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Minuscule robots for targeted drug delivery December 11, 2024 California Institute of Technology An interdisciplinary team has created tiny bubble-like microrobots that can deliver therapeutics right where they are needed and then be absorbed by the body. Facebook Twitter Pinterest LinkedIN Email In the future, delivering therapeutic drugs exactly where they are needed within the body could be the task of miniature robots. Not little metal humanoid or even bio-mimicking robots; think instead of tiny bubble-like spheres. Such robots would have a long and challenging list of requirements. For example, they would need to survive in bodily fluids, such as stomach acids, and be controllable, so they could be directed precisely to targeted sites. They also must release their medical cargo only when they reach their target, and then be absorbable by the body without causing harm. Now, microrobots that tick all those boxes have been developed by a Caltech-led team. Using the bots, the team successfully delivered therapeutics that decreased the size of bladder tumors in mice. A paper describing the work appears in the journal Science Robotics . "We have designed a single platform that can address all of these problems," says Wei Gao, professor of medical engineering at Caltech, Heritage Medical Research Institute Investigator, and co-corresponding author of the new paper about the bots, which the team calls bioresorbable acoustic microrobots (BAM). "Rather than putting a drug into the body and letting it diffuse everywhere, now we can guide our microrobots directly to a tumor site and release the drug in a controlled and efficient way," Gao says. The concept of micro- or nanorobots is not new. People have been developing versions of these over the past two decades. However, thus far, their applications in living systems have been limited because it is extremely challenging to move objects with precision in complex biofluids such as blood, urine, or saliva, Gao says. The robots also have to be biocompatible and bioresorbable, meaning that they leave nothing toxic behind in the body. The Caltech-developed microrobots are spherical microstructures made of a hydrogel called poly(ethylene glycol) diacrylate. Hydrogels are materials that start out in liquid or resin form and become solid when the network of polymers found within them becomes cross-linked, or hardens. This structure and composition enable hydrogels to retain large amounts of fluid, making many of them biocompatible. The additive manufacturing fabrication method also enables the outer sphere to carry the therapeutic cargo to a target site within the body. To develop the hydrogel recipe and to make the microstructures, Gao turned to Caltech's Julia R. Greer, the Ruben F. and Donna Mettler Professor of Materials Science, Mechanics and Medical Engineering, the Fletcher Jones Foundation Director of the Kavli Nanoscience Institute, and co-corresponding author of the paper. Greer's group has expertise in two-photon polymerization (TPP) lithography, a technique that uses extremely fast pulses of infrared laser light to selectively cross-link photosensitive polymers according to a particular pattern in a very precise manner. The technique allows a structure to be built up layer by layer, in a way reminiscent of 3D printers, but in this case, with much greater precision and form complexity. Greer's group managed to "write," or print out, microstructures that are roughly 30 microns in diameter -- about the diameter of a human hair. "This particular shape, this sphere, is very complicated to write," Greer says. "You have to know certain tricks of the trade to keep the spheres from collapsing on themselves. We were able to not only synthesize the resin that contains all the biofunctionalization and all the medically necessary elements, but we were able to write them in a precise spherical shape with the necessary cavity." In their final form, the microrobots incorporate magnetic nanoparticles and the therapeutic drug within the outer structure of the spheres. The magnetic nanoparticles allow the scientists to direct the robots to a desired location using an external magnetic field. When the robots reach their target, they remain in that spot, and the drug passively diffuses out. Gao and colleagues designed the exterior of the microstructure to be hydrophilic -- that is, attracted to water -- which ensures that the individual robots do not clump together as they travel through the body. However, the inner surface of the microrobot cannot be hydrophilic because it needs to trap an air bubble, and bubbles are easy to collapse or dissolve. To construct hybrid microrobots that are both hydrophilic on their exterior and hydrophobic, or repellent to water, in their interior, the researchers devised a two-step chemical modification. First, they attached long-chain carbon molecules to the hydrogel, making the entire structure hydrophobic. Then the researchers used a technique called oxygen plasma etching to remove some of those long-chain carbon structures from the interior, leaving the outside hydrophobic and the interior hydrophilic. "This was one of the key innovations of this project," says Gao, who is also a Ronald and JoAnne Willens Scholar. "This asymmetric surface modification, where the inside is hydrophobic and the outside is hydrophilic, really allows us to use many robots and still trap bubbles for a prolonged period of time in biofluids, such as urine or serum." Indeed, the team showed that the bubbles can last for as long as several days with this treatment versus the few minutes that would otherwise be possible. The presence of trapped bubbles is also crucial for moving the robots and for keeping track of them with real-time imaging. For example, to enable propulsion, the team designed the microrobot sphere to have two cylinder-like openings -- one at the top and another to one side. When the robots are exposed to an ultrasound field, the bubbles vibrate, causing the surrounding fluid to stream away from the robots through the opening, propelling the robots through the fluid. Gao's team found that the use of two openings gave the robots the ability to move not only in various viscous biofluids, but also at greater speeds than can be achieved with a single opening. Trapped within each microstructure is an egg-like bubble that serves as an excellent ultrasound imaging contrast agent, enabling real-time monitoring of the bots in vivo . The team developed a way to track the microrobots as they move to their targets with the help of ultrasound imaging experts Mikhail Shapiro, Caltech's Max Delbruck Professor of Chemical Engineering and Medical Engineering, a Howard Hughes Medical Institute Investigator; co-corresponding author Di Wu, research scientist and director of the DeepMIC Center at Caltech; and co-corresponding author Qifa Zhou, professor of ophthalmology and biomedical engineering at USC. The final stage of development involved testing the microrobots as a drug-delivery tool in mice with bladder tumors. The researchers found that four deliveries of therapeutics provided by the microrobots over the course of 21 days was more effective at shrinking tumors than a therapeutic not delivered by robots. "We think this is a very promising platform for drug delivery and precision surgery," Gao says. "Looking to the future, we could evaluate using this robot as a platform to deliver different types of therapeutic payloads or agents for different conditions. And in the long term, we hope to test this in humans." The work was supported by the Kavli Nanoscience Institute at Caltech as well as by funding from the National Science Foundation; the Heritage Medical Research Institute; the Singapore Ministry of Education Academic Research Fund; the National Institutes of Health; the Army Research Office through the Institute for Collaborative Biotechnologies; the Caltech DeepMIC Center, with support of the Caltech Beckman Institute and the Arnold and Mabel Beckman Foundation; and the David and Lucile Packard Foundation. Story Source: Materials provided by California Institute of Technology . Original written by Kimm Fesenmaier. Note: Content may be edited for style and length. Related Multimedia : Journal Reference : Cite This Page :www.nuebe888.com 。

On Mahayuti Win, Sharad Pawar Credits These 2 Major Factors, Defends Yugendra Vs Ajit Contest In BaramatiSouth Korea's leader prompts dismay by briefly declaring martial law. Here's what to know

Let change come organically, not by force I have read with interest the various pieces about why Kamala Harris lost this last election in such a decisive manner. Not a landslide by any means, but a decisive loss nonetheless. The rhetorical contortions are nothing short of amazing. She lost for the simple reason that she was an inauthentic, dishonest shill for the progressive left. No one was buying what she was selling. In today’s political landscape, each party pretty much owns its base. What a 45/45 split? Sadly it only about 10% actually decide the vote. The main issue before the people was the progressives obsession with forced social change. We as a society are based on the Judeo-Christian concept. With all the baggage and benefits derived therein. That is a simple fact. The drive to force such radical change so fast was their downfall. Let change come organically. Likely most people don’t have have serious issues with the personal choice of other people. But the aggressive nature of the progressive social warriors and their media allies has probably caused more harm than good to their cause. Let the change come organically. No one wants it forced down their throats. Karl Kunkel, Bloomington Labels divide us It’s now been a month since our national, state and local elections. In reflecting back over the last several months, it seems there was more “name calling” than ever before. There was clearly a lack of respect and simple courtesy to one another. Also, it was evident that we are now using more “labels” on ourselves and others than ever before. In prior generations, the labels often focused on race, gender and our Republican and Democrat political parties. Undoubtedly, some of this individuality has been our own creation, but nothing is wrong with this. The label that really intrigues me is that each generation/decade now needs their own label of x, y, z. The days of young and old have become history. My point in writing this letter is to raise the question of whether all these labels being created are more harmful than helpful. It sure appears that we use more and more labels when we talk about each other. I wonder whether we can all tone down the talk of differences and simply focus on a respect and acceptance for each other. It’s simply showing courtesy to one other. Can we give it a try and eliminate the labels that divide us? Jim Fruin, Bloomington A president-elect without integrity, empathy Once again our nation has chosen a president who chooses to have no integrity or empathy. This is what we have chosen to be not only our leader but also the leader of the free world. All the best to everyone! Randy Rasse, Minier What does CIRA’s future hold? I am writing this letter concerning a lack of flight options at the Bloomington-Normal airport. Why does the Peoria airport offer more destinations than CIRA? It would appear that Bloomington-Normal demographics out perform Peoria in population and job growth. Peoria has 40 daily flight departures and we have 7. I believe its time to hear from the CIRA airport board on exactly what is the goal and future of this beautiful underutilized airport to the citizens of this and surrounding communities is and what can be done to put CIRA back on the fast track as it once was. Robert Vericella, Bloomington Catch the latest in Opinion Get opinion pieces, letters and editorials sent directly to your inbox weekly!

Nantes loses 2-0 at home to Le Havre in a match interrupted by angry fans. Lille beats Rennes

Real vs. fake: Can you spot AI-generated images?The Edmonton Oilers made a preventable mistake when they lost forward prospect Raphael Lavoie on waivers to the Vegas Golden Knights, but based on Lavoie now being healthy scratched in the AHL, it turned out to be no major loss for the Oilers. Lavoie has been healthy scratched for the last three games for Henderson Silver Knights in the AHL. In the 11 games that Lavoie's played, he's produced subpar results. Lavoie has only 1 goal, 2 points, and a -9 on ice rating. The Edmonton Oilers selected Raphael Lavoie in the second round of the 2019 draft, and the winger spent 4 seasons developing in the Oilers organization. With the Bakersfield Condors, Lavoie was a skilled offensive player, and grew to be ranked as high as the 7th best Oilers prospect in the offseason. In 66 games with the Condors last year, Lavoie scored an impressive 28 goals and 50 points, and had similar production the year before. Plenty of Oilers analysts suggested he has the talent and the history to make the jump to the NHL, but given his performance so far this year, he's taken a big step back from that goal. Even if that's the case, the Oilers had extremely poor asset management to lose Lavoie for nothing on waivers. Oilers analysts had been warning to trade Lavoie, because losing him on waivers was bound to happen . Lavoie simply had no path to the NHL this season, being blocked by the Oilers surplus of veteran wingers. The Oilers showed they wanted to keep Lavoie when they claimed him back on waivers , but the reality was there was no way for Edmonton to sneak him back to the AHL. Edmonton should've traded Lavoie in the offseason when he had value as a prospect, and they knew that he had no chance to make the team. It's brutal to say, but it'll make Oilers fans feel better to know that he isn't looking like a rising star for a division rival in the Vegas Golden Knights . He'll need to be a lot better with his new team to ever sniff the NHL again. This article first appeared on Oilers Daily and was syndicated with permission.

Musk, an early OpenAI investor and board member, sued the artificial intelligence company earlier this year alleging it had betrayed its founding aims as a nonprofit research lab benefiting the public good rather than pursuing profits. Musk has since escalated the dispute, adding new claims and asking for a court order that would stop OpenAI’s plans to convert itself into a for-profit business more fully. The world's richest man, whose companies include Tesla, SpaceX and social media platform X, last year started his own rival AI company, xAI. Musk says it faces unfair competition from OpenAI and its close business partner Microsoft, which has supplied the huge computing resources needed to build AI systems such as ChatGPT. “OpenAI and Microsoft together exploiting Musk’s donations so they can build a for-profit monopoly, one now specifically targeting xAI, is just too much,” says Musk's filing that alleges the companies are violating the terms of Musk’s foundational contributions to the charity. OpenAI is filing a response Friday opposing Musk’s requested order, saying it would cripple OpenAI’s business and mission to the advantage of Musk and his own AI company. A hearing is set for January before U.S. District Judge Yvonne Gonzalez Rogers in Oakland. At the heart of the dispute is a 2017 internal power struggle at the fledgling startup that led to Altman becoming OpenAI's CEO. Musk also sought to be CEO and in an email outlined a plan where he would “unequivocally have initial control of the company” but said that would be temporary. He grew frustrated after two other OpenAI co-founders said he would hold too much power as a major shareholder and chief executive if the startup succeeded in its goal to achieve better-than-human AI known as artificial general intelligence , or AGI. Musk has long voiced concerns about how advanced forms of AI could threaten humanity. “The current structure provides you with a path where you end up with unilateral absolute control over the AGI," said a 2017 email to Musk from co-founders Ilya Sutskever and Greg Brockman. “You stated that you don't want to control the final AGI, but during this negotiation, you've shown to us that absolute control is extremely important to you.” In the same email, titled “Honest Thoughts,” Sutskever and Brockman also voiced concerns about Altman's desire to be CEO and whether he was motivated by “political goals.” Altman eventually succeeded in becoming CEO, and has remained so except for a period last year when he was fired and then reinstated days later after the board that ousted him was replaced. OpenAI published the messages Friday in a blog post meant to show its side of the story, particularly Musk's early support for the idea of making OpenAI a for-profit business so it could raise money for the hardware and computer power that AI needs. It was Musk, through his wealth manager Jared Birchall, who first registered “Open Artificial Technologies Technologies, Inc.”, a public benefit corporation, in September 2017. Then came the “Honest Thoughts” email that Musk described as the “final straw.” “Either go do something on your own or continue with OpenAI as a nonprofit,” Musk wrote back. OpenAI said Musk later proposed merging the startup into Tesla before resigning as the co-chair of OpenAI's board in early 2018. Musk didn't immediately respond to emailed requests for comment sent to his companies Friday. Asked about his frayed relationship with Musk at a New York Times conference last week, Altman said he felt “tremendously sad” but also characterized Musk’s legal fight as one about business competition. “He’s a competitor and we’re doing well,” Altman said. He also said at the conference that he is “not that worried” about the Tesla CEO’s influence with President-elect Donald Trump. OpenAI said Friday that Altman plans to make a $1 million personal donation to Trump’s inauguration fund, joining a number of tech companies and executives who are working to improve their relationships with the incoming administration.IN RECENT years, global attention has increasingly shifted towards South-east Asia, with many analysts acknowledging the Association of Southeast Asian Nations (Asean) as a rising force on the global stage. Often described as an underdog in geopolitics and economics, Asean’s emergence may seem understated, but its influence is growing rapidly. This bloc of 10 member states – Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, the Philippines, Singapore, Thailand and Vietnam – has proven itself to be a critical player in shaping regional stability, economic growth and diplomatic dialogue. With a combined population of over 680 million and a collective gross domestic product exceeding US$3 trillion, Asean is positioning itself as a key actor in the global balance of power. One of the defining features of Asean’s emergence as a global player is its robust economic growth. The region has seen consistent GDP growth rates of around 5 per cent annually over the past two decades, outpacing many other parts of the world. Asean’s diverse economies, ranging from the highly developed financial hub of Singapore to the rapidly industrialising Vietnam and Indonesia, offer a mix of opportunities for investors and businesses alike. Foreign direct investment (FDI) into the region has surged, with Asean attracting more than US$174 billion in 2022 alone. Much of this growth is linked to Asean’s strategic location along vital global trade routes, as well as the region’s relatively low labour costs and improving infrastructure. Its economic policies, particularly efforts to reduce tariffs and streamline regulatory frameworks, have made it a magnet for businesses seeking to tap a young and growing consumer base. Furthermore, Asean’s youthful and growing population presents a significant market opportunity. With a median age of just 29.8 years, Asean’s demographic advantage contrasts sharply with the ageing populations of developed economies such as Japan and much of Europe. This young population fuels domestic demand for consumer goods, technology, and services, positioning Asean as an increasingly important consumption hub. The pathway for Asean to become an economic powerhouse is closely linked to its role in global supply chains. As companies seek to diversify their production bases, the region has emerged as an alternative hub for manufacturing and assembly, particularly in industries such as electronics, textiles, and automotive. The trend has accelerated with the “China-plus-one” strategy, where multinational firms aim to reduce their over-reliance on China by expanding production to nearby countries. Vietnam, for example, has become a major centre for electronics manufacturing, attracting investment from global giants such as Samsung and Apple. Indonesia and Malaysia, with their large domestic markets and resource-rich economies, have also seen a surge in manufacturing investments. Asean’s favourable demographics, competitive labour costs, and improving infrastructure have made it an ideal location for companies looking to ensure resilience and flexibility in their global supply chains. In addition to manufacturing, Asean’s strategic location along vital maritime routes, including the Straits of Malacca, has established it as a critical hub for global trade. Its connectivity between East Asia, South Asia, and beyond enhances its role as a vital conduit for goods and services. Major ports in Singapore, Malaysia and Thailand continue to expand their capacities to serve as key links in the global logistics network. One of Asean’s most promising growth drivers is its commitment to digital transformation. The region’s digital economy is expected to exceed US$300 billion by 2025, driven by increased Internet penetration, a growing middle class, and a young, tech-savvy population. E-commerce, fintech and digital services are booming across Asean, with platforms such as Grab, Gojek and Shopee leading the way in transforming how people shop, pay, and commute. Governments across the region are investing heavily in digital infrastructure, such as 5G networks and smart cities, to support this growth. These investments are aimed at ensuring that Asean remains competitive in the global digital economy and can attract more investment from technology companies. The digital transformation also extends to industries such as manufacturing, logistics, and finance. The adoption of technologies such as artificial intelligence, blockchain, and the Internet of Things is helping Asean companies streamline their operations and integrate more efficiently into global supply chains. This ongoing digital shift will likely propel Asean to the forefront of the Fourth Industrial Revolution, further solidifying its role as a global economic powerhouse. Asean markets vary greatly in size, growth prospects and industries. Thailand and Malaysia have ageing populations, while the Philippines and Indonesia have younger demographics. This diversity means different services are needed in each country. In the Philippines and Indonesia, trade modernisation is key, whereas Thailand focuses on services for an ageing population. Younger, lower GDP markets will see some premiumisation, where brand power and local competition are crucial. The question for active investors is how to best capture this diversity and structural tailwinds via the equity markets. Whereas the populations are large, the stock markets are relatively small both in terms of the number of listed companies and their liquidity. That said, the markets are rich in opportunities for stock pickers as there is a high dispersion of returns across and within countries. It pays to be selective. Typically, our favoured way of investing in these markets is via the banks which provide direct exposure to the economic and demographic trends outlined above. In contrast to many of their global peers, Asean banks, most notably in Indonesia and Philippines, are high return on equity, high growth companies. We also find opportunities in some of the more established, lower growth sectors such as telecoms and property, where a benign competitive landscape allied to a focus on free cash flow rather than capex has seen profitability inflect. In more mature markets such as Thailand, we see opportunities via industries such as healthcare and logistics which are well placed to capture medical tourism and FDI trends respectively. At an aggregate level we have a positive view on the region. Valuations are attractive relative to history and the US Federal Reserve’s rate cuts give central banks across the region the flexibility to cut rates to underpin economic growth rather than keep rates high to defend their currencies. Asean’s rise as an “emerging force” on the global stage is no longer a matter of speculation; it is a reality. With its economic dynamism, strategic location, and diplomatic agility, Asean has transformed itself from a regional bloc focused on peace and stability into a global player with growing influence. However, the road ahead is not without challenges. Political divisions, economic inequality and regional security concerns will test Asean’s unity and resilience. Yet, if the bloc continues to navigate these challenges as skilfully as it has in the past, it stands poised to be a central actor in shaping the future of global geopolitics and economics. Emerging markets are less established than developed markets and therefore involve higher risks. The writer is portfolio manager in the equity division and lead portfolio manager for the Asia ex-Japan equity strategy at T Rowe Price.

Commercial Turf Equipment Set For Strong Growth Reaching $8.12 Billion At A CAGR Of 5.6% By 2028Saudi Arabia banned film for 35 years. The Red Sea festival is just one sign of the industry's rise

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