#Diagnostic Materials

[poonamcmi]

IVD Raw Materials: Ensuring Quality Control From Procurement to Production

Raw Material Procurement and Quality Testing The procurement of quality raw materials is the first and crucial step in the production of in vitro diagnostic devices. Various materials like reagents, antigens, antibodies, polymers and minerals are required as raw inputs. To ensure only materials meeting stringent specifications are procured, suppliers undergo a rigorous qualification and audit process.

Critical parameters like purity, potency, IVD Raw Materials  composition and contamination levels are evaluated. Certificates of analysis are reviewed to check if the raw material meets pre-defined acceptance criteria. Periodic re-qualification of suppliers is done to verify they maintain consistent quality over time.

Random sampling and testing is conducted on incoming raw material shipments. Tests include identity verification, quantitative analysis, bioburden screening, endotoxin checks and validation of sterile filtration for heat sensitive components. Any deviations from specifications warrant an investigation and corrective actions before material acceptance. Comprehensive documentation and traceability is maintained for all incoming raw lots.

IVD Raw Materials Storage and Stability Monitoring After acceptance, raw materials are stored as per labeled storage requirements - some may need refrigeration or freezing, while others can be kept at ambient conditions. Designated quarantine and warehouse areas ensure proper segregation.

Environmental conditions of storage areas are continually monitored and recorded to confirm maintenance of set limits. Periodic reviews check for any excursions, equipment breakdowns or process deviations that could impact material stability.

Regular stability monitoring programs assess critical quality attributes of stored raw materials over time. Tests help prove labeled shelf-life or re-test periods and validate that materials maintain suitability for production throughout their intended lifespan. Out-of-specification results prompt corrective measures including rejection or re-processing.

Raw Material Change Control Minor modifications to approved supplier sites, transportation routes or raw material specifications require review and approval to address any potential quality impacts.

Significant changes warrant additional verification activities like method validation, real time and accelerated stability studies on materials manufactured using the changed process. Comparability assessments prove no adverse changes to performance, safety or effectiveness.

Only after successful change validation are revised materials released for commercial production. Rigorous change control safeguards maintain consistent quality of inputs vital for finished product quality and reliability.

Raw Material Quality in the Manufacturing Process Raw material quality directly influences finished product quality. Manufacturing processes are validated to demonstrate robustness even for slight input variability. In-process checks monitor critical parameters.

Materials are properly identified at all stages and batch records capture complete traceability. Environmental controls of manufacturing areas are maintained within pre-set action limits. Cross contamination prevention strategies are in place.

Process simulators and real time release testing help detect early if any raw material deviation may lead to failure to meet pre-defined acceptance criteria for the produced medical devices. Out of specification results trigger investigations.

IVD Raw Materials Related Nonconformities Despite preventive controls, raw material or supplier nonconformities sometimes arise necessitating containment actions. Impacted lots are immediately quarantined and prevented from further use.

Root cause analysis determines corrective measures and extent of trace forward and backward impact on finished devices. Possible device recalls are evaluated if patient safety could be compromised. Lessons learned help strengthen procurement and control strategies.

An effective raw material management system supported by science-based quality oversight enables consistent production of safe and effective IVD products. Continuous improvement further enhances the reliability of this critical first link in the diagnostic device value chain. Get More Insights On, IVD Raw Materials For More Insights Discover the Report In language that Resonates with you

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About Author: Priya Pandey is a dynamic and passionate editor with over three years of expertise in content editing and proofreading. Holding a bachelor's degree in biotechnology, Priya has a knack for making the content engaging. Her diverse portfolio includes editing documents across different industries, including food and beverages, information and technology, healthcare, chemical and materials, etc. Priya's meticulous attention to detail and commitment to excellence make her an invaluable asset in the world of content creation and refinement.(LinkedIn- https://www.linkedin.com/in/priya-pandey-8417a8173/)

[uriekukistan]

light yagami does not have npd or aspd but yall are not ready to discuss this yet

[sublux]

the mmpi-3 is so infuriating. why do i have to take this 335 question assessment when every question is like "i have had very peculiar and strange experiences" ???? i was medically gaslit for 28 years and was literally hours from death at one point because my pain tolerance is so high. i was taken to a nudist colony by my mother at the age of 6. do those count? or are you asking me if i have delusions

[chemmerson]

WHY DO THESE THINGS ALWAYS HAPPEN TO ME!!!!!

[confinesofmy]

i love my therapist!! i love going to see her and always feel productive and healthy after seeing her!!

[nuadox]

Chemists use dinitrogen from air to form critical bonds for energy-efficient industrial synthesis

- By Nuadox Crew -

Chemists at RIKEN have demonstrated that dinitrogen (N₂), a highly abundant molecule in the atmosphere, can be directly used to form a crucial chemical bond, potentially making industrial synthesis of compounds like polymers and drugs more energy-efficient.

Though N₂ is readily available, its strong triple bond makes it difficult to use in chemical reactions. Traditionally, processes like the Haber–Bosch method are required to split dinitrogen into ammonia, followed by additional steps that consume energy and time.

To address this, Takanori Shima and his team discovered that titanium polyhydrides—compounds with titanium and hydrogen atoms—can cooperatively facilitate the formation of alkyl amines from N₂ and alkenes. This method bypasses the need for pre-activated intermediates, activating both substrates and selectively forming nitrogen-carbon bonds.

This breakthrough could streamline chemical synthesis processes, and the team is now working to develop it into a catalytic process.

Header image: Titanium polyhydride (center) directly transforms dinitrogen and a basic alkene (left) into an alkyl amine (right). Credit: Takanori Shima.

Read more at RIKEN

Scientific paper: Shima, T., Zhuo, Q., Zhou, X., Wu, P., Owada, R., Luo, G. & Hou, Z. Hydroamination of alkenes with dinitrogen and titanium polyhydrides. Nature 632, 307–312 (2024). doi: 10.1038/s41586-024-07694-5

--

Other recent news

Radiology: A new portable scanner quickly produces 3D images, aiding in early diagnosis.

[jcmarchi]

Plant sensors could act as an early warning system for farmers

New Post has been published on https://thedigitalinsider.com/plant-sensors-could-act-as-an-early-warning-system-for-farmers/

Plant sensors could act as an early warning system for farmers

Using a pair of sensors made from carbon nanotubes, researchers from MIT and the Singapore-MIT Alliance for Research and Technology (SMART) have discovered signals that reveal when plans are experiencing stresses such as heat, light, or attack from insects or bacteria.

The sensors detect two signaling molecules that plants use to coordinate their response to stress: hydrogen peroxide and salicylic acid (a molecule similar to aspirin). The researchers found that plants produce these molecules at different timepoints for each type of stress, creating distinctive patterns that could serve as an early warning system.

Farmers could use these sensors to monitor potential threats to their crops, allowing them to intervene before the crops are lost, the researchers say.

“What we found is that these two sensors together can tell the user exactly what kind of stress the plant is undergoing. Inside the plant, in real time, you get chemical changes that rise and fall, and each one serves as a fingerprint of a different stress,” says Michael Strano, the Carbon P. Dubbs Professor of Chemical Engineering at MIT and one of the senior authors of the study.

Sarojam Rajani, a senior principal investigator at the Temasek Life Sciences Laboratory in Singapore, is also a senior author of the paper, which appears in Nature Communications. The paper’s lead authors are Mervin Chun-Yi Ang, associate scientific director at SMART and Jolly Madathiparambil Saju, a research officer at Temasek Life Sciences Laboratory.

Sensing stress

Plants respond to different kinds of stress in different ways. In 2020, Strano’s lab developed a sensor that can detect hydrogen peroxide, which plant cells use as a distress signal when they are under attack from insects or encounter other stresses such as bacterial infection or too much light.

These sensors consist of tiny carbon nanotubes wrapped in polymers. By changing the three-dimensional structure of the polymers, the sensors can be tailored to detect different molecules, giving off a fluorescent signal when the target is present. For the new study, the researchers used this approach to develop a sensor that can detect salicylic acid, a molecule that is involved in regulating many aspects of plant growth, development, and response to stress.

To embed the nanosensors into plants, the researchers dissolve them in a solution, which is then applied to the underside of a plant leaf. The sensors can enter leaves through pores called stomata and take up residence in the mesophyll — the layer where most photosynthesis takes place. When a sensor is activated, the signal can be easily detecting using an infrared camera.

The pair of sensors in the leaf consists of one for hydrogen peroxide on the left, and salicylic on the right.  When the plant is wounded, as in this case, the left shows a moving waveform in response, but there is very little production of salicylic acid.  This is the stress signature of wounding.  In contrast, when the plant is stressed by too much heat or light, or a bacterial infection, different waveforms of salicylic acid accompany of the hydrogen peroxide wave on the left.

Image: Courtesy of the researchers

In this study, the researchers applied the sensors for hydrogen peroxide and salicylic acid to pak choi, a leafy green vegetable also known as bok choy or Chinese cabbage. Then, they exposed the plants to four different types of stress — heat, intense light, insect bites, and bacterial infection — and found that the plants generated distinctive responses to each type of stress.

Each type of stress led the plants to produce hydrogen peroxide within minutes, reaching maximum levels within an hour and then returning to normal. Heat, light, and bacterial infection all provoked salicylic acid production within two hours of the stimulus, but at distinct time points. Insect bites did not stimulate salicylic acid production at all.

The findings represent a “language” that plants use to coordinate their response to stress, Strano says. The hydrogen peroxide and salicylic acid waves trigger additional responses that help a plant survive whatever type of stress it’s facing.

For a stress such as an insect bite, this response includes the production of chemical compounds that insects don’t like, driving them away from the plant. Salicylic acid and hydrogen peroxide can also activate signaling pathways that turn on the production of proteins that help plants respond to heat and other stresses.

“Plants don’t have a brain, they don’t have a central nervous system, but they evolved to send different mixtures of chemicals, and that’s how they communicate to the rest of the plant that it’s getting too hot, or an insect predator is attacking,” Strano says.

Early warning

This technique is the first that can obtain real-time information from a plant, and the only one that can be applied to nearly any plant. Most existing sensors consist of fluorescent proteins that must be genetically engineered into a specific type of plant, such as tobacco or the common experimental plant Arabidopsis thaliana, and can’t be universally applied.

The researchers are now adapting these sensors to create sentinel plants that could be monitored to give farmers a much earlier warning when their crops are under stress. When plants don’t have enough water, for example, they eventually begin to turn brown, but by the time that happens, it’s usually too late to intervene.

“With climate change and the increasing population, there is a great need to understand better how plants respond and acclimate to stress, and also to engineer plants that are more tolerant to stress. The work reveals the interplay between H2O2, one of the most important reactive oxygen species in plants, and the hormone salicylic acid, which is widely involved in plants’ stress responses, therefore contributing to the mechanistic understanding of plants stress signaling,” says Eleni Stavrinidou, a senior associate professor of bioengineering at Linköping University in Sweden, who was not involved in the research.

This technology could also be used to develop systems that not only sense when plants are in distress but would also trigger a response such as altering the temperature or the amount of light in a greenhouse.

“We’re incorporating this technology into diagnostics that can give farmers real-time information much faster than any other sensor can, and fast enough for them to intervene,” Strano says.

The researchers are also developing sensors that could be used to detect other plant signaling molecules, in hopes of learning more about their responses to stress and other stimuli.

The research was funded by the National Research Foundation of Singapore and the USDA National Institute of Food and Agriculture.

[mechnicianco]

Empower your heavy equipment diagnostics with Mechnician's Jaltest Heavy Equipment Diagnostic Laptop. Engineered for precision, this portable powerhouse ensures comprehensive analysis and efficient troubleshooting. Stay ahead in the heavy equipment industry with Mechnician's innovative solution, delivering reliability and accuracy in every Diagnostic session.

[macncheesenibblers]

I keep telling my mom she probs has mild ADHD and she says “well I wasn’t diagnosed when I was little so no I don’t” ma’am you grew up in the 60s. Ofc you wouldn’t be diagnosed back then unless you were an extremely obvious case. And then she says “well I only have trouble paying attention to something if it doesn’t interest me. If it interests me I can pay attention really well” like you literally just described ADHD!!!

[painted-bees]

Someone had asked if his behaviour is also technically in line with borderline personality disorder, and while I can definitely understand and see why that would be a consideration, there's a few things that would have run counter to a BPD diagnosis, I think.

-His paranoia isn't something that creeps up once on a semi regular basis to ruin his day. Rather, it's an ever-present thing that informs a lot of his core behaviours and how he structures his life. Depending on how tired, distracted, or vulnerable he is, stmptoms may be easier or more difficult to manage, which can have the outward appearance that his paranoia "comes and goes", but no--it's always there.

-He has a very strong sense of self and identity, he knows who he is he and who he wants to be, and is consistent in his expression/presentation of himself [with the exception being certain CPTSD episodes wherein he might seem to behave a lot more furtive and childishly]. He is just very, very critical of himself and very conscious about how his behaviour affects those around him. He has deliberately constructed a very likable, charming, emptionally "bulletproof" persona to help him navigate and manage his day-to day interactions--but he knows that this is a character he performs for the benefit of the people he interacts with. There's no confusion of it with his actual self-identity.

-He doesn't experience "splitting" nor does he tend to fall wholly into black and white thinking. Even if he were actively in the process of dealing with someone who was treating him poorly and very angry with him [like, say--a bad breakup], while he may absolutely think "they've always had it out for me, this whole situation was inevitable from the start and I failed to stop it on time, I never should have given them the chance to betray me like this, I should have listened to my got on this one", he can still also identify and consider their good qualities. It's just that "trustworthiness" is not among them. Trustworthiness is really the only "off or on" switch--but unfortunately, it's a big one that is almost synonymous with "safe or unsafe", and once someone is found untrustworthy, it is very nearly impossible to ever fully [or truly] claw their way back into being trusted again. But that doesn't make them a villain to him. it just means they are kept at a safe arms length--because they can't be trusted not to hurt him. If they were someone who had gotten to see his more authentic self rather than his "public" character, he likely may never want to see nor hear of them again (they will, no doubt, tell everyone they know what he's really like, and paint him in the most negative possible light[PPD] and he doesn't want to even think about it). But otherwise, if they've only known him as an aquaintence, then they get to remain an aquaintence. Forever...so long as they don't hurt anyone else in his vicinity.

Since I've been rotating Raf's mental illness in my mind this month as a way of smoothing my own brain, I've been thinking a lot about the ways his PPD and CPTSD symptoms interact, and how it affects his behaviors.

Firstly, Raf's paranoia isn't commonly accompanied by narcissistic traits. That is to say--he's not especially prone to believing that people have him on their mind all the time. If he walks past two people laughing, it's not his gut instinct to think that they are laughing at him. However, it is certainly his gut instinct to assume that they are laughing at someone.

But, unless they deliberately pause to regard him in an off putting way, his brain isn't gonna jump to the conclusion that he's the topic of their little chortle.

In fact, Raf rarely feels like he is being deliberately belittled by honest remarks when they are simply worded poorly. In some ways, he greatly prefers being called a jackass, to his face, in flat tones--than to receiving sweet, placating platitudes in a kindly tone. No matter how genuine the kindness may be behind the latter, Raf generally tends to interpret it...poorly. It gives him a really bad gut feeling, like they're buttering him up, mincing their words in a shallow attempt to gain his good opinion...all so that he won't suspect them later. Suspect them of what? Who knows. Something bad, something exploitative, something abusive. To him.

Raf doesn't suspect that everyone is out to use or exploit him. He fully believes that most people are capable of not thinking about him at all--even if he is physically present around them, such as in a busy train station. However, he does suspect that everyone who goes out of their way to interact with him, and especially everyone who wants to get to know him only do so in order to use or exploit him. And his basal understanding of human behavior is, generally, that kindness and good manner are most frequently used as tools of manipulation for personal gain rather than as an expression of genuine love and care. And he recognizes that this is only possible as a successful tool of manipulation because, just like him, everyone else wants to be genuinely loved and cared for.

Even his uncle, whom Raf does genuinely loves and trust, is suspected of being as kind and accommodating as he is to Raf only because doing so soothes his uncle's guilt and gives him a moral leg up over the rest of Raf's family. And part of Raf's initial willingness to trust his uncle is that his uncle never really...denies that this is, at the very least, a part of it. And--if that's all Uncle Bill really wanted outta Raf, then that was a perfectly livable arrangement.

Raf's CPTSD, on the other hand, generates the shame that serves as the crux for a lot of his self-critical introspection. Even before his diagnosis, he was harboring a sense that something was really, deeply wrong with him--like he wasn't a real person. And so, it felt radically audacious to assert that he deserved to behave as a real person; which included the right to feel and act upon anger and sadness--and to have those emotions received and treated with any level of respect by those around him. Until his final year at Juilliard, he was kind of in a placid(listless) state of learned helplessness. He'd do what ever he had to do to meet the expectations of his peers and instructors (namely, amphetamines. So much amphetamines.) It was just baaarely enough to get him his degree, and it ran him ragged and beyond resentful. He fully left Juilliard with the mindset of "I'm entering my villain era, I'm fully committed to being a Bad Guy, I am ok with everyone hating me now". And the "bad guy" behavior was just...saying no to stuff he didn't want to do, self-isolating, and outwardly expressing/lashing out when something viscerally upset him.

Which...thanks to the personality disorder, meant he became prone to yelling at people and accusing them of hurting or betraying him when they, in fact, did not. Especially...almost specifically the people closest to him, who cared the most about him and whom he cared the most for. And that's quickly what lead to his diagnosis, which kinda put an end to his 'villain arch'. So now he's back to reckoning with that sense of "something is really, deeply wrong with me", but at least now he has a growing understanding of what that is. And also the notion of "I have the 'bad person' disease--I am a Bad Person if I act on my core suspicions and beliefs, I cannot fucking trust myself, I can't trust my own perception of people or events." And now he's gotta balance that with whole "I deserve to feel safe, comfortable, and respected" alongside the critical notion of "but so does everyone else".

He hates it when people try to get to know him, he is fundamentally mistrustful of people. But at the same time, he has a lot of difficulty balancing his boundaries against the infringement of other people's boundaries--and the root understanding of "Something is wrong with me, I'm the problem, the fact that I think other people are the problem--is part of the problem that is me." is what motivates him to delay acting upon his negative impulses as much as is is able to, and to exercise kindness even when it feels like he's walking directly into a fire.

So, his overall kinda...thing is "I don't trust any of these guys, they clearly want something from me, and if I let them get close enough, they won't care if they have to hurt me to get it[PPD] but I'm a fundamentally busted person with a fucked up perspective and thus it is actually safer if I prioritize their comfort over my own[CPTSD] within certain parameters[therapy]"

and, idk...the big flashing red "ISOLATE, ISOLATE, ISOLATE" sign shows up in there on a frequent enough occasion that he just...has no real friends, despite a billion "good" acquaintances.

Despite all his mistrust and suspicions, the feelings of being fundamentally unlovable for willfully/protectively limiting the range of his 'usefulness', his terminally pessimistic outlook on the nature of human beings--he craves so tremendously to be loved and cared for and held and reassured in such a way and to such an extent that could never be fully sated, I am sure. But he couldn't stand to receive it from someone he can't believe in.

Margie accidentally hack speedran his CPTSD coping mechanisms so hard that she clipped through his paranoia until the collision error launched her into Trusted Person status. And he's just mostly confused and a bit anxious over how it all happened so fast.

[that's a joke...kinda]

[gg-is-a-loser]

how could no one tell i was autistic growing up i assigned pokémon teams to like every character i ever saw

[interviewhelps]

Top 25 Job Interview Questions for Biomedical engineer

Here are the Top 25 Job Interview Questions for Biomedical engineer Can you tell us about your educational background and how it relates to biomedical engineering? Can you describe a project you have worked on that you are particularly proud of and why? How do you keep up with advancements in technology and the biomedical engineering industry? Can you explain your understanding of the different…

[centralbiohubgermany]

Central BioHub facilitates the acquisition of human biospecimens by connecting global biomedical researchers and scientists to biospecimen suppliers across the globe. Our biospecimen inventory is extensive, with millions of human biological materials acquired from different countries worldwide. Our samples are adequately defined, clinically annotated, and adequately preserved to yield an accurate research endpoint. We are happy to offer the largest supply of standardised human biospecimens on our website, thanks to the growing market trust in our brand.

https://centralbiohubgroup.com/

[primeministerofantarctica]

i heard twilight was originally supposed to be autistic, but i haven't found any sources so i'm taking it with a grain of salt. either way, i feel like there's enough to qualify it as "basically (unintentionally) canon"

also "testing testing 123" is definitely a giant flashing neon metaphor for adhd.

Nopony in that friend group is neurotypical. What're your neurodivergent headcanons for the Mane Six?

[nuadox]

Scientists conceive the world's highest-performing superconducting wire segment

- By Nuadox Crew -

High-temperature superconducting (HTS) wires are seen as a potential game-changer for the future of energy, offering the possibility of transmitting electricity without resistance at temperatures higher than those required by traditional superconductors.

This breakthrough could lead to revolutionary advancements in the electric grid and even make commercial nuclear fusion a reality. However, for these large-scale applications to become feasible, HTS wires must be produced at a price-performance level comparable to that of conventional copper wires.

Recent research led by the University at Buffalo (UB), published on August 7 in Nature Communications, marks a significant step toward this goal. The team has successfully fabricated the world's highest-performing HTS wire segment, achieving a more favorable price-performance metric. The wires, based on rare-earth barium copper oxide (REBCO), set records for the highest critical current density and pinning force—measures of the wire's ability to carry electrical current and stabilize magnetic vortices—across a wide range of magnetic fields and temperatures (5 to 77 kelvin).

Despite the extremely cold temperatures required for HTS wires to operate, ranging from minus 451 to minus 321 degrees Fahrenheit, they are still warmer than the absolute zero required by traditional superconductors. According to Amit Goyal, the study’s corresponding author and a SUNY Distinguished Professor, these results could guide the industry in optimizing the manufacturing process to further improve the cost-effectiveness of HTS wires, enabling their use in various large-scale applications.

HTS wires hold promise for numerous applications beyond just energy transmission. These include doubling the power output of offshore wind generators, enabling grid-scale superconducting magnetic energy-storage systems, and creating highly efficient superconducting transformers and motors. One particularly exciting application is in commercial nuclear fusion, which could generate limitless clean energy. In recent years, about 20 companies worldwide have been founded to develop commercial nuclear fusion, with billions of dollars invested in HTS wire technology.

In addition to energy applications, HTS wires could play a crucial role in next-generation medical imaging technologies, such as MRI and nuclear magnetic resonance (NMR) for drug discovery. They also have potential in defense, particularly in the development of all-electric ships and airplanes. The manufacturing process of these wires incorporates several innovative technologies developed by Goyal and his team, such as rolling assisted biaxially textured substrates (RABiTS) and ion-beam assisted deposition (IBAD) with MgO technology. The wires also benefit from nanocolumnar defects that enhance their performance.

In their latest work, Goyal’s group reported that their HTS wires carried 190 million amps per square centimeter at 4.2 kelvin without any external magnetic field and 90 million amps per square centimeter under a 7 tesla magnetic field. At 20 kelvin, the wires could still carry over 150 million amps per square centimeter in a self-field and over 60 million amps per square centimeter at 7 tesla. These achievements translate into significant advances in the critical current and pinning force of the wires, making them more viable for commercial use.

The fabrication of these high-performance wires involved the use of advanced technologies, such as pulsed laser deposition, to create ultra-thin HTS films with superior current-carrying capabilities. The research also included atomic-resolution microscopy to analyze nanocolumnar and atomic-scale defects, which contribute to the wires' high performance. The study was supported by the Office of Naval Research, with Goyal serving as the principal investigator.

Header image credit: Image Creator from Microsoft Designer/DALL.E (AI-generated)

Read more at University at Buffalo

Scientific paper: A. Goyal, R. Kumar, H. Yuan, N. Hamada, A. Galluzzi, M. Polichetti. Significantly enhanced critical current density and pinning force in nanostructured, (RE)BCO-based, coated conductor. Nature Communications, 2024; 15 (1) DOI: 10.1038/s41467-024-50838-4

Other recent news

Early Cancer Detection: A new blood test in China has achieved 90% accuracy in detecting early-stage gastric cancer.

[jcmarchi]

Inhalable Sensors Could Enable Early Lung Cancer Detection - Technology Org

New Post has been published on https://thedigitalinsider.com/inhalable-sensors-could-enable-early-lung-cancer-detection-technology-org/

Inhalable Sensors Could Enable Early Lung Cancer Detection - Technology Org

Using a new technology developed at MIT, diagnosing lung cancer could become as easy as inhaling nanoparticle sensors and then taking a urine test that reveals whether a tumor is present.

MIT engineers have designed diagnostic particles that can be aerosolized and inhaled. At bottom is a scanning electron micrograph of the particles, which are coated with nanosensors that interact with cancer-associated proteins in the lungs. Illustration by the researchers / MIT

The new diagnostic is based on nanosensors that an inhaler or a nebulizer can deliver. 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 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.

Written by Anne Trafton

Source: Massachusetts Institute of Technology

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