Discovery how droplet microfluidics is revolutionising single-cell analysis and selection in biopharma.
13 ANCIENT DNA REWRITES THE STORIES OF THOSE PRESERVED AT POMPEII
Ancient DNA challenges long-held assumptions about the inhabitants of Pompeii, who died after the eruption of Mount Vesuvius in 79 AD.
15 HOW AI-ENABLED EMBEDDED MODULES ARE ADVANCING MEDICAL TECHNOLOGY
AI has been a longstanding focus in medical technology, and is even being touted as the new operating system for medical devices.
19 THREE-IN-ONE PILL COULD TRANSFORM HYPERTENSION TREATMENT
Phase III clinical trial results indicate that an innovative combination of drugs could revolutionise the management of high blood pressure.
20 AI-DESIGNED DNA SWITCHES FLIP GENES ON AND OFF
The work creates the opportunity to turn the expression of a gene up or down in just one tissue without affecting the rest of the body.
24 MEDITATION TO REDUCE PAIN IS MORE THAN A PLACEBO
Mindfulness meditation had been speculated to work by activating
processes supporting the placebo response, but this is not the case.
26 LOW GRAVITY DISRUPTS NORMAL RHYTHM IN HEART MUSCLE CELLS
Bioengineered heart tissues that were sent to the International Space Station did not fare well during their time there.
29 SENSITIVE GAS MEASUREMENT WITH A NEW SPECTROSCOPY TECHNIQUE
The technique offers a faster, more flexible and more sensitive way to analyse substances in the air and other materials.
32 A SCIENCE-BASED SOLUTION FOR TACKLING LAKE HEALTH
The water quality in lakes is declining at an alarming rate, leading to severe repercussions.
Gene genies
Acouple of years ago, we reported on species preservation company Colossal Biosciences’ lofty ambition to bring the Tasmanian tiger back from extinction, in partnership with The University of Melbourne’s Thylacine Integrated Genetic Restoration Research (TIGRR) Lab. It may have seemed like a pipe dream at the time, but the company has recently announced a number of breakthroughs suggesting its mission is far from over.
The Colossal team claim to have produced a newly reconstructed thylacine genome, assembled to the level of chromosomes, that is estimated to be >99.9% accurate; it even includes hard-toassemble repetitive features such as centromeres and telomeres, which are challenging to reconstruct even for living species. It also has only 45 gaps, which will apparently be closed by additional sequencing efforts over the coming months.
The high quality of the new thylacine genome, which is around three billion bases in length, is due to the unusual preservation of long DNA sequences (most ancient specimens retain only short DNA sequences with little to no RNA, due to degradation that happens after the organism dies). The team were also able to isolate long RNA molecules from a 110-year-old thylacine head that had been skinned and preserved in ethanol, which probably led to the exceptional quality of the RNA.
In related news, Colossal has provided an update on its efforts to engineer resistance to cane toad toxin into marsupial cells, with the company claiming to have created over 6000-fold increased resistance in the northern quoll with just one edit to the genome. Colossal researchers have also derived the first induced pluripotent stem cell (iPSC) lines for quolls, which they created using their approach for making iPSCs for the fat-tailed dunnart. These iPSCs are essential for making a living quoll that carries the cane toad toxin resistance in its genome; iPSCs are also important for conservation efforts including biobanking, cloning, breeding and genetic engineering work.
These two projects clearly demonstrate some remarkable breakthroughs in genomics, and so we have devoted a couple of articles in this issue to this fascinating area. Our cover story, which you will find on page 13, explores how DNA has been extracted from ancient skeletons in Pompeii, providing new information and challenging long-held assumptions about the individuals in question. A separate article, on page 20, details the creation of AI-designed DNA ‘switches’ that can activate genes in brain, liver or blood cells without turning on these genes in other cell types. Other articles of interest this issue cover the power of mindfulness meditation for pain management, on page 24 (turns out it’s not ‘hippie rubbish’ after all!); a new laser-based technique that could improve our ability to analyse a variety of materials and gases (page 29); and a look at how
the low-gravity conditions of space can weaken heart tissues (page 26).
On a final note, you’re probably reading this issue in late December or early January, which means it should be prime beach weather. I’m sure you don’t need me to remind you to steer clear of any mysterious black balls that may wash up on the shore, but in case you need a refresher, the so-called ‘tar balls’ that appeared on Sydney’s beaches back in October ended up containing traces of cooking oil and soap scum, PFAS chemicals, human faecal waste, pesticides, medications, recreational drugs and more — which pointed to sewage and other sources of urban effluent as the most likely origin of the blobs, although this is yet to be confirmed. All this is to say — have a good summer, and stay curious, but not too curious!
Lauren Davis
Regards, Lauren Davis
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Droplet microfluidics for single-cell analysis
The next generation of capability
Droplet microfluidics is revolutionising single-cell analysis and selection in biopharma, writes Richard Hammond*.
Droplet microfluidics is an established technology for single-cell analysis, characterisation and selection. Cells are encapsulated in droplets of a suitable aqueous media contained in an oil carrier fluid and the droplets are stabilised with a surfactant. The droplets are produced using microfluidic methods, where liquids are pumped through carefully designed geometric channels at the micrometre scale (Figure 1). By varying the relative flow rates of the cell suspension and oil carrier fluid, the distribution of the number of cells per droplet can be controlled, particularly to obtain predominantly single cells per droplet based on the Poisson statistical distribution. These droplets can then be subjected to different operations all within the closed microfluidic system.
The adoption of this technique within biopharma is driven by the real-world benefits it brings:
• Localisation: Individual droplets form self-contained reaction vessels which allow secreted molecules to be analysed as well as surface markers. The very small droplet volumes allow rapid increase in concentration of the target to support robust assay performance.
• Benign environment: Cells are encapsulated in their preferred medium and the oil phase supports gas exchange, and the droplet shields
the cell from the shear forces imparted by the microfluidics. Thus, droplets are particularly suited to applications where the cell must maintain viability post assessment.
• Speed and scale: Droplets can be created and processed at high speed, typically into the kHz range. This allows every member of a large cell population to be assessed in a few hours.
• Automation: The flow of droplets through microfluidic channels provides a robust and adaptable platform to automate complex workflows — particularly for selecting cells — and minimise user workload.
• Cost: The small size of the droplets requires minimal amounts of reagent so even largescale experiments can be performed cost effectively.
Figure 1: Droplet generation process to encapsulate a single cell per droplet.
A key use case of the technology is cell selection. Here, the need is to start with a large viable heterogeneous cell population and find the
much smaller subset of cells with certain desired phenotypes while retaining viability (Figure 2).
The challenge is to find the most efficient way to move from the general to the specific. Typically, today this process is done in multiple steps using different equipment with the concomitant time and effort needed to run long multi-step workflows. However, droplets provide an approach that can move further and further towards the ideal: doing the whole process in one step from millions of cells to single digits.
The dominant technique used today for the assessment of cells in droplets is fluorescence. This builds on the years of experience in flow cytometry where fluorophores provide a robust signal that can be converted into an electrical signal for logging and processing; and in a format that can be integrated into a bioassay.
Delivering this ideal requires improvements in two areas:
Figure 2: The cell selection challenge — going from the general to the specific as efficiently as possible. Dotted lines represent selection criteria; the better the criteria, the closer the boundary to the bottom right-hand corner.
• Asking more precise questions: For example, instead of screening cells for presence or absence of a generic, conserved, phenotype (such as the Fc region of an antibody), screen for the presence of absence of the precise target of interest. Another example would be quantification, moving from a basic presence/ absence test to a quantified measure to identify and select only high-producing cells.
• Asking multiple questions at the same time: For example, screen for several markers simultaneously and only accept cells displaying all the markers.
The next generation of droplet-based platforms is tackling these improvements. It requires improvements in all aspects of the technology, but particularly assay and detection technologies.
Antigen-specific techniques require new assay approaches, where the user can integrate the desired antigen into a standardised assay quickly and easily for screening. New labelling kits are needed, optimised for the unique properties of the droplet format.
Beyond more specific assays, providing robust quantification in droplets is also technically difficult. The entire measurement system is complex — cell, assay, droplet, consumable, instrument — and the first challenge is providing the underlying precision to provide a repeatable measurement. Delivering this requires great attention to detail in design, component selection and manufacture. The second challenge is then calibration, referencing back all measurements made to defined standards. This will require innovation in the use of fluor standards in the context of droplet-based systems and how this is integrated into the assay format.
Droplets are uniquely suited to addressing the multiplex challenge as they can support both secreted and surface marker identification (Figure 3). The secreted molecules can be used either to cleave fluorophore/quencher structures or to bind donor/acceptor pairs in a Förster resonant energy transfer (FRET) type approach thus providing a varying fluorescent signal as the marker is expressed. Alternatively, secreted molecules can be used to generate a fluorescence response, for example using a reporter cell. Conversely, surface markers can be labelled in the more traditional way to generate a localised fluorescent response within the droplet.
As an example of the power of multiplexing, Figure 4 shows data assessing a diffuse marker (a FRET assay) and a localised marker (a cell staining dye) simultaneously. Using gate 1, the population of cells showing FRET response can be selected; and at the same time the two cell types (stained red and blue) can be identified.
Droplet-based systems will continue to play a key part in cell selection workflows as
these increasingly sophisticated approaches are developed and brought to market. Novel assays, accurate quantification and deep multiplexing will combine to provide the next generation of capability to identify and select the most important viable cells from increasingly large starting populations quickly and efficiently. Going from millions of cells to single-digit numbers is getting closer.
*Richard Hammond is Chief Technical Officer at Sphere Fluidics, a company developing single-cell analysis systems underpinned by its patented picodroplet technology. Richard has over 20 years’ experience in managing the development of novel commercial products for healthcare and life sciences. He has held numerous senior positions, including leading product and technology development at Alere Inc, Cambridge Consultants Ltd and DNA Electronics Ltd. With extensive technical expertise, he has worked in cutting-edge technical areas, such as isothermal molecular diagnostics, automated cell transfection, CAR T cell therapy manufacture and digital data storage in DNA. Richard holds MA and MEng degrees in engineering from King’s College, University of Cambridge.
Figure 3: Droplets can support both secreted and surface marker detection, a key benefit for deep multiplexing.
Figure 4: Fluorescent multiplexing in droplets assessing both FRET response (gate 1) and cell stain (gate 2) simultaneously.
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The Beamex MC6-T is an extremely versatile portable automated temperature calibration system. It combines a state-of-the-art temperature dry-block with Beamex MC6 multifunction process calibrator and communicator technology.
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It offers versatility, that no other temperature calibrator can match.
FDA approves new treatment for graft-versushost disease
The US FDA has fast-tracked approval of a drug based on findings by QIMR Berghofer researcher Dr Kelli MacDonald, a decade after her breakthrough discovery of an antibody that could prevent chronic graft-versus-host disease (GVHD).
Chronic GVHD — a major cause of complications and death in blood cancer patients who receive vital stem cell transplants — occurs when the transplanted cells attack the recipient’s organs and tissues. This causes scarring, which can lead to debilitating and often long-lasting health problems — particularly in the skin and lungs.
Back in 2014, MacDonald’s lab at QIMR Berghofer identified the cellular process causing chronic GVHD as well as the antibody that could block this process and prevent the disease’s development. The resulting drug, axatilamab, has now been shown in clinical trials to suppress harmful immune cells and prevent the development of chronic GVHD (as described in The New England Journal of Medicine).
“This is an important and exciting development for people with GVHD and has been over a decade in the making from our initial research,” MacDonald said, with the FDA-approved drug expected to meet the urgent needs of a large proportion of patients with chronic GVHD who fail to respond to initial steroid-based therapy.
“Until recently, there has been no satisfactory treatment for people affected by this debilitating condition which causes inflammation and fibrosis in tissues throughout the body. However, this new treatment has significantly reduced symptoms in up to 75% of patients.”
Healthcare providers will soon be able to access full prescribing information on the FDA’s website as the drug becomes available in the USA. It is not yet known when the treatment will become available in Australia.
“This approval is a big step forward for people dealing with the challenges of chronic GVHD and offers a new option for those who have struggled to find effective treatment,” MacDonald concluded.
CRISPR molecular scissors can introduce genetic defects
CRISPR molecular scissors have the potential to revolutionise the treatment of genetic diseases, as they can be used to correct specific defective sections of the genome. Unfortunately, the repair can lead to new genetic defects when it comes to treating chronic granulomatous disease, as reported in the journal Communications Biology
Chronic granulomatous disease is a rare hereditary disease that affects about one in 120,000 people. The disease impairs the immune system, making patients susceptible to serious and even life-threatening infections. It is caused by the absence of two letters, called bases, in the DNA sequence of the NCF1 gene. This error results in the inability to produce an enzyme complex that plays an important role in the immune defence against bacteria and moulds.
Researchers at the University of Zurich succeeded in using the CRISPR system to insert the missing letters in the right place, as demonstrated in cell cultures of immune cells that had the same genetic defect as people with chronic granulomatous disease. However, some of the repaired cells now showed new defects — entire sections of the chromosome where the repair had taken place were missing.
The reason for this is the special genetic constellation of the NCF1 gene: it is present three times on the same chromosome, once as an active gene and twice in the form of pseudogenes. These have the same sequence as the defective NCF1 and are not normally used to form the enzyme complex.
CRISPR molecular scissors cannot distinguish between the different versions of the gene and therefore occasionally cut the DNA strand at multiple locations on the chromosome — at the active NCF1 gene as well as at the pseudogenes. When the sections are subsequently re-joined, entire gene segments may be misaligned or missing. The medical consequences are unpredictable and, in the worst case, contribute to the development of leukaemia.
To minimise the risk, the team tested a number of alternative approaches, including modified versions of CRISPR components. They also looked at using protective elements that reduce the likelihood of the genetic scissors cutting the chromosome at multiple sites simultaneously. Unfortunately, none of these measures were able to completely prevent the unwanted side effects.
According to study co-author Professor Martin Jinek, the research provides valuable insights into the development of gene-editing therapies for chronic granulomatous disease and other inherited disorders. Ultimately, he concluded that further technological advances are needed to make the method safer and more effective in the future.
Common heart medicine may be causing depression
All patients who have had a heart attack are typically treated using beta blockers, but it turns out these drugs are unlikely to be needed for those patients who have a normal pumping ability. What’s more, there is also a risk that these patients will become depressed by the treatment.
Beta blockers are drugs that block the effects of adrenaline on the heart and have been used for decades as a basic treatment for all heart attack patients. In recent years, their importance has started to be questioned as new, successful treatments have begun to be developed. This is mainly the case for heart attack patients whose heart has a normal pumping function even after the attack, meaning they do not suffer from heart failure.
Researchers at Uppsala University wanted to look at the side effects of beta blockers; that is, whether they affect anxiety and depression levels. This is because older research and clinical experience suggests that beta blockers are linked to negative side effects such as depression, difficulty sleeping and nightmares.
Earlier this year, the results of a major study published in The New England Journal of Medicine revealed that those who received betablocking drugs were not protected from relapse or death compared to
those who did not receive the drug. The Uppsala researchers based their work on this study, conducting a sub-study which ran from 2018 to 2023. The study involved 806 patients who had had a heart attack but no problems with heart failure — half were given beta blockers and the other half were not. About 100 of the patients receiving beta blockers had been taking them since before the study, and the researchers observed more severe symptoms of depression in them. Their findings were published in the European Heart Journal. Acute Cardiovascular Care
“We found that beta blockers led to slightly higher levels of depression symptoms in patients who had had a heart attack but were not suffering from heart failure,” said doctoral student Philip Leissner, the study’s first author. “At the same time, beta blockers have no life-sustaining function for this group of patients.
“Most doctors used to give beta blockers even to patients without heart failure, but as the evidence in favour of doing so is no longer so strong, this should be reconsidered,” Leissner continued. “We could see that some of these patients appear to be more at risk of depression. If the drug doesn’t make a difference to their heart, then they are taking it unnecessarily and at risk of becoming depressed.”
Single-molecule imaging enables large-scale drug screening
As part of the drug discovery process, researchers must first identify molecules in the body’s cells that help drive disease; then, they must screen candidate drugs that can hit those targets. Now, scientists at Osaka University are using single-molecule tracking to explore the effects of many different candidate drugs on a single target molecule.
Building on the team’s large-scale intracellular single-molecule imaging system, referred to as AiSIS, the technology screens new drugs 100 times faster than standard manual techniques, which can be challenging and time-consuming process. The technique has been described in the journal Nature Communications
The team used their new method to screen drugs that can target the epidermal growth factor receptor (EGFR), a molecule central to the development and progression of various cancers. Because several drugs
that block EGFR are already available to treat lung cancer, this was a good way to determine how well their screening approach worked.
“We used a library of over 1000 approved drugs to validate our screening method,” said Daisuke Watanabe, lead author of the study. “We successfully identified all the drugs that are known to target EGFR and are currently used to treat cancer patients. More importantly, we found that the library included seven drugs that until now were not known to affect EGFR.”
The new imaging technique visualises the behaviour of EGFR following treatment with each drug, allowing the researchers to examine how it reacted. For example, it is now possible to see changes in the assembly and disassembly of target molecules in response to drug treatment, a process known as multimer formation.
“Screening using single-molecule imaging provides a new means to discover drugs by observing the movement of biomolecules in cells and the formation of multimers,” said senior author Masahiro Ueda. “This has not been used for drug discovery until now, and it means we should be able to develop new drugs with different mechanisms of action and even repurpose already approved drugs to new targets.”
With the researchers’ method working as expected on the the wellknown EGFR target, they can now use this approach to screen drugs that could potentially hit an array of other receptor targets that are closely involved in disease development and progression.
Robotic hand helps cultivate baby corals for reef restoration
Researchers at CSIRO say they have developed a world-first soft robotic hand, or gripper, that could revolutionise the delicate, labour-intensive process of cultivating baby corals in laboratories, offering a groundbreaking new approach to coral restoration efforts.
The gripper was designed to be attached to a coral farming robot called Coral Husbandry Automated Raceway Machine (CHARM), invented by the President of Beyond Coral Foundation, Stephen Rodan. The foundation aims to deploy this technology in aquariums and coral farms worldwide, enabling the large-scale production of coral to restore reefs.
The gripper project is part of CSIRO’s Kick-Start program, which offers dollar-matched funding and access to research expertise to Australian startups and small and medium-sized enterprises (SMEs). Dr Josh Pinskier, Soft Robotics Scientist at CSIRO’s Data61, said the project aims to partially automate the time-consuming process of coral propagation.
“Cultivating hundreds or thousands of baby coral colonies in the lab demands significant effort and precise handing,” Pinskier said.
“Each coral must be carefully transferred between tanks to maintain ideal growing conditions, a process currently managed entirely by hand.
“This gripper replicates the dexterity of a human hand, allowing it to handle delicate coral tissue without damaging them, while being strong enough to lift various sizes.
“By automating this process, we can contribute to broader global efforts to scale coral farming and help restore the world’s reefs.”
The grippers were designed using CSIRO’s AI-powered generative design algorithms, which identified the optimal structures to safely and effectively handle delicate coral.
Sarah Baldwin, a Mechatronics Engineer who conducted the research while at CSIRO, said the gripper design was innovative due to traditional robotics’ unsuitability in corrosive salt water.
“To overcome corrosion, we 3D-printed the gripper from hard polymer and soft rubber, with only a few screws and bolts,” Baldwin said.
Rodan said this is the first time in history that a robot apparatus has ever picked up a coral and transferred it safely between tanks using a soft robotic gripper of this kind. The gripper is just one of several attachments CHARM can support, alongside tools such as a soft brush for removing algae, further streamlining coral farming operations.
Rodan said the partnership with CSIRO has provided the specialised engineering capability needed to advance Beyond Coral Foundation’s reef restoration efforts. “The next challenge is placing the corals back in their natural habitat, and a well-designed gripper could facilitate the transition from growth to deployment,” he said.
The soft robotic ‘hand’ transporting a baby coral.
Ancient DNA rewrites the stories
of those preserved at Pompeii
Researchers from the University of Florence, Harvard University and the Max Planck Institute for Evolutionary Anthropology have used ancient DNA to challenge long-held assumptions about the inhabitants of the city of Pompeii, reporting their findings in the journal Current Biology.
In 79 AD, the active volcano known as Mount Vesuvius experienced one of its most significant eruptions, burying the Roman city of Pompeii — as well as the nearby town of Herculaneum — under a thick layer of small stones and ash known as lapilli. Many of Pompeii’s inhabitants lost their lives as their homes collapsed under the weight of the lapilli raining down from many kilometres above, while those who survived the initial phase of the eruption eventually succumbed to dangerous pyroclastic flows — fast-moving streams of hot gas and volcanic matter that instantly enveloped them in a solid layer of ash, effectively preserving their bodies and features.
Although the soft tissue decayed, the outlines of the bodies remained and were recovered by excavators centuries later by filling the cavities with plaster — which led to certain assumptions about the victims’ sex and kinship based on their physical appearance and the positioning of the casts. But the research team, who had heard the stories of Pompeii, realised that ancient DNA and
strontium isotopes used to date samples could help them to better understand the diversity and origins of Pompeii’s residents.
The team managed to generate genome-wide ancient DNA and strontium isotopic data from highly fragmented skeletal remains that were embedded in the plaster casts, focusing on 14 casts that were undergoing restoration. This allowed them to determine the genetic relationships, sex, ancestry and mobility of five individuals.
Interestingly, this DNA evidence shows that individuals’ sexes and family relationships don’t match traditional interpretations that had been formulated largely from modern-day assumptions.
“The scientific data we provide do not always align with common assumptions,” said David Reich of Harvard University. “For instance, one notable example is the discovery that an adult wearing a golden bracelet and holding a child, traditionally interpreted as a mother and child, were an unrelated adult male and child. Similarly, a pair of individuals thought to be sisters, or mother and daughter, were found to include at least one genetic male.”
“The findings challenge enduring notions such as the association of jewellery with femininity or the interpretation of physical proximity as
evidence of familial relationships,” noted Professor David Caramelli, from the University of Florence.
The genetic data also provided information about the ancestry of the Pompeiians, who had different genomic backgrounds. They primarily descended from recent immigrants from the eastern Mediterranean — a finding which highlights the cosmopolitan nature of the Roman Empire, the researchers said.
“Our findings have significant implications for the interpretation of archaeological data and the understanding of ancient societies,” said Alissa Mittnik, from the Max Planck Institute. “They highlight the importance of integrating genetic data with archaeological and historical information to avoid misinterpretations based on modern assumptions. This study also underscores the diverse and cosmopolitan nature of Pompeii’s population, reflecting broader patterns of mobility and cultural exchange in the Roman Empire.”
“It is also likely that the use of these casts for narration purposes could have led to past restorers modifying their postures and placements,” Caramelli added. “The combined use of genetic data and other bioarchaeological methods provides us with the chance to better comprehend the lives and habits of the victims of the Vesuvius eruption.”
Casts from the House of the Cryptoporticus, created in 1914.
Holotomography system
The HT-X1 Plus Holotomography system extends the reach of holotomography to an even broader array of challenging specimens — including dense organoids, tissue sections and fast-moving microorganisms. The state-of-the-art bioimaging platform is designed to empower researchers with the precision, efficiency and reliability needed for applications in 3D biology, immunology, regenerative medicine and cell biology.
Equipped with a high-spec sCMOS camera featuring a 4x larger field of view and reduced acquisition time compared to previous models, the HT-X1 Plus can be used for high-throughput phenotypic screening of cells and organoids without the need for stitching. Its upgraded correlative imaging capabilities — incorporating a sCMOSbased fluorescence module — enable seamless integration of molecular studies with single-cell-resolution 3D images. Users can experience clear, detailed imaging of multi-layered specimens with improved illumination optics and advanced image reconstruction algorithms. Imaging can be customised with three wavelength options to enhance contrast or improve penetration.
The system offers high content screening of live cells and organoids, making it suitable for high-content, image-based drug screening research. High-resolution imaging of 3D biological samples is especially advantageous for research involving 3D cultures, enabling the detailed investigation of dense organoids and intact tissue sections. Enhanced correlative fluorescence imaging is possible with the fluorescence module (FLX), featuring an sCMOS camera designed specifically for precise signal intensity measurements. With the colour brightfield imaging modality and wide preview scan features, researchers can gain deep insights into histological tissue section studies.
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RNA isolation kits
Norgen Biotek introduces the EXTRAClean series of RNA isolation kits, designed to provide better representation of small RNA species from exosomal and cellfree RNA samples. This should lead to better sequencing results from these low-input sample types.
Traditional methods often yield RNA with background contaminants, leading to costly sequencing reads that do not map efficiently to the genome. With EXTRAClean, Norgen’s innovative RNA isolation technique enables minimal background noise, which should result in reduced unmapped reads and up to a 10-fold increase in microRNA mapping during sequencing runs.
Suitable for applications in exosomal RNA and cell-free RNA studies, the kits support various low-input sample types such as plasma, serum, urine and more. This enhancement not only improves sequencing efficiency but can also reduce overall sequencing costs by maximising data quality through high RNA purity, the company says.
With EXTRAClean, Norgen Biotek continues its mission to help researchers and clinicians gain access to tools that improve research experience and outcomes. The company’s dedicated tech support team is ready to assist with any product or application-related questions.
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Gel casting system
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How AI-enabled embedded modules are advancing medical technology
Maximilian Gerstl* and Zeljko Loncaric^
For decades, medical device manufacturers have been at the forefront of innovation, utilising artificial intelligence (AI) since the 1990s to significantly enhance medical imaging and data analysis. The evolution of high-performance hardware AI accelerators and the advent of machine learning (ML) for training AI algorithms in the 2000s have further refined image analysis, leading to more accurate and efficient interpretations and, consequently, improved patient outcomes.
Today, a diverse range of medical devices benefit from AI integration. This includes high-performance stationary medical imaging equipment such as MRI and CT scanners, as well as more compact and mobile ultrasound and X-ray devices. Patient monitoring systems and surgical robots are also harnessing AI. Furthermore, AI is enhancing applications in laboratory settings, powering various blood analysers and genome sequencers. The development, application and significance of AI in medical technology have gained substantial momentum over the past decade. This
progress is driven not only by continuous advances in computer technology but also by optimisations in AI algorithms. It is a collective effort of medical professionals, technology developers and stakeholders in the healthcare industry that is driving this significant change.
Recent advancements in AI
A recent example of the importance of AI advancements for medical imaging is the innovative AI algorithm for MRI. This algorithm has revolutionised the scanning process, enabling scans to be completed in less than a minute, thereby reducing the time patients spend in the scanner. The key is the AI-based computing of upscaling or super-scaling. This process requires fewer images than traditional methods, meaning it is faster. The pre-trained
AI interpolates a small number of individual images into a high-resolution overall image. Moreover, the AI can independently and accurately sharpen blurry areas within images, demonstrating the power of AI in improving medical imaging.
AI is also being integrated into endoscopy devices, for instance, to alert doctors to lesions during examination in real time and directing their attention to specific areas of concern. High-performance inference is crucial to ensure that the trained models execute swiftly to happen instantly. AI-based endoscopy devices provide doctors with a powerful tool to achieve more accurate clinical results and deliver better patient care.
Beyond diagnostic devices, AI plays a crucial role in therapeutic equipment such as ventilators. In these systems, AI algorithms are trained to continuously analyse critical patient data and automatically adjust parameters like respiratory rate, tidal volume and oxygen supply.
AI accelerators integrated
Dealing with massive volumes of data requires computing architectures capable of handling the data load. To achieve the necessary performance, engineers used either a dedicated general-purpose graphics processing unit (GPGPU), often integrated via the classic PCIe slot and relatively large and power-hungry, or a smaller AI accelerator card designed for an M.2 slot.
Today, more and more processor manufacturers are adapting their chip portfolios to meet the demands of AI. By integrating AI functions directly into their processors, many medical applications can now be realised easily, quickly and at a lower total cost of ownership (TCO), eliminating the need for additional accelerator or dedicated graphics cards.
The first generation of Intel Core Ultra processors (Figure 1) exemplifies this trend. These processors combine a CPU, a particularly powerful GPU and — for the first time — a neural processing unit (NPU) on a single chip. AI applications with high computing power demands can leverage the combined power of all three processors. In contrast, the CPU can be used to handle quick, lightweight tasks. The GPU that can also be used as a GPGPU for computational tasks is best for large workloads requiring parallel throughput, and sustained, heavily-used AI workloads requiring high performance per watt can be optimised to run on the NPU.
The Intel NPU executes ML algorithms and AI inferencing with approximately 20x greater energy efficiency than standard x86 instruction set architectures. For image classification tasks, applications can utilise the graphics unit as a GPGPU, achieving performance levels comparable to discrete GPUs. This results in 1.9x faster graphics or GPGPU processing, enabling a more detailed, meaningful and immersive user experience. These AI features can be easily implemented using a standardised computer-onmodule (COM), particularly COM Express, without requiring developers to modify existing designs.
Modular compute provides high flexibility
As AI and its applications evolve, the flexibility of COM and carrier board solutions allows developers to adapt their products to new computing requirements with minimal integration effort and software modifications. They just need to follow two simple steps: unplug the old module and plug in the new one.
One such COM suitable for demanding edge AI workloads is the congaTC700 (Figure 2). This COM Express Type 6 Compact module, powered by Intel Core Ultra processors, integrates all the necessary AI functions for the applications previously discussed.
Figure 1: The Intel Core Ultra processors integrate a CPU and GPU as well as a dedicated AI engine — the NPU — for energy-efficient AI calculations.
Figure 2: The congaTC700 is suitable for real-time compute and AI applications requiring high reliability and fanless operation.
The conga-TC700 provides application-ready AI capabilities in a plugand-play COM Express form factor. Its 10-year availability and the ease of upgrading applications enable powerful real-time computing and offer highperformance AI functions for various medical applications, including surgical robots, medical imaging systems and high-resolution diagnostic workstations.
Developing and optimising AI models
Beyond the new edge AI capabilities of the Intel Core Ultra platform, Intel also offers the Intel Geti software framework. This comprehensive computer vision AI platform enables medical device engineers to rapidly develop AI models with limited coding resources. Developers benefit from a unified ecosystem spanning ML in the cloud to AI-accelerated edge devices.
The congatec COM ecosystem is further enhanced by the Intel opensource software AI toolkit, OpenVINO. This tool allows for the optimisation and transfer of pre-developed, often hardware-specific, AI models to the medical device manufacturer’s platform, regardless of where they were created. OpenVINO can also manage workload distribution, intelligently deciding which tasks should be handled by the CPU, GPU or NPU for maximum efficiency.
Conclusion
AI has been a longstanding focus in medical technology, predating its adoption in other industrial markets. AI is even being touted as the new operating system for medical devices. Recent advancements in semiconductor technology have yielded microprocessors with exceptionally high compute power and graphics performance. Featuring integrated NPU units, they enable faster, more accurate diagnoses while consuming less energy than predecessors. When implemented through COMs, today’s AI-supported medical devices become highly futureproof, making it easy to integrate upcoming technologies by simply swapping the module.
*Maximilian Gerstl is a Product Line Manager and AI expert at congatec.
^Zeljko Loncaric is Market Segment Manager for Medical and Infrastructure at congatec.
Sample management software supports drug discovery sector
Griffith University’s Compounds Australia, understood to be Australia’s only dedicated compound management facility, has selected Titian Software’s Mosaic Sample Management platform to manage its extensive compound collection and support future growth. Mosaic is set to enable optimisation of workflow efficiencies at Compounds Australia, underpinning the facility’s strategic growth to meet the needs of a growing drug discovery sector.
Compounds Australia plays a critical role in advancing drug discovery, managing a diverse collection of over 1.5 million samples and supporting approximately 50 member organisations worldwide. The academic facility provides researchers with access to highvalue compound libraries as well as the specialist expertise and infrastructure required to screen those libraries in high throughput.
Following year-on-year growth since its establishment in 2007, Compounds Australia had outgrown its in-house sample management software. Recognising the need for a more scalable solution, it selected Titian, a market leader in life sciences sample management software with 25 years of expertise, to help futureproof operations.
Laboratory integrations are a leading factor in Compounds Australia’s adoption of Titian’s Mosaic platform. Compounds Australia will integrate its existing Hamilton Verso and Q series stores along with the Azenta SampleStore solutions using Mosaic’s off-theshelf integrations. To further enhance the data flow and automation of sample handling processes, Mosaic will also be integrated into fulfilment platforms including HighRes Biosolutions, Beckman Coulter Access and, in the near future, the Thermo Scientific Momentum system. This should optimise efficiency, minimise risks, reduce manual interventions and free up valuable resources.
Dr Nyssa Drinkwater, Manager at Compounds Australia, expressed her enthusiasm for the new partnership.
“Titian has an excellent understanding of our business and clients’ needs in sample management,” she said. “Sample management is at the core of Titian’s business, and the Mosaic platform — customised to our needs by industry experts — will position us well for future growth and allow us to support an expanding client base. I am excited to start this partnership with Titian.”
Rebecca Lang, Compounds Australia Operations Manager, added, “Meeting the wide diversity of our clients’ needs has always been critical to Compounds Australia’s operations. Mosaic’s modular design will enable us to maintain that flexibility without an extensive development time, allowing us to rapidly implement the platform and scale up our services to drive more research forward.”
Angela Gray, Vice President of North and South America Sales at Titian, concluded, “Compounds Australia is a critical resource for drug discovery in the region. We are proud to be a part of their continued success and growth in the global research community.”
Titian Software www.titian.co.uk
Vaccine refrigerator with UPS battery backup
PSS Distributors has partnered with medical cold-storage manufacturer Vacc-Safe to introduce Vacc-Safe PowerGuard, a vaccine refrigerator with an integrated UPS battery backup. This helps keep vaccines stored under optimal conditions — even during power outages — meeting stringent government regulations.
The integration of a backup battery into a vaccine-safe refrigerator provides peace of mind to healthcare providers, keeping vaccines effective and safe for use even in the event of a power failure. It also reduces the hassle of having to buy and install a separate backup battery. In accordance with government regulations, all vaccines must be stored in a purpose-built vaccine refrigerator that is data-logged and reviewed at least weekly. The vaccine refrigerator includes continuous data logging and weekly data-reporting capabilities, as well as a streamlined high-precision temperature control and all-in-one design that eliminates the need to have a separate refrigerator and bulky UPS battery backup system.
PSS Distributors www.pssdistributors.com.au
Image: Supplied.
Multifunctional flow computer
Process Control’s UNIFLOW-200 MFC (multifunctional flow computer) is a flexible platform that is suitable for demanding flow measurement applications.
The product works with any flowmeter — including pressure differential devices, ultrasonic, turbine, vortex, mass flow and many more — and measures eight fluid flows in closed circuits simultaneously according to current international standards. It further calculates the physical properties of more than 30 fluids (gases, liquids and steam).
The flow computer supports HART transmitter protocols, has serial interfaces for gas chromatographs and ultrasonic flow meters (Modbus and Instromet US meter protocols), and can store hourly readings for up to 400 days. Besides custody transfers, it is applicable as a flow computer for process applications or for calculating CO 2 emissions.
Automated brightfield cell counter with machine learning capabilities
The LUNA-III is the latest addition to Logos Biosystems’ line of LUNA automated cell counters, which includes the popular LUNA-II, LUNA-FL and LUNA-FX7 automated cell counters.
The LUNA-III is equipped with machine learning capabilities to help users expand research capacity and improve lab workflow and efficiency. Integrating the advanced algorithms provides high levels of cell counting accuracy, even in highly aggregated samples, the company says.
Logos Biosystems says its autofocus mechanism with precise control offers enhanced cell recognition and measurement, resulting in high image quality. This allows optimal decision-making for downstream processes and protocols, which should ultimately increase lab productivity and workflow.
The new Reanalysis feature, useful for diverse cell types, enables users to refine protocols, conserve samples and eliminate additional prep work. The LUNA-III also provides seamless data management with internal storage, USB support and network connectivity, allowing easy data storage, retrieval and transfer to a desktop or laptop computer.
The LUNA-III is compatible with the LUNA Reusable Cell Counting Slide (just like the other LUNA family automated cell counters), offering an eco-friendly and budget-friendly option. The LUNA-III also offers a Sustainable Package; in addition to the standard starter kit, this package includes the LUNA Reusable Cell Counting Slide as well as Erythrosin B Stain, a safe, non-toxic dye used to assess cell viability. Other accessories include LUNA standard beads for calibration, an external printer, a brightfield validation slide, an IQ/OQ protocol and related consumables.
In addition to automated cell counters, Logos Biosystems also offers a microbial cell counter, cell imaging and tissue clearing systems.
ATA Scientific Pty Ltd www.atascientific.com.au
Frostless ULT freezer range
For those scientists who desire a ULT freezer that doesn’t ice over as frequently and requires less day-to-day maintenance, PHCbi has released its FrostLess ULT freezer range.
FrostLess technology has flipped the conventional idea that insulation should be on the outside. PHCbi has incorporated vacuum insulation panels into the inner doors of the freezer (insulation on the inside), to circumvent the build-up of frost. Less frost means less ice build-up.
A redesign of internal latches reduces the formation of ice on critical locations on the freezer. Improved framework packing and a heated pipe frame around the inner doors suppress frost growth.
Combined frostless technologies reduce associated manual labour and time to defrost by 60%, the company says. In most cases, de-icing frequency is reduced from a weekly requirement to a bimonthly event. Freezer uptime should also be improved, as the impact of ice build-up on wearand-tear and out-of-pocket service costs from unexpected damage is minimised.
Standard features in state-of-the-art compressor technology enhance the user experience, with energy-saving features and environmentally friendly refrigerants to minimise the global effect and costs of ownership.
FrostLess comes in two sizes — 525 and 725 L — with an array of freezer inventory racking configurations to choose from. Bio-Strategy - Part of DKSH Group www.bio-strategy.com
Three-in-one pill
could transform hypertension treatment
New Australian research published in three of the world’s leading medical journals has produced impressive Phase III clinical trial results for an innovative combination of drugs, which could revolutionise the management and treatment of high blood pressure.
Hypertension, or high blood pressure, is the leading preventable cause of heart disease and death. The World Health Organization (WHO) estimates that over 1.2 billion adults have hypertension, with two-thirds living in low- and middle-income countries, and 80% do not have their blood pressure under control. The good news is, every 1 mmHg reduction in systolic blood pressure reduces the risk of major cardiovascular events, such as heart attack and stroke, by approximately 2%.
Data collected from recent trials, conducted across seven countries and diverse populations, has now shown that GMRx2 — a novel, proprietary combination of telmisartan, amlodipine and indapamide developed in ultralow-dose (quarterdose), low-dose (half-dose) and standarddose options — is significantly more effective at controlling blood pressure than standard treatments, while maintaining an excellent safety profile. The polypill originates from a 20-year research program by the Sydney-based George Institute for Global Health, and was developed by spinout company George Medicines.
“This new single-pill combination has the potential to address the critical need for more
effective and tolerable treatment options to achieve and maintain blood pressure control in the many patients who remain uncontrolled on current therapies,” said Dr Paul Whelton, chair of the clinical trial steering committee.
“The findings are particularly noteworthy as they show efficacy at lower blood pressure levels, aligning with the latest guideline recommendations.”
In the largest of the Phase III trials, published in The Lancet, standard and half-dose forms of GMRx2 were tested against dual combinations of its component drugs, involving 1385 patients in Australia, the Czech Republic, New Zealand, Poland, Sri Lanka, the UK and the US. The results indicate that GMRx2 was significantly more effective at controlling blood pressure than the more commonly used dual combinations, highlighting its potential to change people’s lives worldwide.
“The superior efficacy of this triple combination therapy compared to dual combinations, coupled with its good tolerability, addresses key challenges in current hypertension treatment approaches and directly supports recent guideline recommendations,” said Professor Anthony Rodgers, Senior Professorial Fellow at The George Institute and Chief Medical Officer at George Medicines. “Subject to regulatory approval, we believe GMRx2 could play a
crucial role in addressing the global burden of hypertension and improving patient outcomes.”
Trial data published in the Journal of the American College of Cardiology (JACC) showed that GMRx2 triple ¼ and triple ½ doses both delivered significant blood pressure reductions compared to placebo, while data in the Journal of the American Medical Association (JAMA) showed that GMRx2 outperformed a traditional treatment plan that begins with just one drug. Indeed, the JAMA trial — which involved around 300 Black African participants with uncontrolled hypertension in Nigeria — found that the GMRx2 triple combination pill helped 62% of patients control their blood pressure, surpassing the 28% level of control seen with standard care.
“These were certainly the results we were hoping for,” Rodgers said. “It is worth bearing in mind that ‘standard care’ in this trial was much better than average care — even in high-income countries, such good results are rarely seen; it was especially exciting to see the new strategy do even better.”
Brandon Capital, the life sciences venture capital firm, was an early backer in the research and continues to co-invest alongside The George Institute, Federation Private Equity and health insurer Bupa. Dr Stephen Thompson, co-founder and Managing Partner of Brandon Capital, said GMRx2 has the potential to make a significant impact across the world — including in developing countries where access to care is often limited — and that its success highlights the ability of Australian research to address critical global health issues when it receives the necessary investments.
AI-designed DNA switches flip genes on and off
Researchers at The Jackson Laboratory (JAX), Yale University, and the Broad Institute of MIT and Harvard have used artificial intelligence (AI) to design thousands of new DNA switches that can precisely control the expression of a gene in different cell types.
Described in the journal Nature, their approach opens the possibility of controlling when and where genes are expressed in the body, in ways that were never before possible.
In recent years, gene-editing technologies and other gene therapy approaches have given scientists the ability to alter the genes inside living cells. However, affecting genes only in selected cell types or tissues, rather than across an entire organism, has been difficult — in part because of the ongoing challenge of understanding the DNA switches, called cis-regulatory elements (CREs), that control the expression and repression of genes. The researchers managed to design synthetic CREs that can successfully activate genes in brain, liver or blood cells without turning on those genes in other cell types.
“What is special about these synthetically designed elements is that they show remarkable specificity to the target cell type they were designed for,” said Ryan Tewhey, an associate professor at JAX and co-senior author on the work. “This creates the opportunity for us to turn the expression of a gene up or down in just one tissue without affecting the rest of the body.”
Tissue- and time-specific instructions
Although every cell in an organism contains the same genes, not all the genes are needed in every cell, or at all times. CREs help ensure that genes needed in the brain are not used by skin cells, for instance, or that genes required during early development are not activated in adults. CREs themselves are not part of genes, but are separate, regulatory DNA sequences — often located near the genes they control.
Scientists know that there are thousands of different CREs in the human genome, each with slightly different roles. But according to JAX’s Dr Rodrigo Castro, co-first author on the new study, there are “no straightforward rules that control what each CRE does … [which] limits our ability to design gene therapies that only affect certain cell types in the human body”.
Steven Reilly, an assistant professor at Yale and senior author on the study, added, “If we think about it in terms of language, the grammar and syntax of these elements is poorly understood. And so, we tried to build machine learning methods that could learn a more complex code than we could do on our own.”
Using a form of AI called deep learning, the group trained a model using hundreds of thousands of DNA sequences from the human genome that they measured in the laboratory for CRE activity in three types of cells: blood, liver and brain. The AI model allowed the researchers to predict the activity for any sequence from the almost infinite number of possible combinations. By analysing these predictions, the researchers discovered new patterns in the DNA, learning how the grammar of CRE sequences in the DNA impacts how much RNA would be made — a proxy for how much a gene is activated.
The team then developed a platform called CODA (Computational Optimization of DNA Activity), which used their AI model to efficiently design thousands of completely new CREs with requested characteristics, like activating a particular gene in human liver cells but not activating the same gene in human blood or brain cells. Through an iterative combination of ‘wet’ and ‘dry’ investigation, using experimental data to first build and then validate computational models, the researchers refined and improved the program’s ability to predict the biological impact of each CRE and enabled the design of specific CREs never before seen in nature.
“Natural CREs, while plentiful, represent a tiny fraction of possible genetic elements and are constrained in their function by natural selection,” said co-first author Dr Sager Gosai, a postdoctoral fellow at the Broad Institute. “These AI tools have immense potential for designing genetic switches that precisely tune gene expression for novel applications, such as biomanufacturing and therapeutics, that lie outside the scope of evolutionary pressures.”
Pick and choose your organ
The colleagues tested their AI-designed synthetic CREs by adding them into cells and measuring how well they activated genes in the desired cell type, as well as how good they were at avoiding gene expression in other cells. The new CREs, they discovered, were even more cell-type-specific than naturally occurring CREs known to be associated with the cell types.
“The synthetic CREs semantically diverged so far from natural elements that predictions for their effectiveness seemed implausible,” Gosai said. “We initially expected many of the sequences would misbehave inside living cells.”
“It was a thrilling surprise to us just how good CODA was at designing these elements,” Castro added.
Studying why the synthetic CREs were able to outperform naturally occurring CREs, the researchers discovered that their CREs contained combinations of sequences responsible for expressing genes in the target cell types, as well as sequences that repressed or turned off the gene in the other cell types. They also tested several of their CRE sequences in zebrafish and mice, with good results — one CRE, for instance, was able to activate a fluorescent protein in developing zebrafish livers but not in any other areas of the fish.
“This technology paves the way toward the writing of new regulatory elements with pre-defined functions,” Tewhey concluded. “Such tools will be valuable for basic research, but also could have significant biomedical implications where you could use these elements to control gene expression in very specific cell types for therapeutic purposes.”
iStock.com/DKosig
VLP controls for MDx assay performance validation
Meridian introduces VLP-RNA Extraction Controls — a solution to monitor the extraction, reverse-transcription and amplification processes with a single, customisable control. Designed to integrate seamlessly with assay primers, the controls provide a straightforward and effective method to reduce false negative results in RT-qPCR assays. By applying VLP controls, users can achieve comprehensive performance validation across each stage of a molecular diagnostic (MDx) assay.
Meridian says that its VLP-RNA Extraction Controls consist of virus-like particle (VLP) shells, meticulously packaged with precise quantities of target RNA molecules. This biomimetic composition closely mimics a test sample, offering a full-process control that oversees the entire RT-qPCR assay workflow, from lysis and extraction to reverse transcription and amplification.
The innovative product is particularly beneficial for ensuring the accuracy of RT-qPCR assays, the company says. By closely monitoring each step of the process, VLP-RNA Extraction Controls help identify potential issues that could lead to false negatives, thereby enhancing the robustness and credibility of the results.
Designed to oversee the quality of the sample lysis step, the controls also maintain RNA stability in the presence of nucleases commonly found in biofluids. This means the integrity of the RNA is preserved throughout the assay, providing consistent data.
Meridian’s VLP-RNA Extraction Controls are crafted to deliver precise and dependable results for molecular in vitro diagnostics. The company’s knowledgeable tech support team is readily available to assist with any product or application-related inquiries. Millennium Science Pty Ltd
Upgraded microfluidic system
Refeyn has introduced a next-generation microfluidic chip and other improvements to its MassFluidix HC microfluidic system, in order to enhance the rapid dilution of highly concentrated samples and improve insight into low-affinity and transient biomo lecular interactions. The updates are designed to save users time while enabling reproducibility across experiments and labs and supporting a broader range of applications.
A key addition to the system is a second-generation microfluidic chip which enables mass photometry measurements in five channels and features even faster sample dilution — in less than 37 ms. Usage is simplified with a channel redesign that removes the need for a bubble trap and introduces luer connectors that enable easy connection of tubing to the chip. The ready-to-use chip is individually packaged, allowing users to open just one at a time as needed.
Further improving ease of use, software integration now means that the rapid dilution system can be readily operated directly via Refeyn’s Acquire MP mass photometer control software. An automatic microfluidic chip channel detection feature within this software also simplifies workflows by guiding correct positioning of the chip for each measurement.
The upgraded system’s rapid dilution allows the characterisation of samples at high concentration. This is particularly useful as a quality check for techniques that require higher concentrations, such as cryoEM and crystallography, as well as for detecting and determining stoichiometry for weak affinity protein-protein interactions. This has implications for traditionally difficult-to-characterise sample types, such as PROTACs and multi-component complexes; in addition to more common applications, such as antibody-receptor binding, and as an orthogonal technique to other binding characterisation techniques.
NewSpec Pty Ltd www.newspec.com.au
Mouse immunoprofiling in a single tube
The Cytek 24-Color Mouse Immunoprofiling Panel is Cytek’s latest preoptimised, High Parameter Enabler (HPE) reagent panel that allows for comprehensive mouse immunophenotyping. It enables users to enhance their immunoprofiling protocols with an easy-to-implement, single-tube assay for identification of over 20 mouse immune subpopulations.
Multiparametric flow cytometry is a powerful and versatile technique widely used in mouse research. By using HPE reagents, the panel enables users to efficiently identify and characterise multiple lineage subsets in single-cell suspensions of mouse tissue.
Cytek’s pre-optimised reagent kits and panels enable users to leave behind time-consuming, labour-intensive, costly panel design and optimisation. These expertly designed solutions have been meticulously developed by Cytek scientists and come with protocols and experiment templates to help streamline workflow.
Sapphire Bioscience www.sapphirebioscience.com
Delving deeper into CAR T cell evaluation
A 3D imaging workflow to study the infiltration potential of CAR T cells into solid tumors
Profound analysis of tumor physiology and distribution of anti-tumor CAR T cells in the tumor microenvironment (TME) requires comprehensive 3D imaging data. Common 2D histological and IHC microscopy techniques are not sufficient for this purpose as they are usually applied to a limited number of thin sections, which leads to the potential risk of missing relevant information.
Tissue clearing, combined with light sheet microscopy, has the potential to bridge this technological gap and enable single-cell resolution imaging of whole large samples, including solid tumors or even entire organisms. However, technically challenging instruments and the use of homemade, difficult-toreproduce immunostaining and clearing protocols currently pose significant obstacles to the establishment of this workflow in the context of pre-clinical studies.
In this article, we showcase the efficacy of 3D fluorescence microscopy using the UltraMicroscope Blaze™ for analyzing CAR T cells in solid tumors, employing pancreatic carcinoma xenografts as a model. By using automated light sheet microscopy along with validated antibodies, straightforward tissue clearing, and immunolabeling protocols, we can visualize and quantify multiple tumor
parameters and the infiltration of therapeutic CAR T cells at a cellular level. Hence, this workflow facilitates the unbiased evaluation of cellular therapies in large, heterogeneous samples like solid tumors and the TME.
In light sheet microscopy, the optical pathways for fluorescence excitation (horizontal) and detection (vertical) are decoupled. A laser light sheet is directed perpendicular to the observation axis, selectively exciting a single plane of the labeled sample. Illuminating only a thin layer along the z-axis produces highresolution images with minimal and strictly localized photodamage and bleaching effects, unlike traditional epifluorescence microscopy techniques. By moving the sample along the z-axis through the light sheet, a series of images can be generated, forming a stack that enables the visualization of large biological samples in 3D with single-cell resolution. Imaged samples can range from small organoids and rodent organs to larger entities like whole mouse models or human kidneys.
3D light sheet imaging offers a valuable alternative to traditional histology and microscopy techniques in preclinical screenings, addressing the challenges associated with evaluating complex 3D samples such as solid tumors and their microenvironment.
• Implementing the 3D imaging workflow in CAR T cell evaluation results in cost and time savings by providing researchers an unbiased, reliable tool to identify the best therapeutic CAR T cell candidates against solid tumors and discard less effective cell lines as early as possible.
• Light sheet microscopy is a versatile imaging technique applicable to various cell types and research areas, from CAR T cells to blood vessels, from immunooncology to neuroscience.
• Our user-friendly 3D imaging workflow and fully automated UltraMicroscope Blaze overcomes concerns about laborious protocols and complex instruments, making 3D light sheet imaging accessible and reproducible to everyone.
For all the details on this collaboration, please use the QR code
Miltenyi Biotec Australia Pty Ltd www.miltenyibiotec.com
Pancreatic carcinoma, imaged using a light sheet microscope.
Meditation to reduce pain is more than a placebo
Mindfulness meditation, which has long been used for pain management in various cultures, has been speculated to work by activating processes supporting the placebo response — however, US scientists have now shown that this is not the case.
The placebo effect, or tendency for a person’s symptoms to improve in response to inactive treatment, is a well-known example of how expectations can significantly alter a person’s experience. But according to the new study, which was published in the journal Biological Psychiatry, mindfulness meditation engages distinct brain mechanisms to reduce pain, compared to those of the placebo response.
The study included 115 healthy participants and consisted of two separate clinical trials. Participants were randomly placed into groups to receive four interventions: a mindfulness meditation that was practiced by focusing on the breath without judgement; a sham-mindfulness meditation that only consisted of deep breathing; a placebo cream (petroleum jelly) that participants were trained to believe reduces pain; and listening to an audiobook (control group). The researchers applied a painful but harmless heat stimulus to the back of the leg and scanned the participants’ brains while they received their respective interventions.
To analyse the participants’ brain activity patterns, the researchers used functional MRI and a novel approach called multivariate pattern analysis (MVPA) — developed by study co-author Dr Tor D Wager, from Dartmouth College — which uses machine learning to disentangle the many complex neural mechanisms underlying the experience of pain, including those stemming from specific heat stimulus, negative emotions and pain responses that are driven by the placebo effect. The researchers were then able to identify if mindfulness meditation and placebo engage similar and/ or separate brain processes.
Although placebo cream and sham-mindfulness meditation lowered pain, the researchers found that mindfulness meditation was significantly more effective at reducing pain when compared to placebo cream, shammindfulness meditation and the controls.
“It has long been assumed that the placebo effect overlaps with brain mechanisms triggered by active treatments, such as mindfulness meditation,
but these results suggest that when it comes to pain, this may not be the case,” said lead investigator Dr Fadel Zeidan, from the University of California San Diego. “Instead, these two brain responses are completely distinct, which supports the use of mindfulness meditation as a direct intervention for chronic pain rather than as a way to engage the placebo effect.
“The mind is extremely powerful, and we’re still working to understand how it can be harnessed for pain management by studying the brain. By separating pain from the self and relinquishing evaluative judgment, mindfulness meditation is able to directly modify how we experience pain in a way that uses no drugs, costs nothing and can be practised anywhere.”
The researchers also found that mindfulness-based pain relief reduced synchronisation between brain areas involved in introspection, self-awareness and emotional regulation. These parts of the brain together comprise the neural pain signal (NPS), a pattern of brain activity thought to be common to pain across different individuals and different types of pain. In contrast, the placebo cream and sham-mindfulness meditation did not show a significant change in the NPS when compared to controls. Instead, these other interventions engaged entirely separate brain mechanisms with little overlap.
In modern medicine, new therapies are generally deemed effective and reliable if they outperform placebo. Since the present study found that mindfulness meditation is more powerful than placebo and does not engage in the same neurobiological processes as placebo, the findings have important implications for the development of new treatments for chronic pain. However, it will take more research to demonstrate these effects in people living with chronic pain as opposed to healthy participants.
In the long term, the researchers hope that by understanding the distinct brain mechanisms underlying mindfulness meditation, they can design more effective and accessible interventions that harness the power of mindfulness to reduce pain in people with various health conditions.
“Millions of people are living with chronic pain every day, and there may be more these people can do to reduce their pain and improve their quality of life than we previously understood,” Zeidan concluded. “We are excited to continue exploring the neurobiology of mindfulness and how we can leverage this ancient practice in the clinic.”
Automated cell culture system
Molecular Devices’ CellXpress.ai Automated Cell Culture System is an approachable, hands-off automated solution built by scientists, for scientists. It has been built for continuous operation, so the user never has to worry about missing a feeding or passaging step.
The cell culture system provides workflow repeatability through automation and applies imaging-guided AI decisionmaking so that cell culture feeding and passaging events happen at the right time, while event alerts keep users informed of their cell culture status. Users can automate the entire cell culture process to improve workflows and make assays more reproducible.
The system is an AI-driven cell culture innovation hub that gives teams total control over demanding cell culture feeding and passaging schedules, eliminating time in the lab while maintaining a 24/7 schedule for growing and scaling multiple stem cell lines, spheroids or organoids. It can give labs the confidence in experimental outcomes to make key decisions sooner, achieve milestones faster and get to clinic earlier — with low attrition rates. It is backed by a full event log to confirm on-time feedings and critical task execution with complete digital microscopy records.
Bio-Strategy - Part of DKSH Group www.bio-strategy.com
High-throughput cytometry handbook
Sartorius has published its Second Edition High-Throughput Screening by Cytometry Handbook, designed to empower both new and seasoned flow cytometry users who are curious about the capabilities of HTS cytometry. Those using traditional systems will learn how routine workflows can benefit from the speed, throughput and ease of use offered by the iQue HTS by Cytometry Platform. Labs already familiar with the platform can learn about new reagents, assay kits and software releases. Importantly, the handbook features the latest Sartorius publications, so readers can stay up to date on the latest applications with HTS by cytometry in both popular and emerging fields.
Flow cytometry technology continues to evolve to meet the needs of labs developing next-generation therapeutics. The iQue platform is designed to meet this growing demand for speed and efficiency. In the handbook, readers can easily navigate topics of interest, including informative workflow illustrations, detailed application examples and direct links to external resources for further learning. Chapters highlight iQue HTS applications in Cell Health, Secreted Proteins, Cell Line Development, Biologics Discovery, Immune Cell Models and Cell Therapies, with sections on new antibody modalities and advanced cell models, like stem cells and organoids.
This edition also features an in-depth discussion of the integrated iQue Forecyt software, which replaces the multiple data analysis packages typically required in other protocols. Its real-time data visualisation, smart gating, plate-level analytics and other advanced tools are further illustrated throughout the handbook.
Sartorius Australia Pty Ltd www.sartorius.com
Low gravity disrupts normal rhythm in heart muscle cells
Johns Hopkins Medicine scientists who arranged for 48 human bioengineered heart tissue samples to spend 30 days at the International Space Station have reported that the low-gravity conditions in space weakened the tissues and disrupted their normal rhythmic beats when compared to Earth-bound samples from the same source.
The scientists said the heart tissues don’t fare well in space and that, over time, the tissues aboard the space station beat about half as strong as tissues from the same source kept on Earth. Their findings, published in Proceedings of the National Academy of Sciences, expand scientists’ knowledge of low gravity’s potential effects on astronauts’ survival and health during long space missions, and may serve as models for studying heart muscle aging and therapeutics on Earth.
Previous studies showed that some astronauts return to Earth from outer space with age-related conditions, including reduced heart muscle function and arrhythmias (irregular heartbeats), and that some, but not all, effects dissipate over time after their return. But scientists have sought ways to study such effects at a cellular and molecular level in a bid to find ways to keep astronauts safe during long spaceflights, said Johns Hopkins Professor Deok-Ho Kim, who led the project to send heart tissue to the space station.
To create the cardiac payload, scientist Dr Jonathan Tsui coaxed human induced pluripotent stem cells (iPSCs) to develop into heart muscle
cells (cardiomyocytes). Tsui then placed the tissues in a bioengineered, miniaturised tissue chip that strings the tissues between two posts to collect data about how the tissues beat (contract). The cells’ 3D housing was designed to mimic the environment of an adult human heart in a chamber half the size of a mobile phone.
To get the tissues aboard the SpaceX CRS-20 mission, which launched in March 2020 bound for the space station, Tsui had to hand-carry the tissue chambers on a plane to Florida, and continue caring for the tissues for a month at the Kennedy Space Center. Once they were on the space station, the scientists received real-time data for 10 seconds every 30 minutes about the cells’ strength of contraction, known as twitch forces, and on any irregular beating patterns. Astronaut Dr Jessica Meir changed the liquid nutrients surrounding the tissues once each week and preserved tissues at specific intervals for later gene readout and imaging analyses.
The research team kept a set of cardiac tissues developed the same way on Earth, housed in
In addition to losing strength, the heart muscle tissues in space developed arrhythmias — disruptions that can cause a human heart to fail.
the same type of chamber, for comparison with the tissues in space. When the tissue chambers returned to Earth, Tsui continued to maintain and collect data from the tissues. Dr Devin Mair, a postdoctoral fellow at Johns Hopkins, then analysed the tissues’ ability to contract.
In addition to losing strength, the heart muscle tissues in space developed arrhythmias — disruptions that can cause a human heart to fail. Normally, the time between one beat of cardiac tissue and the next is about a second. This measure, in the tissues aboard the space station, grew to be nearly five times longer than those on Earth, although the time between beats returned nearly to normal when the tissues returned to Earth.
The scientists also found, in the tissues that went to space, that sarcomeres — the protein bundles in muscle cells that help them contract — became shorter and more disordered, a hallmark of human heart disease. In addition, energyproducing mitochondria in the space-bound cells grew larger, rounder and lost the characteristic
DNA-barcoded antibody human discovery panel
The MultiPro Human Discovery Panel, from Proteintech Genomics, is built on 10x Genomics’ Chromium Single Cell Gene Expression Flex chemistry with Feature Barcode technology, allowing researchers to explore proteins located both within the intracellular compartments and on the surface of cells. This makes it possible to conduct comprehensive multiomic analyses and attain deep insights into cellular responses, functional states, drug target response and protein signalling networks.
Consisting of 346 antibodies against 325 distinct proteins, the panel offers significant coverage of key cellular components, including transcription factors, cytokines, signalling proteins and phospho-epitopes. Importantly, two-thirds of these protein targets are intracellular, while the remaining third are located on the cell surface.
Available as panels or single antibodies to provide flexibility in experimental design, the product is compatible with the 10x Genomics Chromium Single Cell Gene Expression Flex workflow. United Bioresearch Products Pty Ltd www.unitedbioresearch.com.au
folds that help the cells use and produce energy.
Finally, the scientists studied the gene readout in the tissues housed in space and on Earth. The tissues at the space station showed increased gene production involved in inflammation and oxidative damage, also hallmarks of heart disease.
“Many of these markers of oxidative damage and inflammation are consistently demonstrated in post flight checks of astronauts,” Mair said.
Kim’s lab sent a second batch of 3D-engineered heart tissues to the space station in 2023 to screen for drugs that may protect the cells from the effects of low gravity. This study is ongoing, and according to the scientists, these same drugs may help people maintain heart function as they get older.
The scientists are continuing to improve their ‘tissue on a chip’ system and are studying effects of radiation on heart tissues at the NASA Space Radiation Laboratory. The space station is in low Earth orbit, where the planet’s magnetic field shields occupants from most of the effects of space radiation.
AAV vector characterisation kit
Bio-Rad Laboratories has launched its Vericheck ddPCR Empty-Full Capsid Kit for the determination of capsid titre, genome titre and percentage of full capsids in purified or unpurified (crude lysate) AAV samples.
AAV vectors are a powerful gene therapy tool, but their production can result in the generation of product-related impurities, such as partial or empty capsids, which impact effectiveness and can elicit unwanted immunotoxicity. Determining the ratio of full, partial and empty capsids is a recurring challenge throughout AAV gene therapy manufacturing, from early-stage development to quality control and release testing.
The kit is designed to deliver precision and specificity, along with ease of use and high-throughput capabilities, to provide users with a comprehensive solution for AAV vector characterisation and to help drive the advancement of safe and effective gene therapies. Using Bio-Rad’s Droplet Digital PCR technology, it analyses minimal amounts of either crude lysate or purified samples to deliver robust, reproducible data for assessment of AAV vector quality.
Designed for use on the company’s Droplet Digital PCR Systems, the kit enables optimisation of AAV vector characterisation processes to streamline gene therapy development and production while supporting compliance with regulatory guidelines.
Bio-Rad Laboratories Pty Ltd www.bio-rad.com
NGS profiling system
Takara Bio Europe’s Shasta Single-Cell System is a cutting-edge, high-throughput NGS solution that enables novel biomarker discovery in oncology research. The comprehensive system combines well-validated chemistries with user-friendly bioinformatics tools, which should allow researchers to mine more genomic and transcriptomic information from a greater number of cells than previously possible.
Together, the Shasta system and Shasta Whole-Genome Amplification (WGA) Kit can increase throughput for WGA by processing up to 1500 cells per run, while current technologies are limited to 384 single cells, and enable the detection of single-cell level CNV events via shallow sequencing. The Shasta Total RNA-Seq Kit, a high-throughput single-cell total RNA profiling kit, meanwhile offers full gene body coverage of up to 100,000 cells per run.
Scientifix Pty Ltd www.scientifix.com.au
Static elimination in sensitive processes
EXAIR’s Intellistat Ion Air Gun is a handheld and lightweight solution for static elimination in clean processes, electronic test facilities, laboratories and cleanrooms. Rated Class 5 for ISO 14644-1 and controlled environments, the product has secured a patent highlighting its design and operation that represents EXAIR’s advancement in cleanroom static elimination.
The device is designed to consume minimal compressed air while simultaneously delivering precise blow-off and good static decay rates. Intended for cleanrooms and processes sensitive to particulate or static, it produces clean, ionised airflow for removing troubling dust or static charges without compromising production.
Made from durable static dissipative polycarbonate, the product is useful for applications requiring non-conductivity, such as circuit board or electronics manufacturing, as well as blowoff applications like cleaning lenses or removing debris from medical products. It also features LED lights to enable proper functionality and a lightweight frame for prolonged use. It is low maintenance, UL listed and CE compliant.
Compressed Air Australia Pty Ltd www.caasafety.com.au
Sensitivegas measurement with a new s pectroscopy technique
Scientists at the US National Institute of Standards and Technology (NIST) have developed a new laserbased technique that could dramatically improve our ability to analyse a variety of materials and gases, including greenhouse gases. The new method, called ‘free-form dual-comb spectroscopy’, offers a faster, more flexible and more sensitive way to analyse substances in the air and other materials.
In a study published in the journal Nature Photonics, the researchers have now demonstrated that their laboratory-based system can detect a single gas, in this case the potent greenhouse gas methane, with 22 times higher sensitivity than a traditional dual-comb system. This increased sensitivity could one day help identify small leaks or emissions that might otherwise go unnoticed, potentially aiding in efforts to combat climate change.
Technological advancements
Spectroscopy is a sophisticated technique that allows scientists to identify and measure different materials by observing how they interact with light. Just as a prism separates white light into a rainbow of colours, spectroscopy separates the light coming from or passing through a substance, revealing its unique ‘fingerprint’ and providing valuable information about its properties and composition.
The NIST researchers have created an improved version of a laser-based measurement technique called dual-comb spectroscopy. Dual-comb spectroscopy is a particularly highresolution form of spectroscopy that allows many colours of light to be examined at the same time and in fine detail.
The new laser measurement technique improves on older methods by allowing scientists to control the timing of laser pulses with incredible precision. This precise control lets them focus on the most important parts of a sample’s fingerprint and ignore areas that don’t provide useful information. As a result, the smarter system can detect and measure substances much faster than before.
This new approach can be used in several ways. For example, scientists can use it to quickly create images showing how the gas is distributed in space. Alternatively, if researchers don’t know exactly what kind of gas is in the area they are investigating, they can use a generic technique called compressive sampling. This is a ‘smart’
method of making measurements, concentrating on areas likely to have important information and taking fewer measurements elsewhere. This strategy makes the whole process 10 to 100 times more efficient than traditional methods.
In the new study, researchers created real-time images of methane plumes, which wasn’t possible previously. Methane is a potent greenhouse gas that contributes to climate change, so being able to detect and address these leaks efficiently could one day help protect the environment and improve air quality. By quickly generating images of methane plumes, scientists could quickly identify where gas is escaping. Indeed, the technique is useful not only for detecting greenhouse gases but for any situation in which scientists need to identify and measure gases.
Two lasers are better than one The heart of free-form dual-comb spectroscopy lies in the Nobel Prize-winning optical frequency comb — a laser tool that produces light at a series of equally spaced, precise frequencies that resemble the teeth of a comb. These frequency combs are used for a variety of purposes, from precision timekeeping to medical diagnostics and even the search for elusive dark matter.
The ‘dual-comb’ aspect of this technology refers to the use of two optical frequency combs working together. This approach enables rapid, precise measurements of substances by analysing how they interact with the light from both combs. This technique is much faster than a single comb and can provide more detailed information than many traditional spectroscopy methods.
Acid digestion fume hood
‘Free-form’ refers to the flexibility in highly precise frequency comb control that has recently become possible. The frequency combs emit light pulses that are just 100 femtoseconds in duration. Inside each of these brief light bursts, there’s an electric field that vibrates extremely rapidly, millions of millions of times per second. The ability to quickly and accurately control this fast light allows researchers to improve and adjust how they take measurements.
Dual-comb’s next big leap
By enabling smarter detection of gases and other substances, this innovative laser technology could
play a crucial role in protecting both public health and the environment in the years to come. The researchers plan to continue improving their system in the laboratory, making it even faster and adapting their approach to work with a wide range of laser wavelengths.
“The flexibility of our system means it could be adapted for a wide range of applications,” said NIST researcher Esther Baumann. “In the future, we might see more versatile and efficient sensors based on this technology in everything from air quality monitors to food safety detectors to studying how materials burn or assessing muscle health non-invasively.”
The UniFlow HDPE Acid Digestion Fume Hood is engineered specifically for corrosive operations involving dissolution procedures for element analysis. The unit features a chemical-resistant hood construction with a welded one-piece HDPE interior fume chamber including hood walls, ceiling, work surface and rear drain trough. The exterior is also chemical resistant, being constructed of composite resin.
Available in 122, 152, 183 and 244 cm models, the fume hood can be supplied with or without a built-in washdown system and rear drain trough. It includes a counterbalanced vertical sliding clear viewing sash in either polycarbonate or tempered glass (depending on whether hydrofluoric acid is being used); vapourproof LED light fixture; pre-wired switch; and remote-control water fixture with built-in spray nozzles if washdown is required.
A wide selection of factory-installed accessories, support cabinets/tables and ventilation equipment are offered to meet the user’s exact requirements.
HEMCO Corporation www.hemcocorp.com
Esther Baumann and her colleagues at NIST developed the improved version of dual-comb spectroscopy.
SaaS LIMS
The Xybion LIMS 10.0 builds on over 200 customer implementations and the knowledge and experience of Autoscribe Informatics in LIMS and ELN software, combined with Xybion’s 40+ years of experience in building life sciences SaaS R&D LIMS and QMS software.
The LIMS presents users with a modern look and feel that provides an intuitive and user-friendly digital workspace with streamlined navigation and improved accessibility. The platform is integrated with a powerful Xybion QMS system, allowing companies to rapidly digitise laboratory processes, accelerate tests and study timelines, while enabling full compliance with 21 CFR Part 11 requirements and various global regulatory agencies including US FDA, EMA, Eudra and TGA.
The LIMS is fully functional out of the box, with the flexibility for easy configuration by users. It offers configurable solutions for various industries and functions, including life sciences, manufacturing, oil and gas, water testing, veterinary science, environmental, biobank management and stability studies. Systems are integrated to meet specific industry needs, underscoring Xybion’s commitment to delivering configured bespoke solutions.
The comprehensive, fully featured LIMS supports complex laboratory workflows and sample management as well as providing additional functionality required for running integrated laboratory operations, including instrument calibration and maintenance; inventory management; competency management; storage management; chain of custody and full audit trail; runsheets and QC samples; CAPA management; and controlled document management.
The sophisticated software architecture supports seamless upgrades that easily maintain existing functionalities, therefore reducing the need for manual intervention and increasing efficiency. A plate management solution has also been introduced, allowing for the management of 96-well plates and similar configurations.
The advanced Bioanalytical System includes additional statistical calculations and data processing functions to support complex workflows. Integration into Xybion’s existing comprehensive suite of solutions meanwhile offers further improved functionality and efficiencies. Autoscribe Informatics Pty Ltd www.autoscribeinformatics.com.au
Automatic exosome isolation system for high speed, purity and yield
The EXODUS series of automatic exosome isolation systems represents an advanced technological approach for laboratories engaged in extracellular vesicle (EV) research, particularly those focused on exosomes.
Exosomes — nanometre-scale EVs with key roles in cell–cell communication — have gained prominence due to their potential as biomarkers for disease diagnostics and as vehicles for therapeutic delivery. But traditional methods for exosome isolation — such as ultracentrifugation, precipitation and size-exclusion chromatography — are labour-intensive and pose multiple challenges, including low yield, variable purity and susceptibility to sample degradation, which limit reproducibility and scalability.
The EXODUS BIO automatic exosome isolation system is designed to minimise manual handling, reducing variability and enabling consistent, high-purity yields across a range of biological fluids, including serum, plasma, urine and cell culture media. This facilitates the preservation of exosomal structural integrity of bioactive molecules, which is important for downstream applications including molecular profiling and drug delivery studies.
The EXODUS has been developed using a dual-membrane nanofiltration system that integrates periodic negative pressure oscillation (NPO) and double-coupled ultrasonic harmonic oscillations (HO). The exosomes are intercepted by a nanoporous membrane, while free nucleic acid and protein impurities are removed from the sample, resulting in the efficient purification and enrichment of exosomes.
The product is suitable for labs aiming to scale up exosome research while maintaining rigorous standards in quality and reproducibility. It eliminates challenges associated with traditional ultracentrifugation, making exosome isolation more accessible and efficient. Researchers can thus expect enhanced workflow efficiency and the capacity to drive new discoveries in the rapidly expanding field of EV research.
ATA Scientific Pty Ltd www.atascientific.com.au
A science-based solution for tackling lake health
Experts urge moving away from short-term ‘fixes’ that only worsen a lake’s condition over time, and instead advocate for a holistic, science-based strategy that tackles the underlying causes of lake health to revitalise the entire ecosystem.
Lakes are more than just bodies of water; they are vital ecosystems that support diverse life forms, provide recreational enjoyment and sustain local economies. Yet, across the US, these precious resources are under threat.
The water quality in lakes is declining at an alarming rate, leading to severe repercussions. Observable indicators of this deterioration include the emergence of symptoms such as invasive weeds, algae blooms, the emission of unpleasant odours and ‘fish kills’.
When a crisis occurs, specialists are called in to evaluate and oversee the situation. Diagnostic tests are performed to confirm the presence of a harmful algae bloom (HAB) — a fact that usually is already evident. Frequently, the application of chemicals like biocides is advised.
While the notion of eradicating algae to improve the lake’s appearance before an upcoming holiday is enticing, this can lead to a detrimental cycle that accelerates the deterioration of the lake’s ecosystem.
The elimination of algae results in the release of toxins, leading to the destruction of more beneficial organisms and favouring the proliferation and dominance of the harmful organisms in the lake. Over time, the continued application of algaecides causes lake algae blooms to worsen. In other words, the symptoms are treated temporarily, but the patient never gets better.
The US Government Accountability Office (GAO) has confirmed the severity of this issue. The findings are clear: we are losing the battle to protect our lakes, and unless we change our approach, the situation will continue to deteriorate. As a result, many experts are urging a different approach and a more permanent solution.
“The goal should be to reverse the damage and restore these vital ecosystems, but to do so, we must revise and sometimes abandon practices of the past that have been widely recognised to be ineffective and embrace a new way of managing our lakes — one that is proactive, science-based
and focused on addressing the root causes of degradation,” said Dr Wayne Carmichael, a prominent expert in aquatic toxicology, known for his work on toxic cyanobacteria.
Carmichael has over 500 peer-reviewed papers, publications and presentations, and has consulted on cyanobacteria issues in over 25 countries. He advises federal, state and local agencies, participates in national and international committees, and has contributed to reports for the World Health Organization.
Fortunately, there are effective, comprehensive solutions that can help in the fight to save our lakes. The solution is a multifaceted approach that addresses the root causes of water quality degradation. Ultimately, this approach can improve water quality, enhance recreational opportunities and preserve aquatic ecosystems for future generations.
The root causes of lake deterioration
The decline in lake health is driven by several interconnected factors, described in general as eutrophication. Eutrophication is the technical term for the process that occurs when water bodies become overly enriched with nutrients, resulting in sediment nutrient accumulation.
These nutrients are recycled back into the water, fuelling further algae growth and creating a feedback loop that perpetuates the cycle of degradation. A tipping point is eventually reached when sediment nutrient recycling is sufficient to sustain eutrophic conditions and facilitate a switch to cyanobacteria dominance. In short, HABs become more prevalent, persistent and intense.
According to Carmichael, the cause of eutrophication is well established. While some levels of nutrients are natural, human activities such as agriculture and urban runoff have accelerated eutrophication to dangerous levels, overwhelming nature’s capacity to clear out these nutrients and maintain balance. Whether caused by climate change or not, the water temperature of lakes is increasing, further fuelling eutrophication.
Clean-Flo International
Unfortunately, many lake management strategies often prove inadequate because they target the symptoms rather than the root cause factors that drive eutrophication in lakes.
In search of more permanent solutions
According to Carmichael, effective restoration of lake and water reservoir health begins with monitoring key metrics that go beyond confirming the poor condition of the lake. These metrics should assess the entire ecosystem and provide indicators that can be used to evaluate sustained improvement.
“[As an agency and industry] we have done a good job of monitoring, but now we need to get more serious about remediation and prevention,” Carmichael said.
This does not include simply applying air, flocculating/binding agents or algaecides as a quick fix. Treating the symptoms in this way often causes a rebound effect, where the underlying issues become more severe over time.
“Chemical and physical methods either dampen the effects of a bloom or shorten the bloom, but do not prevent the bloom,” said Carmichael, who notes that the net effect is often only to temporarily improve lake conditions for a few weeks or months.
The truth is that in most cases biocides, whether herbicides or algaecides, only make the problem worse. Algaecides are more effective against beneficial algae than cyanobacteria, and cyanobacteria are better able to recover after each application.
By killing algae and cyanobacteria cells, toxins are also released, and the dead cells sink to the bottom and compound nutrient recycling when they decompose. As algae die and decompose, oxygen is consumed in the water, leading to hypoxic conditions — ‘dead zones’ where aquatic life cannot survive. Hypoxia is a major driver of fish kills and the loss of biodiversity in lakes.
Addressing the root cause, therefore, means properly managing sediment accumulation.
“In most cases, the nutrients become part of the sediment, which becomes part of the permanent morphology of the lake,” Carmichael said.
An important first step is to identify methods that recycle properly in a natural way those nutrient-rich sediments without “just physically removing and dumping them somewhere [through dredging techniques] but allowing them to be used in the lake ecosystem because nutrients are needed for organisms to grow”, Carmichael said.
“Most of the nutrients are organic and can be recycled back through the food web to benefit the natural cycle of the lake — not the HAB cycle of the lake,” he added.
Addressing hypoxia by ensuring adequate oxygen levels in the water is also crucial for maintaining a healthy lake ecosystem. Although there are many different solutions that can be used to help revive a lake ecosystem, one promising category involves utilising Rapid Acting Dissolved Oxygen Restoration (RADOR) technology. Numerous studies have demonstrated that high, stable oxygen levels reduce nutrients and minerals in the water column and can keep phosphorus locked into the organic sediments.
“RADOR helps ensure that the necessary increase in oxygen levels is properly maintained throughout the entire water column within a lake,” said Dave Shackleton, President of Clean-Flo International — a US-based leader in biological water management solutions for managing water quality in biological environments such as wastewater treatment, rivers, lakes and reservoirs.
“By increasing dissolved oxygen levels throughout the water column, the RADOR system initiates a sequence of events that bio-dredge mucky sediment, control aquatic weeds, improve water quality, [and] reduce organic muck, nutrients, odour, harmful gases and coliform bacteria. This helps to restore the nutrient clearing capacity of the food web by improving fish growth and health,” Shackleton explained.
Clean-Flo designs its RADOR systems using compressors of various sizes based on the lake and application, along with self-sinking airline and diffusers that maintain full oxygenation from the bottom to the surface of the water.
“Another important step in restoring balance to a lake is bioaugmentation, which involves the use of enzymes to break down organic muck, like a compost pile. Boosted by natural enzymes, aerobic bacteria and microorganisms consume the organic muck and nutrients, while aquatic insects feed on the bacteria, increasing the natural food source for fish,” Shackleton said.
Critical micronutrients can also be introduced to stimulate the growth of organisms that form the foundation of a productive food web. This enables balance to be restored at the level of phytoplankton, so that beneficial algae can outcompete the toxic cyanobacteria, preventing HABs and providing better nutrition for the food web. The food web becomes more productive so that nutrient clearance is restored and sediment nutrient stockpiles are depleted as they are bio-dredged away.
Consistent use of these products over time reduces nutrient availability and helps maintain clean, healthy water. As water quality improves, swimming conditions get safer. The reduction of organic sediments helps control aquatic weeds by minimising the nutrient-rich rooting bed that mucky sediment provides for their growth.
According to Shackleton, these are only a few of the available solutions, and customised programs based on the specific conditions of each lake are typically required to ensure restoration and long-term lake health.
“To preserve our nation’s lakes, the industry must adopt a new approach to lake management — one that supports nature and addresses the root causes of degradation,” Shackleton said. “Working with nature, rather than against it, is key to restoring lake health.”
iStock.com/Willard
event horizon
Science Meets Parliament 2025
February 12–13, Canberra
Science Meets Parliament is Australia’s premier initiative for fostering meaningful connections between the STEM sector and policymakers, celebrating its 25th anniversary in 2025.
The event features a comprehensive training program designed to strengthen relationships between federal parliamentarians and professionals in science and technology. Participants gain valuable insights into effective engagement strategies with policymakers, while parliamentarians have the opportunity to connect with leading experts in science and technology. The national gathering brings together STEM leaders for expert-led professional development, a welcome reception, a parliamentary forum, a national gala dinner, a televised address at the National Press Club, and intimate meetings with parliamentarians in small group settings. STEM professionals with an interest in broadening their networks and learning how to engage effectively with policymakers are encouraged to attend the event. scienceandtechnologyaustralia.org.au/science-meets-parliament/
The 47th Annual Condensed Matter and Materials Meeting
February 4–7, Brisbane www.aip.org.au/CMM-Conference
Lorne Proteins 2025 February 9–13, Lorne www.lorneproteins.org
Lorne Cancer 2025
February 13–15, Lorne www.lornecancer.org
Lorne Genome 2025 February 16–19, Lorne www.lornegenome.org
Lorne Infection & Immunity 2025 February 19–21, Lorne www.lorneinfectionimmunity.org
Pathology Update 2025 February 21–23, Melbourne www.rcpa.edu.au/Events/Pathology-Update
2025 Food Microbiology Conference
March 5–6, Sydney www.aifst.asn.au/AIFST-2025-Food-MicroConference
Australian Healthcare Week 2025 March 19–20, Sydney www.ahwdigital.com.au/events-austhealthweek
TSANZSRS 2025
March 21–25, Adelaide tsanzsrsasm.com
World Science Festival Brisbane 2025 March 21–30, Brisbane www.worldsciencefestival.com.au/2025-eventprogram
Quantum Australia Conference 2025
March 25–27, Brisbane www.lsq.com.au/events/2025-quantum-australiaconference
ASID Annual Scientific Meeting 2025
April 3–5, Canberra www.asidasm.com
AusMedtechInvest 2025
May 6, Sydney www.ausbiotechinvestment.com.au/aboutausmedtechinvest
AusMedtech 2025 May 7–8, Sydney www.ausmedtech.com.au
AUS-oMicS 2025
May 18–21, Cairns www.ausomics.com
15th International Nanomedicine Conference
June 16–18, Sydney www.oznanomed.org
ASM National Meeting 2025 July 14–17, Adelaide www.theasmmeeting.org.au
Accreditation Matters 2025 July 30–31, Sydney nata.com.au/events/accreditation-matters-2025/
National Science Week 2025 August 9–17, Australia-wide www.scienceweek.net.au
73rd CSANZ Annual Scientific Meeting August 14–17, Brisbane www.csanzasm.com
Westwick-Farrow Media
A.B.N. 22 152 305 336 www.wfmedia.com.au
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