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Accumold showcases micromoulding innovation at Compamed

Accumold, with over 40 years of experience in micromoulding technology, is set to participate at Compamed, taking place in Düsseldorf, Germany, from 11-14 November. The company will highlight its small and complex parts for medical device OEMs.




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Protecting vital medical implants with epoxies

Mike Hodgin, director of strategic applications, Meridian Electronics Division discusses enabling and protecting vital medical implants with epoxies.




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Syensqo to showcase portfolio of medical-grade polymers at Compamed

Syensqo, previously part of Solvay Group and a global provider of advanced performance materials and chemical solutions, is making its debut at Compamed 2024.




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Trelleborg Medical Solutions showcases polymer-based solutions at Compamed

Trelleborg Medical Solutions showcases its comprehensive polymer-based solutions and capabilities for the medical technology and biopharmaceutical industries at Compamed 2024 in Dusseldorf from November 11 to 14, at stand F02 in hall 8A.




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The Virus That Causes Mpox Keeps Getting Better at Spreading in People

Analysis of a strain of the virus circulating in Central Africa shows genetic mutations indicative of sustained human-to-human spread




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Astrology Was an Important Science for Medieval People

In medieval times, astrology was considered a serious science, a branch of astronomy. Curator Larisa Grollemond of the Getty Museum, walks us through the medieval zodiac and how someone’s sign decided their day-to-day life.




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Trump Victory Is a ‘Gut Punch’ to U.S. Climate Action

President-elect Trump vowed to promote fossil fuels, weaken pollution regulations and reverse Biden administration climate efforts




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Trump’s Administration Will Attack Health Care from Multiple Angles

The new Trump administration is likely to reduce subsidies for Affordable Care Act insurance plans and roll back Medicaid coverage. Public health authorities worry that antivaccine activist Robert F. Kennedy, Jr., will be empowered




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What Trump Can—And Probably Can’t—Do to Reverse U.S. Climate Policy

The new president-elect can go beyond just pulling out of the Paris Agreement. But it may be more difficult to roll back clean energy policies




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Trump’s Election Threatens Heat Protections for Workers

A Biden administration proposal that would require employers to provide cooling measures under extreme heat conditions may be scuttled by the incoming Trump administration




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Trump Administration Likely to Repeal Methane Leak Penalty

A fee created to push oil and gas companies to plug methane leaks could be axed by the incoming Trump administration, hampering efforts to curb the potent greenhouse gas




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Robotic Ankle Helps with Postural Control in Amputees

Researchers at North Carolina State University have developed a robotic prosthetic ankle that can provide stability for lower limb amputees. The ankle uses electromyographic sensors placed on the sites of muscles in the residual limb that then convey the intentions of the wearer with regard to movement. So far, the system has been shown to […]




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A Wearable to Manage Parkinson’s Motor Symptoms: Interview with Lucy Jung, CEO at Charco Neurotech

Charco Neurotech, a medtech company based in the United Kingdom, has developed CUE1, a non-invasive wearable that is intended to assist those with Parkinson’s disease to manage their motor symptoms. The device is typically affixed to the sternum, and provides vibratory action in a focused region of the body. The technology is based on the […]




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Magnetic Dressing Improves Diabetic Wound Healing

Researchers at the National University of Singapore have developed a magneto-responsive hydrogel wound dressing that also contains two different regenerative cell types. The hydrogel is also embedded with magnetic particles that can be stimulated using an external magnetic field. The action of the magnetic field on the gel-encapsulated particles causes mechanical stresses within the gel […]




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Glasses Provide Audible Prompts for Blind Wearers

A team at the University of Technology Sydney has developed an assistive technology for blind people and those with low vision. The system consists of glasses that can view their surroundings through an on-board camera, appraise the objects nearby using computer vision technology, and then play a sound that provides a cue for the wearer […]




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Innovative Models for Improving Access and Visibility for Specialty-Lite and Retail Therapies

Today’s guest post comes from Timothy Nielsen, Vice President of Customer Success at AssistRx.

Timothy discusses the affordability and patient journey challenges of specialty-lite products for patients, manufacturers, and health care providers. He explains how AssistRx's Advanced Access Anywhere (AAA) solution streamlines processes for specialty-lite products and facilitates enrollment via a digital hub.

To learn more, register for AssistRx's free webinar on October 8: Meet Your Patients Where They Are & Gain Visibility: Even at Retail.

Read on for Timothy’s insights.
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As MFP Approaches, Transparency Is More Important Than Ever

Today’s guest post comes from Angie Franks, Chief Executive Officer of Kalderos.

Angie discusses how the Maximum Fair Price provision of the Inflation Reduction Act of 2022 will challenge providers, pharmacies, and manufacturers. She explains how Kalderos’ Truzo platform could reduce duplicate claims and address compliance issues.

To learn more, register for Kalderos’ October 25 webinar Cracking the MFP Code: How Flexible Technology Helps You Navigate an Evolving Landscape.

Read on for Angie’s insights.
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How Field Reimbursement Services Help Overcome Coverage Barriers and Improve Patient Outcomes

Today’s guest post comes from Kimberley Chiang, Vice President of Biopharma Commercial Solutions at CoverMyMeds

Kimberley highlghts the crucial roles of field reimbursement managers in removing access and reimbursement barriers. She then identifies the keys to successful implementation of field reimbursement services.

To learn more, register for CoverMyMeds' November 13, 2024, webinar: Specialty Therapies & Field Reimbursement Services: Driving Better Outcomes for Brands and Patients.

Read on for Kimberley’s insights.
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How the Perfect Storm Will Impact Patient Support Programming in 2025 and Beyond

Today’s guest post comes from Chris Dowd, Senior VP of Market Development at ConnectiveRx.

Chris examines three key trends that will affect patient support programs: the Inflation Reduction Act (IRA), legal/regulatory battles over copay adjustment programs, and uncertainties following a national election. He then outlines three actions that should guide manufacturers' preparation.

To learn more, register for ConnectiveRx’s free webinar on December 11: The Perfect Storm? Patient Support Programming in 2025 and Beyond.

Read on for Chris’s insights.
Read more »
       




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Bonus Episode: Fast Facts on the ACRO D&I Grants Program

ACRO’s Good Clinical Podcast is back with bonus episode! Host Sophia McLeod sat down with Tafoya Hubbard and Kristen Surdam to discuss ACRO’s new D&I Site Resource Grants Program.

The post Bonus Episode: Fast Facts on the ACRO D&I Grants Program first appeared on ACRO.




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Sequestration Has Less Impact on FDA? Just Not True

“The Hill” newspaper recently reported that: “a survey of federal budgets devoted to developing and enforcing regulations found that many agencies will spend more in 2013 and 2014 than in previous years, indicating that the writing and enforcing of new regulations is largely unimpeded by the massive cuts, known as sequestration.” That certainly sounds authoritative…until you look at the analysis. In fact, the report’s authors appear to know nothing about the federal budget and have used inherently unreliable data in calculating FY 13 and FY 14 spending levels. One can only hope that the authors—allegedly academic experts--know more about regulatory policy than they do about federal budgets.




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California Adopts a Bundle of AI & Privacy Laws, Most Controversial Bills Vetoed (Updated)

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Government 'miscommunicated' PPE stock levels to pharmacies during first COVID-19 wave, MPs told

The government implied wholesalers had more personal protective equipment in stock than was the case during the first wave of the COVID-19 pandemic, the Healthcare Distribution Association has said.




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New drug cuts the risk of death in bladder cancer by 30% compared with chemotherapy, study suggests

A new type of drug that targets chemotherapy directly to cancer cells reduces the risk of death from the most common type of bladder cancer by 30%, a phase III trial in the New England Journal of Medicine has suggested.




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IFM’s Hat Trick and Reflections On Option-To-Buy M&A

Today IFM Therapeutics announced the acquisition of IFM Due, one of its subsidiaries, by Novartis. Back in Sept 2019, IFM granted Novartis the right to acquire IFM Due as part of an “option to buy” collaboration around cGAS-STING antagonists for

The post IFM’s Hat Trick and Reflections On Option-To-Buy M&A appeared first on LifeSciVC.




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Boiling It Down: Conveying Complexity For Decision-makers

By Ankit Mahadevia, former CEO of Spero Therapeutics, as part of the From The Trenches feature of LifeSciVC Drug development is complex. So is running a business. Sometimes, the work of doing both can make your head spin. In my

The post Boiling It Down: Conveying Complexity For Decision-makers appeared first on LifeSciVC.




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Keeping It Simple: What Really Matters For Emerging Enterprises  

By Ankit Mahadevia, chairman of Spero Therapeutics, as part of the From The Trenches feature of LifeSciVC A common theme in startup literature is that by cutting a range of unnecessary tasks, a step-change in results will follow.  I’ve found

The post Keeping It Simple: What Really Matters For Emerging Enterprises   appeared first on LifeSciVC.




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Brazen Scofflaws? Are Pharma Companies Really Completely Ignoring FDAAA?

Results reporting requirements are pretty clear. Maybe critics should re-check their methods?

Ben Goldacre has rather famously described the clinical trial reporting requirements in the Food and Drug Administration Amendments Act of 2007 as a “fake fix” that was being thoroughly “ignored” by the pharmaceutical industry.

Pharma: breaking the law in broad daylight?
He makes this sweeping, unconditional proclamation about the industry and its regulators on the basis of  a single study in the BMJ, blithely ignoring the fact that a) the authors of the study admitted that they could not adequately determine the number of studies that were meeting FDAAA requirements and b) a subsequent FDA review that identified only 15 trials potentially out of compliance, out of a pool of thousands.


Despite the fact that the FDA, which has access to more data, says that only a tiny fraction of studies are potentially noncompliant, Goldacre's frequently repeated claims that the law is being ignored seems to have caught on in the general run of journalistic and academic discussions about FDAAA.

And now there appears to be additional support for the idea that a large percentage of studies are noncompliant with FDAAA results reporting requirements, in the form of a new study in the Journal of Clinical Oncology: "Public Availability of Results of Trials Assessing Cancer Drugs in the United States" by Thi-Anh-Hoa Nguyen, et al.. In it, the authors report even lower levels of FDAAA compliance – a mere 20% of randomized clinical trials met requirements of posting results on clinicaltrials.gov within one year.

Unsurprisingly, the JCO results were immediately picked up and circulated uncritically by the usual suspects.

I have to admit not knowing much about pure academic and cooperative group trial operations, but I do know a lot about industry-run trials – simply put, I find the data as presented in the JCO study impossible to believe. Everyone I work with in pharma trials is painfully aware of the regulatory environment they work in. FDAAA compliance is a given, a no-brainer: large internal legal and compliance teams are everywhere, ensuring that the letter of the law is followed in clinical trial conduct. If anything, pharma sponsors are twitchily over-compliant with these kinds of regulations (for example, most still adhere to 100% verification of source documentation – sending monitors to physically examine every single record of every single enrolled patient - even after the FDA explicitly told them they didn't have to).

I realize that’s anecdotal evidence, but when such behavior is so pervasive, it’s difficult to buy into data that says it’s not happening at all. The idea that all pharmaceutical companies are ignoring a highly visible law that’s been on the books for 6 years is extraordinary. Are they really so brazenly breaking the rules? And is FDA abetting them by disseminating incorrect information?

Those are extraordinary claims, and would seem to require extraordinary evidence. The BMJ study had clear limitations that make its implications entirely unclear. Is the JCO article any better?

Some Issues


In fact, there appear to be at least two major issues that may have seriously compromised the JCO findings:

1. Studies that were certified as being eligible for delayed reporting requirements, but do not have their certification date listed.

The study authors make what I believe to be a completely unwarranted assumption:

In trials for approval of new drugs or approval for a new indication, a certification [permitting delayed results reporting] should be posted within 1 year and should be publicly available.

It’s unclear to me why the authors think the certifications “should be” publicly available. In re-reading FDAAA section 801, I don’t see any reference to that being a requirement. I suppose I could have missed it, but the authors provide a citation to a page that clearly does not list any such requirement.

But their methodology assumes that all trials that have a certification will have it posted:

If no results were posted at ClinicalTrials.gov, we determined whether the responsible party submitted a certification. In this case, we recorded the date of submission of the certification to ClinicalTrials.gov.

If a sponsor gets approval from FDA to delay reporting (as is routine for all drugs that are either not approved for any indication, or being studied for a new indication – i.e., the overwhelming majority of pharma drug trials), but doesn't post that approval on the registry, the JCO authors deem that trial “noncompliant”. This is not warranted: the company may have simply chosen not to post the certification despite being entirely FDAAA compliant.

2. Studies that were previously certified for delayed reporting and subsequently reported results

It is hard to tell how the authors treated this rather-substantial category of trials. If a trial was certified for delayed results reporting, but then subsequently published results, the certification date becomes difficult to find. Indeed, it appears in the case where there were results, the authors simply looked at the time from study completion to results posting. In effect, this would re-classify almost every single one of these trials from compliant to non-compliant. Consider this example trial:


  • Phase 3 trial completes January 2010
  • Certification of delayed results obtained December 2010 (compliant)
  • FDA approval June 2013
  • Results posted July 2013 (compliant)


In looking at the JCO paper's methods section, it really appears that this trial would be classified as reporting results 3.5 years after completion, and therefore be considered noncompliant with FDAAA. In fact, this trial is entirely kosher, and would be extremely typical for many phase 2 and 3 trials in industry.

Time for Some Data Transparency


The above two concerns may, in fact, be non-issues. They certainly appear to be implied in the JCO paper, but the wording isn't terribly detailed and could easily be giving me the wrong impression.

However, if either or both of these issues are real, they may affect the vast majority of "noncompliant" trials in this study. Given the fact that most clinical trials are either looking at new drugs, or looking at new indications for new drugs, these two issues may entirely explain the gap between the JCO study and the unequivocal FDA statements that contradict it.

I hope that, given the importance of transparency in research, the authors will be willing to post their data set publicly so that others can review their assumptions and independently verify their conclusions. It would be more than a bit ironic otherwise.

[Image credit: Shamless lawlessness via Flikr user willytronics.]


Thi-Anh-Hoa Nguyen, Agnes Dechartres, Soraya Belgherbi, and Philippe Ravaud (2013). Public Availability of Results of Trials Assessing Cancer Drugs in the United States JOURNAL OF CLINICAL ONCOLOGY DOI: 10.1200/JCO.2012.46.9577




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These Words Have (Temporarily) Relocated

Near the end of last year, I had the bright idea of starting a second blog, Placebo Lead-In, to capture a lot of smaller items that I found interesting but wasn't going to work up into a full-blown, 1000 word post.

According to Murphy’s Law, or the Law of Unintended Consequences, or the Law of Biting Off More Than You Can Chew, or some such similar iron rule of the universe, what happened next should have been predictable.

First, my team at CAHG Trials launched a new blog, First Patient In. FPI is dedicated to an open discussion of patient recruitment ideas, and I’m extremely proud of what we've published so far.

Next, I was invited to be a guest blogger for the upcoming Partnerships in Clinical Trials Conference.

Suddenly, I've gone from 1 blog to 4. And while my writing output appears to have increased, it definitely hasn't quadrupled. So this blog has been quiet for a bit too long as a result.

The good news is that the situation is temporary - Partnerships will actually happen at the end of this month. (If you’re going: drop me a line and let’s meet. If you’re not: you really should come and join us!) My contributions to FPI will settle into a monthly post, as I have a fascinating and clever team to handle most of the content.

In case you've missed it, then, here is a brief summary of my posts elsewhere over the past 2 months.

First Patient In


Partnerships in Clinical Trials



Please take a look, and I will see you back here soon.

[Photo credit: detour sign via Flikr user crossley]




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Retention metrics, simplified

[Originally posted on First Patient In]

In my experience, most clinical trials do not suffer from significant retention issues. This is a testament to the collaborative good will of most patients who consent to participate, and to the patient-first attitude of most research coordinators.

However, in many trials – especially those that last more than a year – the question of whether there is a retention issue will come up at some point while the trial’s still going. This is often associated with a jump in early terminations, which can occur as the first cohort of enrollees has been in the trial for a while.

It’s a good question to ask midstream: are we on course to have as many patients fully complete the trial as we’d originally anticipated?

However, the way we go about answering the question is often flawed and confusing. Here’s an example: a sponsor came to us with what they thought was a higher rate of early terminations than expected. The main problem? They weren't actually sure.

Here’s their data. Can you tell?

Original retention graph. Click to enlarge.
If you can, please let me know how! While this chart is remarkably ... full of numbers, it provides no actual insight into when patients are dropping out, and no way that I can tell to project eventual total retention.

In addition, measuring the “retention rate” as a simple ratio of active to terminated patients will not provide an accurate benchmark until the trial is almost over. Here's why: patients tend to drop out later in a trial, so as long as you’re enrolling new patients, your retention rate will be artificially high. When enrollment ends, your retention rate will appear to drop rapidly – but this is only because of the artificial lift you had earlier.

In fact, that was exactly the problem the sponsor had: when enrollment ended, the retention rate started dropping. It’s good to be concerned, but it’s also important to know how to answer the question.

Fortunately, there is a very simple way to get a clear answer in most cases – one that’s probably already in use by your  biostats team around the corner: the Kaplan-Meier “survival” curve.

Here is the same study data, but patient retention is simply depicted as a K-M graph. The key difference is that instead of calendar dates, we used the relative measure of time in the trial for each patient. That way we can easily spot where the trends are.


In this case, we were able to establish quickly that patient drop-outs were increasing at a relatively small constant rate, with a higher percentage of drops coinciding with the one-year study visit. Most importantly, we were able to very accurately predict the eventual number of patients who would complete the trial. And it only took one graph!







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What does a 2nd Trump term mean for the Affordable Care Act?

President-elect Donald Trump tried unsuccessfully to get rid of the Affordable Care Act during his first term. What action will he take this time around?




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Patrick Dempsey aims to raise awareness of cancer disparities and encourage screening

NPR's Leila Fadel talks with actor Patrick Dempsey about his efforts to raise money for cancer treatment and prevention.




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With Trump coming into power, the NIH is in the crosshairs

The National Institutes of Health, the crown jewel of biomedical research in the U.S., could face big changes under the new Trump administration, some fueled by pandemic-era criticisms of the agency.




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Kumpulan Game Slot Gacor Dengan Persentase RTP Tertinggi Hari Ini

Dalam dunia perjudian online yang terus berkembang, pencarian para pemain untuk menemukan peluang terbaik dalam meraih kemenangan mengarah pada fenomena populer: kumpulan game slot gacor dengan persentase RTP tertinggi hari…

The post Kumpulan Game Slot Gacor Dengan Persentase RTP Tertinggi Hari Ini appeared first on Biosimilarnews.




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Game Slot Gacor Gampang Menang Habanero

Habanero tidak hanya menyajikan game slot biasa, melainkan sebuah petualangan menang tanpa batas. Dengan tema-tema yang beragam, mulai dari petualangan antariksa hingga ke dunia mitologi, setiap game Habanero memiliki keunikan…

The post Game Slot Gacor Gampang Menang Habanero appeared first on Biosimilarnews.




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Link Daftar Situs Slot Gacor Gampang Menang Maxwin Terpercaya Hari Ini

Keuntungan besar dan kegembiraan yang ditawarkan oleh mesin slot online membuatnya semakin populer. Namun, dalam lautan situs slot yang ada, bagaimana Anda bisa menemukan situs slot terbaik yang dapat memberikan…

The post Link Daftar Situs Slot Gacor Gampang Menang Maxwin Terpercaya Hari Ini appeared first on Biosimilarnews.




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Origami Helps Implant Sensors in Bio-Printed Tissue



In the United States alone, more than 100,000 people currently need a lifesaving organ transplant. Instead of waiting for donors, one way to solve this crisis in the future is to assemble replacement organs with bio-printing—3D printing that uses inks containing living cells. Scientists in Israel have found that origami techniques could help fold sensors into bio-printed materials to help determine whether they are behaving safely and properly.

Although bio-printing something as complex as a human organ is still a distant possibility, there are a host of near-term applications for the technique. For example, in drug research, scientists can bio-print living, three-dimensional tissues with which to examine the effects of various compounds.

Ideally, researchers would like to embed sensors within bio-printed items to keep track of how well they are behaving. However, the three-dimensional nature of bio-printed objects makes it difficult to lodge sensors within them in a way that can monitor every part of the structures.

“It will, hopefully in the future, allow us to monitor and assess 3D biostructures before we would like to transplant them.” —Ben Maoz, Tel Aviv University

Now scientists have developed a 3D platform inspired by origami that can help embed sensors in bio-printed objects in precise locations. “It will, hopefully in the future, allow us to monitor and assess 3D biostructures before we would like to transplant them,” says Ben Maoz, a professor of biomedical engineering at Tel Aviv University in Israel.

The new platform is a silicone rubber device that can fold around a bio-printed structure. The prototype holds a commercial array of 3D electrodes to capture electrical signals. It also possesses other electrodes that can measure electrical resistance, which can reveal how permeable cells are to various medications. A custom 3D software model can tailor the design of the origami and all the electrodes so that the sensors can be placed in specific locations in the bio-printed object.

The scientists tested their device on bio-printed clumps of brain cells. The research team also grew a layer of cells onto the origami that mimicked the blood-brain barrier, a cell layer that protects the brain from undesirable substances that the body’s blood might be carrying. By folding this combination of origami and cells onto the bio-printed structures, Maoz and his colleagues were able to monitor neural activity within the brain cells and see how their synthetic blood-brain barrier might interfere with medications intended to treat brain diseases.

Maoz says the new device can incorporate many types of sensors beyond electrodes, such as temperature or acidity sensors. It can also incorporate flowing liquid to supply oxygen and nutrients to cells, the researchers note.

Currently, this device “will mainly be used for research and not for clinical use,” Maoz says. Still, it could “significantly contribute to drug development—assessing drugs that are relevant to the brain.”

The researchers say they can use their origami device with any type of 3D tissue. For example, Maoz says they can use it on bio-printed structures made from patient cells “to help with personalized medicine and drug development.”

The origami platform could also help embed devices that can modify bio-printed objects. For instance, many artificially grown tissues function better if they are placed under the kinds of physical stresses they might normally experience within the body, and the origami platform could integrate gadgets that can exert such mechanical forces on bio-printed structures. “This can assist in accelerating tissue maturation, which might be relevant to clinical applications,” Maoz says.

The scientists detailed their findings in the 26 June issue of Advanced Science.




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Next-Gen Brain Implant Uses a Graphene Chip



A Barcelona-based startup called Inbrain Neuroelectronics has produced a novel brain implant made of graphene and is gearing up for its first in-human test this summer.

The technology is a type of brain-computer interface. BCIs have garnered interest because they record signals from the brain and transmit them to a computer for analysis. They have been used for medical diagnostics, as communication devices for people who can’t speak, and to control external equipment, including robotic limbs. But Inbrain intends to transform its BCI technology into a therapeutic tool for patients with neurological issues such as Parkinson’s disease.

Because Inbrain’s chip is made of graphene, the neural interface has some interesting properties, including the ability to be used to both record from and stimulate the brain. That bidirectionality comes from addressing a key problem with the metallic chips typically used in BCI technology: Faradaic reactions. Faradaic reactions are a particular type of electrochemical processes that occurs between a metal electrode and an electrolyte solution. As it so happens, neural tissue is largely composed of aqueous electrolytes. Over time, these Faradaic reactions reduce the effectiveness of the metallic chips.

That’s why Inbrain replaced the metals typically used in such chips with graphene, a material with great electrical conductivity. “Metals have Faraday reactions that actually make all the electrons interact with each other, degrading their effectiveness...for transmitting signals back to the brain,” said Carolina Aguilar, CEO and cofounder of Inbrain.

Because graphene is essentially carbon and not a metal, Aguilar says the chip can inject 200 times as much charge without creating a Faradic reaction. As a result, the material is stable over the millions of pulses of stimulation required of a therapeutic tool. While Inbrain is not yet testing the chip for brain stimulation, the company expects to reach that goal in due time.

The graphene-based chip is produced on a wafer using traditional semiconductor technology, according to Aguilar. At clean-room facilities, Inbrain fabricates a 10-micrometer-thick chip. The chip consists of what Aguilar terms “graphene dots” (not to be confused with graphene quantum dots) that range in size from 25 to 300 micrometers. “This micrometer scale allows us to get that unique resolution on the decoding of the signals from the brain, and also provides us with the micrometric stimulation or modulation of the brain,” added Aguilar.

Testing the Graphene-Based BCI

The first test of the platform in a human patient will soon be performed at the University of Manchester, in England, where it will serve as an interface during the resection of a brain tumor. When resecting a tumor, surgeons must ensure that they don’t damage areas like the brain’s language centers so the patient isn’t impaired after the surgery. “The chip is positioned during the tumor resection so that it can read, at a very high resolution, the signals that tell the surgeon where there is a tumor and where there is not a tumor,” says Aguilar. That should enable the surgeons to extract the tumor with micrometric precision while preserving functional areas like speech and cognition.

Aguilar added, “We have taken this approach for our first human test because it is a very reliable and quick path to prove the safety of graphene, but also demonstrate the potential of what it can do in comparison to metal technology that is used today.”

Aguilar stresses that the Inbrain team has already tested the graphene-based chip’s biocompatibility. “We have been working for the last three years in biocompatibility through various safety studies in large animals,” said Aguilar. “So now we can have these green lights to prove an additional level of safety with humans.”

While this test of the chip at Manchester is aimed at aiding in brain tumor surgery, the same technology could eventually be used to help Parkinson’s patients. Toward this aim, Inbrain’s system was granted Breakthrough Device Designation last September from the U.S. Food & Drug Administration as an adjunctive therapy for treating Parkinson’s disease. “For Parkinson’s treatment, we have been working on different preclinical studies that have shown reasonable proof of superiority versus current commercial technology in the [reduction] of Parkinson’s disease symptoms,” said Aguilar.

For treating Parkinson’s, Inbrain’s chip connects with the nigrostriatal pathway in the brain that is critical for movements. The chip will first decode the intention message from the brain that triggers a step or the lifting of the arm—something that a typical BCI can do. But Inbrain’s chip, with its micrometric precision, can also decode pathological biomarkers related to Parkinson’s symptoms, such as tremors, rigidity, and freezing of the gait.

By determining these biomarkers with great precision, Inbrain’s technology can determine how well a patient’s current drug regimen is working. In this first iteration of the Inbrain chip, it doesn’t treat the symptoms of Parkinson’s directly, but instead makes it possible to better target and reduce the amount of drugs that are used in treatment.

“Parkinson’s patients take huge amounts of drugs that have to be changed over time just to keep up with the growing resistance patients develop to the power of the drug,” said Aguilar. “We can reduce it at least 50 percent and hopefully in the future more as our devices become precise.”




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Biocompatible Mic Could Lead to Better Cochlear Implants



Cochlear implants—the neural prosthetic cousins of standard hearing aids—can be a tremendous boon for people with profound hearing loss. But many would-be users are turned off by the device’s cumbersome external hardware, which must be worn to process signals passing through the implant. So researchers have been working to make a cochlear implant that sits entirely inside the ear, to restore speech and sound perception without the lifestyle restrictions imposed by current devices.

A new biocompatible microphone offers a bridge to such fully internal cochlear implants. About the size of a grain of rice, the microphone is made from a flexible piezoelectric material that directly measures the sound-induced motion of the eardrum. The tiny microphone’s sensitivity matches that of today’s best external hearing aids.

Cochlear implants create a novel pathway for sounds to reach the brain. An external microphone and processor, worn behind the ear or on the scalp, collect and translate incoming sounds into electrical signals, which get transmitted to an electrode that’s surgically implanted in the cochlea, deep within the inner ear. There, the electrical signals directly stimulate the auditory nerve, sending information to the brain to interpret as sound.

But, says Hideko Heidi Nakajima, an associate professor of otolaryngology at Harvard Medical School and Massachusetts Eye and Ear, “people don’t like the external hardware.” They can’t wear it while sleeping, or while swimming or doing many other forms of exercise, and so many potential candidates forgo the device altogether. What’s more, incoming sound goes directly into the microphone and bypasses the outer ear, which would otherwise perform the key functions of amplifying sound and filtering noise. “Now the big idea is instead to get everything—processor, battery, microphone—inside the ear,” says Nakajima. But even in clinical trials of fully internal designs, the microphone’s sensitivity—or lack thereof—has remained a roadblock.

Nakajima, along with colleagues from MIT, Harvard, and Columbia University, fabricated a cantilever microphone that senses the motion of a bone attached behind the eardrum called the umbo. Sound entering the ear canal causes the umbo to vibrate unidirectionally, with a displacement 10 times as great as other nearby bones. The tip of the “UmboMic” touches the umbo, and the umbo’s movements flex the material and produce an electrical charge through the piezoelectric effect. These electrical signals can then be processed and transmitted to the auditory nerve. “We’re using what nature gave us, which is the outer ear,” says Nakajima.

Why a cochlear implant needs low-noise, low-power electronics

Making a biocompatible microphone that can detect the eardrum’s minuscule movements isn’t easy, however. Jeff Lang, a professor of electrical engineering at MIT who jointly led the work, points out that only certain materials are tolerated by the human body. Another challenge is shielding the device from internal electronics to reduce noise. And then there’s long-term reliability. “We’d like an implant to last for decades,” says Lang.

In tests of the implantable microphone prototype, a laser beam measures the umbo’s motion, which gets transferred to the sensor tip. JEFF LANG & HEIDI NAKAJIMA

The researchers settled on a triangular design for the 3-by-3-millimeter sensor made from two layers of polyvinylidene fluoride (PVDF), a biocompatible piezoelectric polymer, sandwiched between layers of flexible, electrode-patterned polymer. When the cantilever tip bends, one PVDF layer produces a positive charge and the other produces a negative charge—taking the difference between the two cancels much of the noise. The triangular shape provides the most uniform stress distribution within the bending cantilever, maximizing the displacement it can undergo before it breaks. “The sensor can detect sounds below a quiet whisper,” says Lang.

Emma Wawrzynek, a graduate student at MIT, says that working with PVDF is tricky because it loses its piezoelectric properties at high temperatures, and most fabrication techniques involve heating the sample. “That’s a challenge especially for encapsulation,” which involves encasing the device in a protective layer so it can remain safely in the body, she says. The group had success by gradually depositing titanium and gold onto the PVDF while using a heat sink to cool it. That approach created a shielding layer that protects the charge-sensing electrodes from electromagnetic interference.

The other tool for improving a microphone’s performance is, of course, amplifying the signal. “On the electronics side, a low-noise amp is not necessarily a huge challenge to build if you’re willing to spend extra power,” says Lang. But, according to MIT graduate student John Zhang, cochlear implant manufacturers try to limit power for the entire device to 5 milliwatts, and just 1 mW for the microphone. “The trade-off between noise and power is hard to hit,” Zhang says. He and fellow student Aaron Yeiser developed a custom low-noise, low-power charge amplifier that outperformed commercially available options.

“Our goal was to perform better than or at least equal the performance of high-end capacitative external microphones,” says Nakajima. For leading external hearing-aid microphones, that means sensitivity down to a sound pressure level of 30 decibels—the equivalent of a whisper. In tests of the UmboMic on human cadavers, the researchers implanted the microphone and amplifier near the umbo, input sound through the ear canal, and measured what got sensed. Their device reached 30 decibels over the frequency range from 100 hertz to 6 kilohertz, which is the standard for cochlear implants and hearing aids and covers the frequencies of human speech. “But adding the outer ear’s filtering effects means we’re doing better [than traditional hearing aids], down to 10 dB, especially in speech frequencies,” says Nakajima.

Plenty of testing lies ahead, at the bench and on sheep before an eventual human trial. But if their UmboMic passes muster, the team hopes that it will help more than 1 million people worldwide go about their lives with a new sense of sound.

The work was published on 27 June in the Journal of Micromechanics and Microengineering.




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