

Pharmacodynamic Response at 24 weeks

Serum Z-AAT reductions were 86-93%
Total intra-hepatic Z-AAT reductions were 72-95%
All patients demonstrated greater than 80% reduction in liver Z-AAT monomer (soluble)
3 of 4 patients demonstrated reductions in Z-AAT polymer (insoluble) with a range of 68-97%
3 of 4 patients had a decrease in liver globule involvement and 1 subject remained unchanged
All patients showed reductions in ALT (range 36-66%) and in GGT (range 43-58%)
3 of 4 patients demonstrated a substantial reduction of greater than 20% in FibroScan® values
3 of 4 patients showed greater than 30% reduction in serum Pro-C3, a marker of fibrogenesis
Safety

Overall, ARO-AAT 200 mg as a subcutaneous injection was well tolerated in PiZZ AATD subjects
One treatment emergent SAE of Epstein bar virus related myocarditis was reported
No treatment emergent AEs related to change in pulmonary status or pulmonary function were reported
No clinically meaningful changes in ppFEV1 from baseline to Week 24 were observed
In October 2020, Arrowhead and Takeda Pharmaceutical Company Limited announced a collaboration and licensing agreement to develop ARO-AAT. Under the terms of the agreement, Arrowhead and Takeda will co-develop ARO-AAT which, if approved, will be co-commercialized in the U.S. under a 50/50 profit-sharing structure. Outside the U.S., Takeda will lead the global commercialization strategy and receive an exclusive license to commercialize ARO-AAT with Arrowhead eligible to receive tiered royalties of 20-25% on net sales. Arrowhead will receive an upfront payment of $300 million and is eligible to receive potential development, regulatory and commercial milestones up to $740 million. Closing of the transaction is contingent on completion of review under antitrust laws, including the Hart-Scott-Rodino Antitrust Improvements Act of 1976 in the U.S.

AROAAT2002 (NCT03946449) is a pilot open-label, multi-dose, Phase 2 study to assess the response to ARO-AAT in approximately 16 patients with AATD associated liver disease and baseline liver fibrosis who will be enrolled in three cohorts. All eligible participants will require a pre-dose biopsy and an end of study biopsy. Treated participants will also be offered the opportunity to continue treatment in an open-label extension (OLE). Including the OLE, interim assessments will be made after 6 months and 18 months (cohorts 1, 1b), and 12 months and 24 months (cohort 2) of treatment with ARO-AAT. Arrowhead is also evaluating ARO-AAT in the ongoing SEQUOIA Phase 2/3 trial, which began in August 2019.

####

About Arrowhead Pharmaceuticals, Inc.
Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing.

For more information, please visit www.arrowheadpharma.com, or follow us on Twitter @ArrowheadPharma. To be added to the Company’s email list and receive news directly, please visit http://ir.arrowheadpharma.com/email-alerts .

Safe Harbor Statement under the Private Securities Litigation Reform Act:

This news release contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of various factors and uncertainties, including the safety and efficacy of our product candidates, the duration and impact of regulatory delays in our clinical programs, our ability to finance our operations, the likelihood and timing of the receipt of future milestone and licensing fees, the future success of our scientific studies, our ability to successfully develop and commercialize drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, and the enforcement of our intellectual property rights. Our most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q discuss some of the important risk factors that may affect our business, results of operations and financial condition. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances.

For more information, please click here

Contacts:
Arrowhead Pharmaceuticals, Inc.
Vince Anzalone, CFA
626-304-3400

Investors:
LifeSci Advisors, LLC
Brian Ritchie
212-915-2578
www.lifesciadvisors.com

Media:
LifeSci Communications, LLC
Josephine Belluardo, Ph.D.
646-751-4361
www.lifescicommunications.com

Copyright © Arrowhead Pharmaceuticals, Inc.

If you have a comment, please Contact us.

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Arrowhead Presents New Clinical Data on Cardiometabolic Pipeline at AHA 2020

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Home > Press > Arrowhead Presents New Clinical Data on Cardiometabolic Pipeline at AHA 2020

Abstract:
– ARO-APOC3 achieved triglyceride reductions of 74-92%

– ARO-ANG3 achieved triglyceride reductions of 29-75% and LCL-C reductions of 29-35%

– Company to host upcoming KOL webinars on ARO-APOC3 and ARO-ANG3

Arrowhead Presents New Clinical Data on Cardiometabolic Pipeline at AHA 2020


Pasadena. CA | Posted on November 13th, 2020

Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today announced positive clinical data from multiple product candidates in its cardiometabolic pipeline at the American Heart Association (AHA) Scientific Sessions 2020.

Javier San Martin, M.D., chief medical officer at Arrowhead, said: “The data presented at AHA on our cardiometabolic pipeline continue to show strong and consistent response across a range of lipid parameters. There remains significant residual cardiovascular risk despite recent scientific advances, and we believe that our cardiometabolic pipeline has the ability to target new therapeutic targets and address multiple lipid parameters associated with increased cardiovascular risk.”

Copies of the following presentations may be accessed on the Events and Presentations page under the Investors section of the Arrowhead website:

Title: Pharmacodynamic effect of ARO-ANG3, an investigational RNA interference therapeutic targeting hepatic angiopoietin-like protein 3, in patients with hypercholesterolemia
Authors: Gerald F. Watts, et al.
Session: Advances in Understanding and Treatment of Dyslipidemia and New Therapies for CVD

Title: Pharmacodynamic effect of ARO-APOC3, an investigational hepatocyte-targeted RNA interference therapeutic targeting apolipoprotein C3, in patients with hypertriglyceridemia and multifactorial chylomicronemia
Authors: Christie Ballantyne, presenting on behalf of Peter Clifton, et al.
Session: Advances in Understanding and Treatment of Dyslipidemia and New Therapies for CVD

Title: Safety, Tolerability and Efficacy of Single-Dose AMG 890, a Novel siRNA Targeting Lp(a), in Healthy Subjects and Subjects with Elevated Lp(a)
Authors: Michael J. Koren, et al.
Session: Advances in Understanding and Treatment of Dyslipidemia and New Therapies for CVD

Arrowhead will also host two key opinion leader (KOL) webinars on November 18, and November 19, 2020 to discuss data from, and the company’s future plans for, its two investigational cardiometabolic candidates, ARO-APOC3 and ARO-ANG3. The webinars may be accessed on the Events and Presentations page under the Investors section of the Arrowhead website.

####

About Arrowhead Pharmaceuticals, Inc.
Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing.

For more information, please visit www.arrowheadpharma.com, or follow us on Twitter @ArrowheadPharma. To be added to the Company’s email list and receive news directly, please visit http://ir.arrowheadpharma.com/email-alerts .

Safe Harbor Statement under the Private Securities Litigation Reform Act:

This news release contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of various factors and uncertainties, including the safety and efficacy of our product candidates, the duration and impact of regulatory delays in our clinical programs, our ability to finance our operations, the likelihood and timing of the receipt of future milestone and licensing fees, the future success of our scientific studies, our ability to successfully develop and commercialize drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, and the enforcement of our intellectual property rights. Our most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q discuss some of the important risk factors that may affect our business, results of operations and financial condition. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances.

For more information, please click here

Contacts:
Arrowhead Pharmaceuticals, Inc.
Vince Anzalone, CFA
626-304-3400

Investors:
LifeSci Advisors, LLC
Brian Ritchie
212-915-2578
www.lifesciadvisors.com

Media:
LifeSci Communications, LLC
Josephine Belluardo, Ph.D.
646-751-4361
www.lifescicommunications.com

Copyright © Arrowhead Pharmaceuticals, Inc.

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

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CCNY & partners in quantum algorithm breakthrough

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Home > Press > CCNY & partners in quantum algorithm breakthrough

The Google Quantum Computer. Photo courtesy of Google Quantum AI
The Google Quantum Computer. Photo courtesy of Google Quantum AI

Abstract:
Researchers led by City College of New York physicist Pouyan Ghaemi report the development of a quantum algorithm with the potential to study a class of many-electron quantums system using quantum computers. Their paper, entitled “Creating and Manipulating a Laughlin-Type ν=1/3 Fractional Quantum Hall State on a Quantum Computer with Linear Depth Circuits,” appears in the December issue of PRX Quantum, a journal of the American Physical Society.

CCNY & partners in quantum algorithm breakthrough


New York, NY | Posted on November 13th, 2020

“Quantum physics is the fundamental theory of nature which leads to formation of molecules and the resulting matter around us,” said Ghaemi, assistant professor in CCNY’s Division of Science. “It is already known that when we have a macroscopic number of quantum particles, such as electrons in the metal, which interact with each other, novel phenomena such as superconductivity emerge.”

However, until now, according to Ghaemi, tools to study systems with large numbers of interacting quantum particles and their novel properties have been extremely limited.

“Our research has developed a quantum algorithm which can be used to study a class of many-electron quantum systems using quantum computers. Our algorithm opens a new venue to use the new quantum devices to study problems which are quite challenging to study using classical computers. Our results are new and motivate many follow up studies,” added Ghaemi.

On possible applications for this advancement, Ghaemi, who’s also affiliated with the Graduate Center, CUNY noted: “Quantum computers have witnessed extensive developments during the last few years. Development of new quantum algorithms, regardless of their direct application, will contribute to realize applications of quantum computers.

“I believe the direct application of our results is to provide tools to improve quantum computing devices. Their direct real-life application would emerge when quantum computers can be used for daily life applications.”

###

His collaborators included scientists from: Western Washington University, University of California, Santa Barbara; Google AI Quantum and the University of Michigan, Ann Arbor.

####

For more information, please click here

Contacts:
Jay Mwamba
917-892-0374

Copyright © City College of New York

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Anions matter: Zinc-ion hybrid capacitors with ideal anions in the electrolyte show extra-long performance

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Home > Press > Anions matter: Zinc-ion hybrid capacitors with ideal anions in the electrolyte show extra-long performance

© Wiley-VCH, re-use with credit to 'Angewandte Chemie' and a link to the original article.
© Wiley-VCH, re-use with credit to ‘Angewandte Chemie’ and a link to the original article.

Abstract:
Metal-ion hybrid capacitors combine the properties of capacitors and batteries. One electrode uses the capacitive mechanism, the other the battery-type redox processes. Scientists have now scrutinized the role of anions in the electrolyte. The results, which have been published in the journal Angewandte Chemie, reveal the importance of sulfate anions. Sulfate-based electrolytes gave zinc-ion hybrid capacitors outstanding performance and extra-long operability.

Anions matter: Zinc-ion hybrid capacitors with ideal anions in the electrolyte show extra-long performance


Heidelberg, Germany | Posted on November 13th, 2020

Capacitors can uptake and release an enormous amount of charge in a short time, whereas batteries can store a lot of energy in a small volume. To combine both properties, scientists are investigating hybrid electrochemical cells, which contain both capacitor- and battery-type electrodes. Among these cells, researchers have identified metal-ion hybrid capacitors as especially promising devices. Here, the positive electrode includes pseudocapacitive properties, which means it can also store energy in the manner of a battery, by intercalation of the metal ions, while the negative electrode is made of a redox-active metal.

However, their electrolyte has long been neglected, says Chunyi Zhi who is investigating battery materials together with his team at the City University of Hong Kong. The researchers believe the type of electrolyte anion affects the performance of the device. “Paying more attention to the introduction of appropriate anions can effectively improve the power and energy density of a capacitor,” they say.

The researchers focused their attention on zinc-ion capacitors. This cell type consists of a zinc metal anode and a cathode made of titanium nitride nanofibers. The nanofibers are robust, and their porous surface allows the electrolyte to infiltrate. The scientists argue that the electrolyte anions, when attached to the titanium nitride surface, make the material more conductive. Moreover, the adsorbed anions may directly contribute to the charging process. The charging of the hybrid capacitor involves the extraction of the intercalated zinc ions.

Zhi and his colleagues compared the effects of three electrolyte anions: sulfate, acetate, and chloride. They looked at both their binding to the electrode surface and the performances of the electrochemical cells. It was a clear result.

The scientists reported that the sulfate anions stood out among the three anions. They observed that cells based on a zinc sulfate electrolyte performed best, and the sulfates bound stronger to the titanium nitride surface than the other anions. Moreover, sulfate-treated electrodes showed the lowest self-discharging. The authors attributed the findings to the electronic effects of sulfate. Its electron-pulling nature provides tight binding to the surface atoms and prevents the electrode from self-discharging, the authors concluded.

For a zinc-sulfate-based zinc-ion hybrid capacitor, the scientists reported high-performance operation for more than nine months. Moreover, these devices are flexible, which is especially useful for portable electronics. The scientists tested the device in an electronic watch and found excellent performance.

###

About the Author

Dr. Chunyi Zhi is a Professor at the Department of Materials Science & Engineering at the City University of Hong Kong. His research interests span the practical application of flexible energy-storage devices, zinc-based batteries with new electrode materials and electrolytes, and catalysts for oxygen and nitrogen reduction reactions.

http://www.comfortablenergy.net/

####

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Mario Mueller

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