The new diagnostic is based on nanosensors that can be delivered by an inhaler or a nebulizer. If the sensors encounter cancer-linked proteins in the lungs, they produce a signal that accumulates in the urine, where it can be detected with a simple paper test strip.

This approach could potentially replace or supplement the current gold standard for diagnosing lung cancer, low-dose computed tomography (CT). It could have an especially significant impact in low- and middle-income countries that don’t have widespread availability of CT scanners, the researchers say.

“Around the world, cancer is going to become more and more prevalent in low- and middle-income countries. The epidemiology of lung cancer globally is that it’s driven by pollution and smoking, so we know that those are settings where accessibility to this kind of technology could have a big impact,” says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and of Electrical Engineering and Computer Science at MIT, and a member of MIT’s Koch Institute for Integrative Cancer Research and the Institute for Medical Engineering and Science.

Bhatia is the senior author of the paper, which appears today in Science Advances. Qian Zhong, an MIT research scientist, and Edward Tan, a former MIT postdoc, are the lead authors of the study.

Inhalable particles

To help diagnose lung cancer as early as possible, the U.S. Preventive Services Task Force recommends that heavy smokers over the age of 50 undergo annual CT scans. However, not everyone in this target group receives these scans, and the high false-positive rate of the scans can lead to unnecessary, invasive tests.

Bhatia has spent the last decade developing nanosensors for use in diagnosing cancer and other diseases, and in this study, she and her colleagues explored the possibility of using them as a more accessible alternative to CT screening for lung cancer.

These sensors consist of polymer nanoparticles coated with a reporter, such as a DNA barcode, that is cleaved from the particle when the sensor encounters enzymes called proteases, which are often overactive in tumors. Those reporters eventually accumulate in the urine and are excreted from the body.

Previous versions of the sensors, which targeted other cancer sites such as the liver and ovaries, were designed to be given intravenously. For lung cancer diagnosis, the researchers wanted to create a version that could be inhaled, which could make it easier to deploy in lower resource settings.

“When we developed this technology, our goal was to provide a method that can detect cancer with high specificity and sensitivity, and also lower the threshold for accessibility, so that hopefully we can improve the resource disparity and inequity in early detection of lung cancer,” Zhong says.

To achieve that, the researchers created two formulations of their particles: a solution that can be aerosolized and delivered with a nebulizer, and a dry powder that can be delivered using an inhaler.

Once the particles reach the lungs, they are absorbed into the tissue, where they encounter any proteases that may be present. Human cells can express hundreds of different proteases, and some of them are overactive in tumors, where they help cancer cells to escape their original locations by cutting through proteins of the extracellular matrix. These cancerous proteases cleave DNA barcodes from the sensors, allowing the barcodes to circulate in the bloodstream until they are excreted in the urine.

In the earlier versions of this technology, the researchers used mass spectrometry to analyze the urine sample and detect DNA barcodes. However, mass spectrometry requires equipment that might not be available in low-resource areas, so for this version, the researchers created a lateral flow assay, which allows the barcodes to be detected using a paper test strip.

The researchers designed the strip to detect up to four different DNA barcodes, each of which indicates the presence of a different protease. No pre-treatment or processing of the urine sample is required, and the results can be read about 20 minutes after the sample is obtained.

“We were really pushing this assay to be point-of-care available in a low-resource setting, so the idea was to not do any sample processing, not do any amplification, just to be able to put the sample right on the paper and read it out in 20 minutes,” Bhatia says.

Accurate diagnosis

The researchers tested their diagnostic system in mice that are genetically engineered to develop lung tumors similar to those seen in humans. The sensors were administered 7.5 weeks after the tumors started to form, a time point that would likely correlate with stage 1 or 2 cancer in humans.

In their first set of experiments in the mice, the researchers measured the levels of 20 different sensors designed to detect different proteases. Using a machine learning algorithm to analyze those results, the researchers identified a combination of just four sensors that was predicted to give accurate diagnostic results. They then tested that combination in the mouse model and found that it could accurately detect early-stage lung tumors.

For use in humans, it’s possible that more sensors might be needed to make an accurate diagnosis, but that could be achieved by using multiple paper strips, each of which detects four different DNA barcodes, the researchers say.

The researchers now plan to analyze human biopsy samples to see if the sensor panels they are using would also work to detect human cancers. In the longer term, they hope to perform clinical trials in human patients. A company called Sunbird Bio has already run phase 1 trials on a similar sensor developed by Bhatia’s lab, for use in diagnosing liver cancer and a form of hepatitis known as nonalcoholic steatohepatitis (NASH).

In parts of the world where there is limited access to CT scanning, this technology could offer a dramatic improvement in lung cancer screening, especially since the results can be obtained during a single visit.

“The idea would be you come in and then you get an answer about whether you need a follow-up test or not, and we could get patients who have early lesions into the system so that they could get curative surgery or lifesaving medicines,” Bhatia says.

The research was funded by the Johnson & Johnson Lung Cancer Initiative, the Howard Hughes Medical Institute, the Koch Institute Support (core) Grant from the National Cancer Institute, and the National Institute of Environmental Health Sciences.

A collaborative research team led by Professor Sung-Min Park from the Departments of Convergence IT Engineering, Mechanical Engineering, and Electrical Engineering, and the School of Interdisciplinary Bioscience and Bioengineering at POSTECH, alongside Jiho Lee, enrolled in the MS/Ph.D. program, and Professor Sang-Woo Kim from Yonsei University’s Department of Materials Science and Engineering, together with Dr. Young-Jun Kim and MS/Ph.D. student Joon-Ha Hwang from Sungkyunkwan University, has achieved a groundbreaking development. They’ve created electrostatic materials that function even with extremely weak ultrasound, heralding the era of permanent implantable electronic devices in biomedicine. This research has been published in the international academic journal Advanced Materials.

Patients with implanted devices need to undergo periodic surgeries for battery replacement. This process carries a significant risk of complications and imposes both economic and physical burdens on patients. Recent research explores implantable medical devices that operate wirelessly, yet finding a safe energy source and protective materials remains challenging. Presently, titanium (Ti) is used due to its biocompatibility and durability. However, radio waves cannot pass through this metal, necessitating a separate antenna for wireless power transmission. Consequently, this enlarges the device size, creating more discomfort for patients.

The research team addresses this issue by opting for ultrasound, a safety-validated method in various medical fields for diagnoses and treatments, instead of radio waves. They developed an electrostatic material capable of responding to weak ultrasound by utilizing a composite of high dielectric polymers (P(VDF-TrFE)) and a high dielectric constant ceramic material known as calcium copper titanate (CCTO, CaCu₃Ti₄O₁₂). This material generates static electricity through friction between its material layers, producing effective electrical energy, and possesses an extremely low output impedence, facilitating efficient transmission of the generated electricity.

Using this technology, the research team created an implantable neurological stimulator powered by ultrasound-based energy transmission, eliminating the need for batteries. This was confirmed through experimental validation. In animal model trials, the device was activated even at standard imaging ultrasound levels (500 mW/cm²), imposing minimal strain on the human body. Furthermore, it effectively mitigated symptoms related to abnormal urination caused by overactive bladder disorders through nerve stimulation.

Professor Sung-Min Park stated: “We have addressed the challenges in the field of implantable medical devices using ultrasound-based energy transmission technology that is harmless to the human body. This research serves as a case of introducing advanced material technology into medical devices, and we anticipate that it will promote the emergence of a next-generation medical industry, including the treatment of intractable diseases using implantable devices.”

Professor Sang-Woo Kim remarked: “Devices manufactured based on highly biocompatible materials exhibit excellent mechanical and chemical stability, making them suitable for treating various diseases requiring long-term therapy. Non-battery, miniaturized components with established long-term stability are expected to bring forth new innovations in the market of human-insertable medical devices.”

The research was conducted with support from the Research Leader Program, Pioneer Program of Future Technology, and Bio & Medical Technology Development Program by the National Research Foundation of Korea and the Ministry of Science and ICT, along with Yonsei Fellowship.

“We found three walls of a monumental structure that evidence suggests belonged to a Roman temple that dates to Constantine’s period,” Boin said. “It dates to the fourth century AD and it would be a remarkable addition to the landscape of this corner of Italy. It will significantly aid in the understanding of the ancient town, the ancient townscape and city society in the later Roman Empire because it shows the continuities between the classical pagan world and early Christian Roman world that often get blurred out or written out of the sweeping historical narratives.”

Boin and his excavation team made the monumental discovery over the summer. Boin, an expert in ancient Roman and its religious transitions, had been digging in the town of Spello, the famous medieval hilltop city about 20 minutes from Assisi and 2.5 hours north of Rome. Boin selected the town based on a rescript of a 4th century letter from Emperor Constantine to the townspeople regarding a religious holiday.

This rescript, which was discovered in the 18th century, allowed the people of Spello to celebrate a religious festival in their hometown rather than travel a great distance to another festival. However, in order to do so, the town was told it must erect a temple to Constantine’s divine ancestors, the Flavian family, and worship them, showcasing how multicultural Roman society was at the time.

“There was a remarkable religious continuity between the Roman world and the early Christian world,” Boin said. “Things didn’t change overnight. Before our find, we never had a sense that there were actual physical, religious sites associated with this late ‘imperial cult practice.’ But because of the inscription and its reference to a temple, Spello offered a very tantalizing potential for a major discovery of an Imperial cult underneath a Christian ruler.”

Boin traveled to Spello and oversaw underground imaging to determine if there were any potential ruins below the surface that needed to be uncovered. After many weeks, and almost by chance, Boin finally received promising images underneath a parking lot where the temple was suspected to be.

Very carefully, the team dug into the ground until they found two adjoining walls. More digging unearthed what Boin believes to be the inside walls of the temple. This temple immediately became what Boin calls the largest evidence ever of the Imperial Cult in both fourth-century Italy and the late Roman Empire..

“There’s evidence from other places throughout the Roman world that Christian rulers supported imperial cult practices,” Boin said. “We’ve known that pagans worshiped at their temples in the fourth century, but those findings have all been small and inconsequential. And we’ve known that Christians supported the imperial cult, and we’ve known that without any sense of where it would have happened. This temple bridges those two landmarks, and in that respect, it is unlike any temple that I know about from the Mediterranean world of the fourth century Roman Empire. Any study of the imperial cult in the fourth century Roman Empire is now going to have to take account of this temple, which is an incredible discovery to make.”

With the discovery, Boin now can show how the societal changes of the time moved very slowly. Though Constantine was the first Roman emperor to famously convert to Christianity, it would take almost 70 years for Christianity to become the official religion of the Roman Empire, under the Emperor Theodosius. During that time it still took many convincing and gradual shifts for those who worshiped pagan gods to convert to Christianity.

“This changes everything about how we perceive the pace of social change and our impression of the impact of social and cultural change,” Boin said. “This building, in a very radical way on its own, shows us the staying power of the pagan traditions that had been on the ground for centuries prior to the rise of Christianity, and it shows us how the Roman emperors continued to negotiate their own values, their own hopes and dreams for the future of the emperor and the Empire without knocking down or burying the past.”

Boin and his team will return to Spello next summer to completely excavate the area to examine the full temple, where he hopes to make even more significant discoveries.

“We are on the cusp of giving people a very visible piece of evidence that really upends the neat and tidy ways people think about big moments of cultural change,” Boin said “Cultural changes are never as big as we think they are when living through them, and there’s a lot of gray area in between people’s customs and the broader society and culture. And a lot of those can be left out of the story. So to have this temple potentially be a temple dedicated to Constantice’s divine ancestors as a way to worship the emperor in an increasingly Christian world at the time, it’s so weird and I love that we can bring it to light.”

A research team led by Professor Jonghun Kam and PhD candidate Kwang-Hun Lee from the Division of Environmental Science and Engineering at Pohang University of Science and Technology (POSTECH), has implemented an advanced technique employing an uncrewed surface vehicle to concurrently assess the reservoir water depths and nitrate (NO₃^–) concentrations from the reservoir water surface. The findings from their research were featured in Water Resources Research, an international journal dedicated to the water environment.

Monitoring available water quantity and quality uses indicators such as water depth and nitrate concentration. Nitrates, originating from atmospheric and soil nutrients, enter streams through various pathways, posing a potential threat to aquatic ecosystems and biodiversity when their levels become excessive. Fluctuation of precipitation and water usage further impact water quality, and rising water temperatures contribute to decreased dissolved oxygen, resulting in diminished water quality.

Effective management of water resources requires the dual monitoring of nitrate concentration and water depth. However, these measurements can vary significantly based on the timing and location of assessment. Traditional water depth measurement, typically taken at a single point, introduces uncertainty in estimating the total reservoir water volume. In recent times, uncrewed devices or instruments have been introduced to address this challenge, yet simultaneous measurement of nitrate concentration and water depth has proven challenging.

The research team has achieved the simultaneous measurement of nitrate concentration and water depth using an uncrewed surface vehicle. Over the course of a year, starting in 2021, an uncrewed boat equipped with electrochemical sensors and acoustic doppler current profile sensors was employed to gauge nitrate concentration and water depth in a reservoir (Daljeonji) in Pohang, North Gyeongsang Province in South Korea. The 30 measurements revealed seasonal variations with nitrate levels ranging from 1 ton to 4 tons. Following intense rainfall, the observed nitrate amount was up to 17% lower than previous readings due to rapid water expansion. This underscores the importance of considering timing and weather conditions in water quality assessments, as measurements may lead to over- or underestimation.

Furthermore, the team successfully generated a high-resolution map illustrating the cumulative nitrate content in Daljeonji Reservior based on data collected by the uncrewed surface vehicle. Despite a one-year measurement period and the study’s confinement to Pohang, its significance lies in the independent development of technology capable of simultaneous measurement of nitrate concentration and water depth.

Professor Jonghun Kam who led the research explained, “Our study has outlined both the possibilities and constraints of employing uncrewed robotics in water environment research.” He added, “It is envisioned that this research will provide a guiding framework for the development of the next generation of the Korean national water resources management system, leveraging advanced technologies like uncrewed aerial vehicles to enhance prediction accuracy and optimize water management.”

The study was conducted with the support from the Group Research in Science and Engineering Program and the Ocean, Land, and Atmosphere Carbon Cycle System Research Program of the Ministry of Science and ICT and the National Research Foundation of Korea (2021M3I6A1086808).

According to research conducted by a team of researchers including Professor Kitack Lee from the Division of Environmental Science & Engineering at Pohang University of Science and Technology (POSTECH), and Professor Tongsup Lee and So-Yun Kim from the Department of Oceanography at Pusan National University, the cold atmosphere in the Arctic is influencing the absorption of carbon dioxide by the East Sea. The research findings were published in Geophysical Research Letters, an international journal by the American Geophysical Union (AGU).

The research team investigated the correlation between the East Sea’s surface-deep circulation and its carbon dioxide absorption capacity, drawing insights from observations in 1992, 1999, 2007, and 2019. During the initial period (1992-1999), the ocean absorbed 20 million tons of carbon dioxide annually. In the subsequent period (1999-2007), this amount decreased to under 10 million tons per year. However, in the final period (2007-2019), the carbon dioxide uptake surged to 30 million tons per year.

The team observed that the internal circulation along the East Coast within the East Sea was influenced by the Arctic cold wave. Cold air from the Arctic infiltrates the East Sea, causing the surface water, laden with carbon dioxide, to become denser. This process induces vertical ventilation as the water descends into the middle and deep ocean layers. Consequently, the intensified descent of cold air from the Arctic strengthens the internal circulation, leading to a heightened uptake of carbon dioxide in the East Sea.

Professor Kitack Lee who led the research remarked, ” The oceans represent an immense reservoir of carbon dioxide and offer a secure and sustainable avenue for mitigating atmospheric carbon dioxide levels.” He further stated, “It is crucial to anticipate the global ocean’s capacity for carbon removal as we navigate future climate changes and identify suitable methods to leverage this potential.”

In a related development, the team’s earlier research uncovered the mechanism through which the ocean absorbs carbon dioxide. Approximately half of the carbon dioxide generated by human activities remains in the atmosphere with the other half entering marine and terrestrial ecosystems. With a carbon content 400,000 times greater than that of the atmosphere, the oceans present vast and promising potential for storing carbon dioxide.

The research was sponsored by the Ocean, Land, and Atmosphere Carbon Cycle System Research Program of the National Research Foundation of Korea and a research contract program of the National Institute of Fisheries Sciences of Korea.