Lab+Life Scientist June/July 2024

BOOST YOUR MICROBIAL EXPOSURE WITH INDOOR GARDENING FASTER, MORE CONVENIENT PLASMA ISOLATION

GENE EDITING ELIMINATES HIV FROM CELLS

JUNE/JULY 2024 VOL.35 NO.2 PP100008671

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jun/jul 2024

Contents 6 FROM LAB TO LIFE: TRANSFORMATIVE APPLICATIONS OF MEDICAL PLASTICS

6

Demand for medical plastics is on the rise worldwide, due to their indispensable role in ensuring the safety and hygiene of healthcare settings.

12 CRISPR-CAS GENE EDITING ELIMINATES HIV IN LAB Scientists deployed CRISPRCas molecular scissors and two gRNAs against ‘conserved’ HIV sequences, and achieved cure of HIV-infected T cells.

12

17 INDOOR GARDENING BENEFICIALLY BOOSTS OUR MICROBIAL EXPOSURE Indoor gardening can increase the bacterial diversity of the skin and boost levels of anti-inflammatory molecules in the blood.

17

21 CLINICAL TRIAL TRANSFORMATION: RECENT CHANGES AND FUTURE PREDICTIONS Accelerated by the COVID-19 pandemic, we have seen a shift in clinical trials, with changes to the way they are conducted, regulated and perceived.

Proudly sponsored by

AMS Instrumentation & Calibration Solutions https://ams-ic.com.au

The sticky substance protects plants from diseases and pests by trapping them when they land on plant leaves, incapacitating them.

28 SMARTPHONE COMPASS USED TO MEASURE GLUCOSE Researchers have used an ordinary smartphone’s built-in magnetometer, or compass, to measure concentrations of glucose — a key marker for diabetes.

30 ONE-TWO PUNCH TREATMENT KNOCKS OUT ACUTE MYELOID LEUKAEMIA Researchers paired venetoclax, a current standard-of-care anticancer drug for acute myeloid leukaemia, with a STING agonist, an emerging class of immunotherapy drug.

32 COIN-SIZED DEVICE CAN ISOLATE PLASMA, REPLACING CENTRIFUGES Named ExoArc, the coin-sized chip can achieve high blood plasma purity by removing more than 99.9% of blood cells and platelets precisely and gently in just one step.

READ ONLINE! This issue is available to read and download at www.labonline.com.au/magazine

Cover image: iStock.com/CIPhotos

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25 STICKY PESTICIDE TO PROTECT CROPS FROM INSECTS

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editorial iStock.com/wildpixel

Don’t be a chicken!

A

few issues back, Lab+Life Scientist

featured an article on how gene editing can be used to create chickens that are partially resistant to infection by avian influenza. With bird flu now back in Australian headlines at the time of writing, thanks to outbreaks on several Victorian egg farms (as well as one human case in a returned traveller), it seems appropriate to check in on the latest research in this area.

In some good news, researchers at the University of Pennsylvania have developed an experimental mRNA vaccine against the highly pathogenic H5N1 strain of avian influenza. Unlike traditional influenza vaccines, which rely on replicating (and then inactivating) viruses in fertilised chicken eggs over a period of months, mRNA vaccines can be quickly and easily adapted to protect against different strains of influenza viruses and don’t require eggs for their development. This means scientists can start creating an mRNA vaccine within hours of sequencing a new viral strain with pandemic potential.

Having developed an mRNA vaccine targeting

subsequently infected with H5N1 cleared the virus

— and in this issue, we reveal how health-

more rapidly and displayed fewer symptoms than

promoting microbial exposure can be easily

unvaccinated controls, and also survived longer.

achieved through indoor gardening (page 17).

In some less good vaccine news, researchers

Other highlights include an oil-based pesticide

from the University of Cambridge and Fudan

that traps and incapacitates pest insects when

University have discovered that a single dose of

they land on leaves (page 25); glucose monitoring

the measles vaccine is up to 2.6 times more likely

using an ordinary smartphone (page 28); and

to be ineffective in children born by caesarean

gene editing that can eliminate all traces of HIV

section, compared to those born naturally. With

from infected cells (page 12) — which brings us

a C-section birth, children aren’t exposed to the

right back to the technology I mentioned at the

mother’s microbiome in the same way as with

start of this editorial!

a vaginal birth, and so miss out on the immune system boost that comes with it.

It’s a testament to all scientists that they are so willing not only to imagine new ways of doing

The researchers analysed data from previous

things, but to develop, test and perfect those new

studies of over 1500 children in China, which

ways. It just goes to shows that when it comes

included blood samples taken every few weeks

to science, you can’t hold back. You have to be

from birth to the age of 12. While many of

willing to put yourself out there — quite simply,

the children born by C-section did mount an

you can’t be a chicken!

immune response following a single vaccine dose, 12% had none, compared to 5% of children born by vaginal delivery. A second dose did induce robust immunity against measles in C-section children — but while everyone needs

Regards, Lauren Davis LLS@wfmedia.com.au

two doses of the vaccine in order for the body to mount a long-lasting immune response, a lot of

a subtype of the H5N1 virus that is circulating

children don’t end up having their second jab.

widely in birds and cattle, the researchers found

The researchers are now pushing for this second

that the vaccine elicited a strong antibody and T

dose in C-section babies in particular, since their

cell response in mice and ferrets, with the animals

first dose is more likely to fail.

maintaining high levels of antibodies even a year

Microbiota of course have a huge influence

after vaccination. Vaccinated animals who were

on our wellbeing, as we’re continually learning

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Lauren Davis

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Future Market Insights

Demand for medical plastics is on the rise worldwide, due to their indispensable role in ensuring the safety and hygiene of healthcare settings. And with a growing global population and increasing chronic diseases, the healthcare sector is expanding rapidly. This is projected to create a surging demand for medical equipment and devices.

M

edical plastics serve as a critical

component in the manufacturing of a wide range of products, including syringes, IV tubes, catheters, surgical instruments and diagnostic

From lab to life: transformative applications of medical plastics

devices. These are projected to contribute to the growth in demand.

Advancements in medical technology and innovations are set to propel demand for medical plastics. As medical research progresses, there is a constant need for improved and specialised medical devices that are lightweight and durable.

Demand for unique medical devices that are compatible with various sterilisation methods might also expand. Medical-grade plastics are set to offer an ideal solution. They can be moulded into complex shapes, incorporate unique features and maintain their functionality under demanding medical conditions.

Global focus on infection control and patient safety has further fuelled demand for medical plastics. Hospitals and healthcare facilities are continuously seeking ways to minimise the risk of infections and improve patient outcomes. Medical plastics possess inherent antimicrobial properties and can be easily cleaned and sterilised. They can help in reducing the potential for contamination and infection transmission, making them a preferred choice for medical equipment and disposable items.

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medical devices

Environmental considerations might also play a significant role in driving the demand for medical plastics. As sustainability becomes a priority for various sectors, including health care, there is a growing demand for ecofriendly medical solutions. Medical plastics have evolved to be more environmentally friendly as manufacturers are projected to use biodegradable and recyclable materials, reducing the environmental impact of medical waste.

Increasing focus on personalised medicine and minimally invasive procedures is likely to push demand for medical plastics worldwide.

As health care shifts toward patient-centric approaches, there is a growing need for medical devices that can be customised to individual patient requirements. Medical-grade plastics offer the versatility required to develop personalised implants, prosthetics and surgical tools. Additionally, a trend towards minimally invasive surgeries might augment demand for precision-engineered medical plastics.

Demand for innovative plastics that can deliver optimal performance while reducing trauma and scarring might increase. Versatility and adaptability of medical plastics would make them a crucial component in meeting the evolving demands of modern healthcare practices.

Which factors are pushing medical plastic demand worldwide?

Rapid shift towards minimally invasive procedures

A shift towards minimally invasive procedures has been a significant driver for growth in the medical plastics market. Minimally invasive procedures involve using small incisions or natural body openings to perform surgeries or medical interventions, instead of traditional open surgeries. This approach offers numerous advantages, including reduced trauma to patients, faster recovery times, shorter hospital stays and minimal scarring.

Medical plastics play a crucial role in enabling these procedures by providing the necessary tools and equipment. They are used to make a wide range of medical supplies and devices such as catheters, surgical instruments, implants, medication delivery systems and diagnostic iStock.com/ivan68

gadgets. These devices require materials that are sterile, biocompatible and lightweight.

Materials that have exceptional mechanical properties are also required. Medical plastics

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medical devices

can be utilised to create instruments and devices needed for minimally invasive procedures as they satisfy these requirements.

Rising demand for these procedures, driven by patient preferences and advancements in medical technology, has led to a corresponding increase in the demand for medical plastics.

Manufacturers and healthcare providers’ efforts to satisfy demands of the expanding minimally invasive surgery sector are likely to accelerate the medical plastics industry.

Self-administration of drugs and development of new drug delivery technologies iStock.com/Diomedes Cordero

As patients increasingly take an active role in their health care, there is a rising demand for user-friendly and convenient drug delivery systems. This trend has led to the development of innovative medical devices such as auto-injectors, inhalers and wearable injectors. These might allow patients to self-administer medications at home or on the go. These devices often rely

demand for healthcare solutions among the

for medical devices and equipment, including

elderly population.

those made from medical plastics. The ability of

on medical plastics due to their versatility,

Emphasis on infection control and patient

biocompatibility and ability to meet stringent

medical plastics to offer a balance between cost-

safety in healthcare settings has also led to an

regulatory requirements.

effectiveness and performance might make them

increased adoption of medical plastics. The

Medical plastics enable the production of

a key component in catering to diverse needs of

United States healthcare sector is keen on

components such as drug cartridges, syringes

patients. This burgeoning medical tourism sector

preventing hospital-acquired infections and

and inhaler parts, ensuring precise drug delivery

is set to contribute substantially to the astonishing

improving patient outcomes.

rise in medical plastic sales in China.

and patient safety. The integration of electronics,

Medical plastics possess inherent antimicrobial

sensors and connectivity features in drug delivery

properties and are easily sterilisable. This might

Competitive landscape

devices might further enhance their functionality

make them an ideal choice for producing medical

and patient monitoring capabilities.

Medical plastic manufacturers are investing

devices and equipment that adhere to the highest

in research and development to create

The expanding space of self-administered

hygiene standards.

drug delivery, coupled with advancements in

Why are medical plastic sales surging in China?

technology, would present lucrative opportunities

Medical plastic sales are experiencing an

for the medical plastics industry. It is projected to

astonishing surge in China due to the country’s

develop innovative solutions that cater to patient

rapidly expanding healthcare infrastructure. With

needs, improve treatment adherence and enhance

a growing middle-class population and increased

healthcare outcomes.

government investment in healthcare facilities, demand for medical devices has skyrocketed.

Country-wise insights

Medical plastics have become a preferred

Why is medical plastic demand increasing

choice for manufacturers and healthcare

rapidly in the United States?

providers in China. Ongoing modernisation and

In North America, the United States is expected to

development of hospitals and clinics across the

lead the medical plastics industry by 2033. North

country have further fuelled the need for medical-

America is estimated to hold around 34.1% of

grade plastics. These are set to help equip these

the global medical plastics market share in 2023.

facilities with cutting-edge medical technologies.

Medical plastic demand is expected to surge

Another significant factor pushing the

in the United States due to the increasing aging

remarkable growth in China is the country’s

population. As the baby boomer generation

thriving medical tourism sector. China has

continues to age, there is a higher prevalence of

emerged as a popular destination for medical

chronic diseases and a greater need for medical

tourism, attracting patients from around the

treatments and procedures.

world seeking high-quality medical treatments

Medical plastics might play a crucial role in

at competitive prices.

various medical devices, equipment and implants.

As medical tourists flock to China for

They are likely to help in meeting the growing

various procedures, there is a rising demand

innovative medical plastics that offer unique features, improved performance and enhanced functionality. Developing new materials and technologies allows them to offer cutting-edge solutions to healthcare providers, giving them a competitive advantage over traditional products.

They are increasingly focusing on offering customised and personalised solutions to meet specific needs of healthcare facilities and end users. By providing tailor-made products and services, they can better address diverse demands of the healthcare sector and strengthen their customer relationships.

To remain competitive, a few manufacturers are optimising their production processes to reduce costs while maintaining high-quality standards. Cost-effectiveness is crucial in a competitive market as it enables them to offer competitive pricing to customers without compromising on product quality.

These insights are based on the report ‘Medical Plastics Market’, written by Nikhil Kaitwade for Future Market Insights.

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movers&shakers

iStock.com/MangoStar_Studio

Nano carrier could enable oral insulin for diabetics A research team led by The University of Sydney (USyd) has used nanotechnology to develop a new type of oral insulin, which could offer a needle-free approach to managing diabetes. The researchers say their oral insulin, described in the journal Nature Nanotechnology, could be contained in a tablet or even embedded within a piece of sugar-free chocolate.

It is estimated 422 million people worldwide have diabetes and approximately 75 million of these inject themselves with insulin daily. But the development of a safe and effective form of oral insulin has been a challenge since insulin was discovered over a

Gentler form of IVF found to improve success rates A gentler form of IVF that can improve success rates is set to become more widely available, after the largest Australian study into the

century ago, as noted by USyd’s Dr Nicholas Hunt.

“A huge challenge that was facing oral insulin development is the low percentage of insulin that reaches the bloodstream when given orally or with injections of insulin,” Hoult said. “To address this, we developed a nano carrier that drastically increases the absorbance of our nano insulin in the gut when tested in human intestinal tissue.”

breakthrough technology delivered promising findings.

The ‘soft touch’ technique, known as Piezo-ICSI, works by gently penetrating an egg using high-speed vibration, rather than the standard cutting action used in conventional ICSI (Intracytoplasmic Sperm Injection). Hundreds of babies have been born as a result of Piezo-ICSI since Monash IVF introduced the Japanese-developed technique to Australia as part of a set of clinical trials in 2019.

In its latest study, Monash IVF recruited 108 patients from NSW, University of Sydney/Stefanie Zingsheim.

Victoria and Queensland to take part in the biggest study into PiezoICSI in Australia comparing Piezo-ICSI to standard ICSI. Half of the participants’ eggs were fertilised using standard ICSI technology and the other half through Piezo-ICSI. The type of injection used first was randomised to prevent bias.

The researchers found Piezo-ICSI resulted in a fertilisation rate of 71.6%, compared with 65.6% for standard ICSI. The results, published in the journal Fertility and Sterility, also showed half as many eggs suffered damage after fertilisation with the gentler method, while the quality of the embryos produced was higher.

“While pregnancy and birth rates are similar for both forms of ICSI, our research has found the soft touch technique can potentially reduce the number of rounds of IVF a woman needs to conceive,” said Dr Jinny Foo, Monash IVF Parramatta fertility specialist and researcher.

“We now have strong evidence from three separate trials that PiezoICSI can improve fertilisation success rates and hopefully help more couples and single women achieve their dreams of having a family.”

The technology is currently available at some of Monash IVF’s clinics in NSW, Queensland, Victoria and South Australia, with plans to introduce it into more clinics and states where it is currently not available. The treatment can only be accessed by eligible patients who may benefit from a gentler form of ICSI via the Therapeutical Goods Administration (TGA) special access scheme.

“For our fertility patients, particularly those who are older and do not have time on their side, it’s exciting to be able to offer this technology,” Foo said. “Even one extra embryo could make the world of difference to them — it could just be the one that makes their baby dreams come true.”

R&D version of the oral insulin capsule.

The team’s oral insulin utilises a nanoscale material that is 1/10,000th the width of a human hair. This material acts similarly to acid-resistant coating on tablets — which protects them from being destroyed by stomach acid — but instead surrounds individual insulin molecules and becomes a nano carrier, acting like a courier to ferry these molecules to the places they need to act.

Studies in mouse, rat and baboon animal models have shown that the greatest strength of the nanoscale material is that it can react to the body’s blood sugar levels. The coating dissolves and releases the insulin only when there is a high concentration of blood sugar, not in low blood sugar environments. There is also no toxicity or weight gain.

“Our oral insulin has the added benefit of greatly reducing the risk of hypoglycaemic episodes,” Hunt said, referring to a low blood sugar event where too much insulin has been injected. “For the first time, we have developed an oral insulin that overcomes this major hurdle.”

Human trials are expected to start in 2025, led by spinout company Endo Axiom.

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movers&shakers

New facility to deliver human challenge trials Australia’s first facility specifically

“By providing early and rapid efficacy data

commissioned to deliver human challenge

using small cohorts of participants, human

trials, Doherty Clinical Trials, has been

challenge trials can produce more reliable and

opened by Victorian Minister for Medical

reproducible results than studies in affected

Research Ben Carroll and Professor Sharon

patients where variables are less controlled,”

Lewin, Director of The Peter Doherty

McCarthy said.

Institute for Infection and Immunity. As

“With these type of studies, vital information

a not-for-profit registered charity and

about the efficacy of vaccines and potential

subsidiary of The University of Melbourne,

treatments can be received very quickly and at a

Doherty Clinical Trials has been established

significantly lower cost.

by the Doherty Institute to accelerate the

“As most drugs and vaccines fail along the

development of novel medicines and vaccines

clinical development pathway, it is advantageous

through bespoke early-phase clinical trials

to rapidly determine if development of a

solutions, including human challenge trials.

candidate vaccine or treatment should continue,

A human challenge trial allows researchers

or if the researchers should pivot to an alternative

to test the effectiveness of vaccines and

candidate with a higher chance of success.”

therapeutics for infectious diseases by

The establishment of Doherty Clinical

The Australian Institute for Infectious Disease is set to be the future home of Doherty Clinical Trials. Artist impression by Wardle.

“While human challenge trials have been used to develop new medicines and vaccines globally for decades, our purpose-built facility is the first of its kind in the Southern Hemisphere, and will build capabilities right here in Victoria enabling rapid research translation,” Lewin said.

“The COVID-19 pandemic highlighted the need to accelerate how new vaccines and

administering a well-characterised infectious

Trials was made possible by generous

agent to healthy volunteer participants, with

contributions from the Victorian Government

the aim of speeding up drug development.

and philanthropic funding via the Doherty

all to get lifesaving medicines more rapidly

Professor James McCarthy, Chief Medical

Institute. The 25-bed facility is currently

in future pandemics.”

Officer of Doherty Clinical Trials, said

located in the former Peter Mac building in

Upcoming human challenge trials will

human challenge trials are one of the most

East Melbourne, but in the future it will be

include influenza, Strep A, gonorrhoea and

efficient ways to evaluate the efficacy of

housed in the Australian Institute for Infectious

malaria, and will be conducted in partnership

novel vaccines and therapeutics.

Disease (AIID), set to be completed in 2027.

with Australian and global research teams.

treatments are developed. This will help us

Machine learning identifies 800,000+ antimicrobial peptides Nature has always been a good place to look for

— validating the team’s broad approach to

antibiotics, as bacteria have evolved numerous

exploring the world’s biological data.

antibacterial defences — often in the form of

To validate their findings, the researchers

short proteins (peptides) that can disrupt bacterial

synthesised 100 of the peptides and tested

cell membranes and other critical structures.

them against 11 disease-causing bacterial

Now, an international research team has used

strains, including antibiotic-resistant E.

machine learning to search for antibiotics in a

coli and Staphylococcus aureus. They found

vast dataset containing the recorded genomes of

that 79 disrupted the protective bacterial membranes and 63 completely eradicated

tens of thousands of bacteria and other primitive organisms — and identified over 800,000 potential antibiotic compounds in the process.

The study was co-led by researchers at the

For this new study, the researchers used a machine learning platform to sift through multiple public databases containing microbial

the growth of at least one of the pathogens tested, and often multiple strains.

“In some cases, these molecules were

University of Pennsylvania, including co-senior

genomic data. The analysis covered 87,920

effective against bacteria at very low doses,”

author Assistant Professor César de la Fuente.

genomes from specific microbes as well

de la Fuente said. Promising results were

In recent years, de la Fuente and colleagues

as 63,410 mixes of microbial genomes, or

also observed in preclinical mouse models,

have pioneered AI-powered searches for

metagenomes, from environmental samples

where treatment with some of the peptides

antimicrobials, identifying preclinical candidates

spanning diverse habitats around the planet.

produced results similar to the effects of

in the genomes of contemporary humans,

This extensive exploration succeeded in

polymyxin B — a commercially available

extinct Neanderthals and Denisovans, woolly

identifying 863,498 candidate antimicrobial

antibiotic which is used to treat meningitis,

mammoths and hundreds of other organisms.

peptides, more than 90% of which had

pneumonia, sepsis and UTIs.

“AI in antibiotic discovery is now a reality

never been described before. The identified

The team’s repository of putative antimicrobial

and has significantly accelerated our ability to

compounds originated from microbes living in

sequences, which they call AMPSphere, is freely

discover new candidate drugs,” de la Fuente said.

a wide variety of habitats — including human

available to access at https://ampsphere.big-

“What once took years can now be achieved in

saliva, pig guts, soil and plants, corals, and

data-biology.org/. Their research has also been

hours using computers.”

many other terrestrial and marine organisms

published in the journal Cell.

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movers&shakers

Gene editing could make quolls resistant to cane toad toxin Scientists from de-extinction company Colossal Biosciences and The University of Melbourne are on a quest to save the endangered northern quoll from the invasive cane toad, using proprietary tools to introduce genetic resistance against the cane toad toxin into marsupial cells.

Ever since the introduction of invasive cane toads to Queensland in the 1930s, northern quolls have seen their populations plummet by 75%.

This is because the toads — which have since spread into coastal NSW, the Northern Territory’s Top End and the Kimberley region of Western Australia — are an attractive food source for the northern quoll, which is especially vulnerable to the toad’s neurotoxins.

“We need northern quolls to have a balanced ecosystem in mainland Australia,” said Professor Andrew Pask, who leads Melbourne’s Thylacine Integrated Genetic Restoration Research (TIGRR) Lab. “By using Colossal’s technology, we’re giving our conservation partners a fighting chance of succeeding in restoring that balance.”

Observations of other genetically resistant species by Dr Stephen Frankenberg, a member of Pask’s lab, led the researchers to hypothesise

that northern quolls could become genetically resistant with a very small genetic intervention.

After building resources from northern quoll tissue samples and introducing different genetic edits to the cells of a dunnart, which is closely related to the northern quoll and serves as a useful model species, the team successfully engineered resistance in dunnart cells (which Colossal has used for its research into thylacine de-extinction) by introducing genetic features found in other natural predators of toads. The edited cells are 10-fold more toxin-resistant in the context of cell culture, with the team predicting this resistance will extend to the whole animal.

As a next step in introducing toxin resistance to the northern quoll, the team has established eight northern quoll cell lines from pouch young.

They are now working to reprogram those quoll fibroblasts into induced pluripotent stem cells (iPSCs); once the iPSCs are generated, the scientists can correct the toxin susceptibility at the cellular level. The offspring of these quolls, and their offspring again, should inherit this resistance against cane toad toxins, which theoretically means that no further intervention will be necessary to protect the species.

The team not only hopes that the quolls will become toxin-resistant, but that they will become a primary predator of cane toads and so help to slow the toads’ growing population. The researchers also hope to save other threatened species who consume and can die from cane toads.

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gene editing iStock.com/Artem_Egorov

CRISPR-Cas gene editing eliminates HIV in lab

New research presented at this year’s European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2024), held in Barcelona from 27–30 April, shows how the latest CRISPR-Cas gene editing technology can be used to eliminate all traces of HIV from infected cells in the laboratory.

The studies, conducted at Amsterdam University Medical Center (Amsterdam UMC), present a significant breakthrough in the search for a cure for HIV.

C

The scientists deployed CRISPR-Cas

successful, enhancing its delivery to HIV-infected

molecular scissors and two gRNAs against

cells. Moreover, they were able to target ‘hidden’

RISPR-Cas gene editing technology

‘conserved’ HIV sequences, meaning they focused

HIV reservoir cells by focusing on specific

is a groundbreaking technique that allows for

on parts of the virus genome that stay the same

proteins found on the surfaces of these cells

precise alterations to the genomes of living

across all known HIV strains, and achieved cure

(CD4+ and CD32a+).

organisms, enabling scientists to accurately target

of HIV-infected T cells. By focusing on these

“We have developed an efficient combinatorial

and modify specific segments of an organism’s

conserved sections, the approach aims to provide

CRISPR-attack on the HIV virus in various

DNA. Functioning like molecular ‘scissors’ with

a broad-spectrum therapy capable of combating

cells and the locations where it can be hidden in

the guidance of guide RNA (gRNA), CRISPR-

multiple HIV variants effectively.

reservoirs, and demonstrated that therapeutics can

Cas can cut the DNA at designated spots. This

However, the team found that the size of the

be specifically delivered to the cells of interest,” the

action facilitates either the deletion of unwanted

vehicle or ‘vector’ used to transport the cassette

scientists stated. They said their findings represent

genes or the introduction of new genetic material

encoding the therapeutic CRISPR-Cas reagents

a pivotal advancement towards designing a cure

into an organism’s cells, paving the way for

into the cells presented logistical challenges,

strategy for HIV, while acknowledging that their

advanced therapies.

as it was too large. Thus, they trialled various

work at this stage is only a proof of concept.

One of the significant challenges in HIV

techniques to reduce the size of the cassette — and

“Our next steps involve optimising the

treatment is the virus’s ability to integrate its

therefore the vector system itself. In simpler terms,

delivery route to target the majority of the HIV

genome into the host’s DNA, making it extremely

they’re attempting to pack oversized luggage

reservoir cells,” the researchers said. “We will

difficult to eliminate. Numerous potent antiviral

into a compact car for a journey to the infected

combine the CRISPR therapeutics and receptor-

drugs are currently in use for treating HIV

cell, leading them to find ways to downsize the

targeting reagents and move to preclinical

infection — but despite their efficacy, lifelong

‘luggage’ (cassette) for easier transport. Another

models to study in detail the efficacy and safety

antiviral therapy is essential, as HIV can rebound

issue they wanted to overcome was reaching the

aspects of a combined cure strategy. This will be

from established reservoirs when treatment is

HIV reservoir cells that ‘rebound’ when HIV

instrumental to achieving preferential CRISPR-

halted. CRISPR-Cas genome editing thus provides

antiretroviral treatment is stopped.

Cas delivery to the reservoir cells and avoiding

The researchers further evaluated various

delivery into non-reservoir cells. This strategy

“Our aim is to develop a robust and safe

CRISPR-Cas systems from different bacteria

is to make this system as safe as possible for

combinatorial CRISPR-Cas regimen, striving for

to determine their effectiveness and safety in

future clinical applications.

an inclusive ‘HIV cure for all’ that can inactivate

treating CD4+ T cells infected with HIV. They

“We hope to achieve the right balance between

diverse HIV strains across various cellular

shared results from two systems, saCas9 and

efficacy and safety of this cure strategy. Only

contexts,” the Amsterdam team said. With HIV

cjCas. SaCas9 showed outstanding antiviral

then can we consider clinical trials of ‘cure’ in

able to infect different types of cells and tissues in

performance, managing to completely inactivate

humans to disable the HIV reservoir. While these

the body, each with its own unique environment

HIV with a single guide RNA (gRNA) and

preliminary findings are very encouraging, it is

and characteristics, the researchers are searching

excise (cut out) the viral DNA with two gRNAs.

premature to declare that there is a functional

for a way to target HIV in all of these situations.

The strategy of minimising the vector size was

HIV cure on the horizon.”

a new means to target HIV DNA.

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what’s new

Structural characterisation of RNA and thermal ramping RedShiftBio’s Aurora TX, powered by microfluidic modulation spectroscopy (MMS), fully characterises the structure and stability of RNA, proteins, peptides and other biomolecules at the touch of a button, including thermal ramping to unlock a range of insights.

The product is designed to set a new standard in biomolecular analysis, with background-subtracted measurements of a wide range of biomolecules in the formulation of interest and in concentrations ranging from 0.1 to >200 mg/mL. This level of accuracy and versatility, coupled with an easy, automated workflow, utilisation of 96-well plates and fully integrated analytical software, addresses the limitations of existing technologies such as CD and FTIR. Aurora TX empowers researchers to delve deep into the characterisation of nucleic acids, proteins and other biomolecules without the need for spectroscopy expertise. With the ability to compare higher-order structures, stability profiles and similarity profiles, it facilitates informed decision-making across various stages of biopharmaceutical drug development, from discovery to quality control.

The most significant development of Aurora TX is its growing application in RNA analysis. Researchers can use the device to detect structural changes to RNA due to sequence modifications, formulation changes and thermal stress. Even structural differences in the payload upon LNP encapsulation and RNA-to-LNP ratio are now measurable, all with walkaway automation.

The integration of thermal ramping in Aurora TX adds an extra dimension to biomolecular analysis by enabling researchers to induce high-resolution temperature stress, which should facilitate the detection of structural changes with precision and repeatability.

This feature streamlines the analysis process, saving time and resources for researchers engaged in drug discovery and development.

ATA Scientific Pty Ltd www.atascientific.com.au

Digital pressure gauge NOSHOK has announced the rugged PGE20 Series general-purpose digital pressure gauge, which replaces its legacy 1000 Series digital gauge and provides additional features and benefits. The optional enhanced features that were available on the 1000 Series digital gauge are now standard on the PGE20 Series, including the configuration software.

Gauge, compound, absolute and vacuum ranges are available from 35 kPa to 100 mPa. The gauge features a 4½-digit display with a 0–100% bar graph and 316L stainless steel wetted parts.

The menu functions include a min/max alarm (visual), auto power-off, tare offset, battery status display and backlighting. An optional integrated data logger is also available and can be field activated.

The range of applications for the gauge are numerous and include hydraulics and pneumatics, leak detection, water management, hydrostatic pressure testing, burst testing and setting pressure switch set points.

AMS Instrumentation & Calibration Pty Ltd www.ams-ic.com.au

14 This issue is sponsored by | AMS Instrumentation & Calibration Solutions | www.ams-ic.com.au

what’s new

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research. The LI-COR Odyssey M Western blot imager has been designed to uphold high standards of imaging throughout every stage of research, from data acquisition through to analysis and publication.

The Odyssey M goes beyond traditional imaging systems to offer considerable versatility as a Western blot imager, plate reader, slide scanner, luminescence imager and much more. It accommodates membrane, plate, gel and slide-based assays, consolidating multiple imaging tasks into a single system.

With 18 imaging channels, including near-infrared and visible fluorescence, bio- and chemiluminescence, and RGB true colour, it facilitates a wide range of research possibilities from virus and cancer research to microbiome studies.

The instrument features a true 6-log dynamic range, empowering researchers to achieve good productivity in the lab without compromising data integrity. In a single data acquisition, capturing a full depth of data in less than 3 min provides high efficiency.

Utilising a line scanning system enhanced with sCMOS sensor technology, the Odyssey M delivers high resolution and sensitivity. This technology means that researchers can capture intricate details with clarity, whether examining tissue sections or probing molecular interactions.

With the Odyssey M, researchers can obtain highquality images for analysis and interpretation, reinforcing the validity of their research findings.

Millennium Science Pty Ltd

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This issue is sponsored by | AMS Instrumentation & Calibration Solutions | www.ams-ic.com.au 15

what’s new

Spike-in normalisation Variations across data may obscure true differences between samples in ATAC-Seq, CUT&RUN or CUT&Tag assays. Active Motif has now developed, validated and published spike-in reagents for ChIP-Seq, and has introduced this valuable tool

Benchtop meter for pH and ORP

for ATAC-Seq, CUT&RUN, CUT&Tag and CUT&Tag R-loop assays. Now variation between datasets

Designed with a large LCD display and six instructional menu buttons, the

can be normalised to enable sample comparison

AB23PH, distributed by Pacific Labs, is a simple and straightforward pH

and reveal true biological differences.

meter. Auto buffer recognition and a three-point calibration capability help to

With spike-in normalisation control, scientists

provide an appropriate calibration result, while a standalone holder increases

can compare datasets between samples in ATAC-

flexibility for routine experiments and helps to save space in the lab. A 99-

Seq, CUT&RUN or CUT&Tag assays. Users simply

item memory for pH measurements enables efficient data documentation.

need to add spike-in nuclei to their samples and

The pH meter model AB23PH-F has a measurement range of 0–100°C,

perform the assay together in one reaction — this

0.00–14.00 pH and -1999–1999 mV, with a measurement resolution of

will enable them to obtain the normalisation factor

0.1°C/0.01 pH/1 mV. It features an LCD with backlight; a buffer and beaker

and reveal the true differences between samples.

are not included.

United Bioresearch Products Pty Ltd

Pacific Laboratory Products

www.unitedbioresearch.com.au

www.pacificlab.com.au

Sterile silicone adhesives When looking for a low-toxicity adhesive with some elasticity and good moisture resistance, a silicone adhesive is particularly suitable. These work well with living tissue, as they are non-toxic, fast curing and able to adhere to organic and inorganic surfaces.

Coherent Scientific has now introduced the sterile KWIK-SIL and KWIK-CAST silicone adhesives from World Precision Instruments (WPI). The sterile versions of these adhesives are suitable for laboratories that cannot sterilise KWIKCAST/KWIK-SIL in their facilities.

The properties of the biocompatible surgical adhesives make them useful for neuroscience applications, peripheral nerve studies and similar biomedical applications. The silicone elastomers also eliminate the mess and time involved in pre-mixing other commonly used formulations.

Coherent Scientific Pty Ltd www.coherent.com.au

16 This issue is sponsored by | AMS Instrumentation & Calibration Solutions | www.ams-ic.com.au

microbiota

Mika Saarenpää

Indoor gardening iStock.com/s-cphoto

beneficially boosts our microbial exposure

Researchers at the University of Helsinki, Natural Resources Institute Finland and Tampere University have demonstrated that indoor gardening can increase the bacterial diversity of the skin and boost levels of anti-inflammatory molecules in the blood. The results of their research have been published in the journal Environment International.

his research subjects to commit to urban gardening

observed in just one month, but as the research

for one month. The experimental group used a

subjects enjoyed the gardening, many of them

growing medium with high microbial diversity

said they would continue the activity and switch

emulating forest soil, while the control group used

to outdoor gardening in the summer.

a microbially poor peat-based medium.

A

“We don’t yet know how long the changes

“One month of urban indoor gardening

observed in the skin microbiota and anti-

boosted the diversity of bacteria on the skin of the

inflammatory cytokines persist, but if gardening

[experimental] subjects and was associated with

turns into a hobby, it can be assumed that the

higher levels of anti-inflammatory cytokines in the

regulation of the immune system becomes

blood,” Saarenpää said. In contrast, no changes in

increasingly continuous,” Saarenpää said.

the blood or the skin microbiota were seen in the

Saarenpää stated that microbe-mediated

control group. This suggests that peat — the most

immunoregulation can reduce the risk of immune-

widely used growing medium in the world and

mediated diseases or even their symptoms

a large contributor to greenhouse gas emissions

— so if health-promoting microbial exposure

— does not bring any health benefits similar to a

could be increased at the population level, the

medium mimicking diverse forest soil.

healthcare costs associated with these diseases

“We know that urbanisation leads to

could be reduced and quality of life increased.

reduction of microbial exposure, changes in

He said it is particularly important to invest in

the human microbiota and an increase in the

children’s exposure to nature and microbes —

s part of his doctoral thesis, Helsinki’s

risk of immune-mediated diseases,” Saarenpää

as the development of the immune system is at

Mika Saarenpää investigated how microbial

said. “This is the first time we can demonstrate

its most active in childhood — and so suggested

exposure that promotes the health of urban

that meaningful and natural human activity can

introducing planter boxes filled with microbially

residents, particularly enhancing their immune

increase the diversity of the microbiota of healthy

rich soil in kindergartens, schools and hospitals,

regulation, could be increased easily through

adults and, at the same time, contribute to the

especially in densely built urban areas.

meaningful activities integrated into everyday

regulation of the immune system.”

“My research emphasises the dependence of

life. According to Saarenpää, urbanisation has led

Saarenpää’s study shows that microbial

our health on the diversity of nature and that of soil

to a considerable increase in immune-mediated

exposure can be increased easily and safely in

in particular,” he said. “We are one species among

diseases such as allergies, asthma and autoimmune

the home, with only a small amount of space and

others, and our health depends on the range of

diseases, as we live too ‘cleanly’ in cities.

financial investment required. The gardening took

other species. Ideally, urban areas would also have

Knowing from previous studies that contact

place in regular flower boxes, while the plants

such a diverse natural environment that microbial

with nature-derived, microbially rich material can

cultivated, such as peas, beans, mustards and

exposure beneficial to health would not have to

alter the human microbiota, Saarenpää instructed

salads, came from the shop shelf. Changes were

be sought from specifically designed products.”

This issue is sponsored by | AMS Instrumentation & Calibration Solutions | www.ams-ic.com.au 17

what’s new

High-density microelectrode array (HD-MEA) system MaxOne, from MaxWell Biosystems, is a CMOS-based HD-MEA; an electrical imaging system for neuroscience, drug discovery and cell assessment applications. It captures high-quality signals at subcellular resolution from acute tissue experiments (eg, brain slices, retina) and long-term culture experiments. Simultaneous recordings can be performed by running up to four recording units in one system.

A powerful electrophysiology platform for recording and stimulating electrogenic cells in vitro, MaxOne is a high-density microelectrode array system in a single-well format that allows for easy and vibrationfree insertion of the MEA device. It can operate inside cell-culture incubators and accessories are available for perfusion compatibility. Microscopy of samples on the HD-MEA surface can be performed using upright objectives.

The system comes in two options. The MaxOne Full offers 1020 recording channels and 32 stimulation channels, while the MaxOne Basic offers 256 recording channels and no stimulation channels. The MaxOne Full also offers unlimited electrode configurations, whole sample electrical imaging, axon tracking and smart population recording. Both units offer MATLAB and Python data analysis tools.

SciTech Pty Ltd www.scitech.com.au

Particle sizing with integrated AI Malvern Panalytical’s Mastersizer 3000+ range is designed to offer an advancement in particle size analysis, combining decades of expertise with state-of-the-art technology.

Seamlessly integrating artificial intelligence (AI) and data science-driven software solutions, the cutting-edge instrument offers a helping hand to users at all proficiency levels. Software solutions for method development support, data quality feedback, instrument monitoring and troubleshooting advice help streamline operation and simplify the route to achieve high-quality particle size data, positively impacting product research, development and manufacturing.

Size Sure is a feature that delves deeper into sample analysis, which investigates both steady and transient states to enable the reproducibility of size distribution measurements while shedding light on potential contaminants and other critical factors.

SOP Architect, driven by machine learning algorithms, constructs optimal analytical methods for each sample, complemented by guided workflows.

Embedded data quality guidance promptly alerts users to any issues, facilitating swift corrective action.

Smart Manager connectivity provides proactive advice on maintenance

Digital PCR system Stilla’s Nio is a versatile, all-in-one, fit-for-throughput, digital PCR instrument with high levels of user-friendliness. With features including a giant touchscreen interface and Crystal Digital PCR technology, the next-generation digital PCR system provides high partition density and allows persistent access to every individual PCR micropartition for full documentation, advanced assay QC and assay rescanning capabilities.

Multiplexing is the next frontier for digital PCR — and with seven channels, Nio has this covered.

Besides full TaqMan support, a seven-colour probe chemistry from Stilla called Flex Probe supports 21-plex assays.

The system is suitable for busy labs with many users, as its continuous loading capability means a new assay plate can be added into the instrument at any time and it can process up to 768 samples in an 8 h workday. Even though the product is fully automated once a plate is loaded, automating upstream PCR plate set-up can be done with a variety of robotic liquid handling

requirements, pre-empting part failures and replacements for uninterrupted

workstation options.

optimal instrument performance and minimal analytical downtime.

Bio-Strategy - Part of DKSH Group

The Mastersizer 3000+ Lab is an entry-level system offering robust size

www.bio-strategy.com

measurements from 0.1 to 1000 µm, empowered by the Mastersizer Xplorer software, while the Mastersizer 3000+ Pro is a mid-tier system providing robust size measurements with advanced software experience and automated dispersion options. The Mastersizer 3000+ Ultra offers the widest size range (0.01–3500 µm) and automation support, driven by the digitally enhanced Mastersizer Xplorer with AI-powered workflow applications, including the Size Sure measurement mode.

ATA Scientific Pty Ltd www.atascientific.com.au

18 This issue is sponsored by | AMS Instrumentation & Calibration Solutions | www.ams-ic.com.au

SPONSORED CONTENT

KE Select partners with Southern RNA to support biomanufacturing workforce planning iStock.com/PeopleImages

KE Select, a leading scientific and medical recruitment agency, has entered into partnership with Southern RNA, a ground-breaking biomanufacturing organisation, to source and select exceptional technical talent to further their research into mRNA technology and nucleic acid manufacturing.

“We’re thrilled to be working with Southern RNA

of contacts, spanning Australia, New Zealand and

and look forward to helping them find and recruit

the rest of the world, to source top-tier talent to fill

scientists who will work synergistically with their

positions at every level within Southern RNA.

already excellent team to deliver innovative and

“For more than 12 years, we’ve helped

effective solutions for their customers,” said

companies in the biomanufacturing sector find

Kerry McMahon, CEO of KE Select.

the right people. So we know just how crucial it

People are key to capitalise on the biomanufacturing boom

is to employ the right candidates to fill positions

Over the past decade, Australia has become

Getting the right mix of experience and fresh ideas is paramount

at all levels of the organisation,” Kerry adds.

a global contender in the biomanufacturing landscape,

contributing

to

lifesaving

therapeutics, impacting global health. Our extraordinary

research

and

clinical

trial

capabilities, coupled with streamlined and globally recognised regulatory pathways that expedite research from bench to bedside, have attracted unprecedented levels of funding from Government and the private sector.

For companies such as Southern RNA to capitalise on this boom in the industry, it’s vital that they hire the right people — scientists who will elevate their research, products and services to even greater heights, satisfying their customers and attracting greater investment.

“Infrastructure and funding are important,

“Positioned as it is in the heart of Australia’s research sector, it is crucial for Southern RNA to attract and employ the right mix of scientists and technical staff, including

Southern RNA set to benefit from partnering with a science recruitment specialist “Our partnership with Southern RNA, like all our partnerships, goes beyond merely filling vacancies,” says Kerry. “We form long-term relationships with our clients as this gives us an in-depth understanding of how the organisation functions and greater insight into the company ethos. This allows us to screen candidates for expertise and personality traits that will work best within the team. We also keep an eye out for subtle shifts in the industry and the impact these will have on our client’s needs, so we can work proactively with the client to ensure seamless transitions as people leave and join the company.”

This partnership shows Southern RNA’s firm commitment to hiring the best possible candidates who will further their already impressive molecular engineering, microbial cell bank production, plasmid DNA production (linear and supercoiled), and mRNA production services.

both seasoned professionals and university graduates,” Kerry explains.

“University and TAFE graduates bring fresh ideas and knowledge of the latest innovations, while more experienced scientists draw on wisdom and insights gained over years at the coalface. These individuals are invaluable as they provide the training and leadership necessary for younger members of staff to thrive.”

of course,” says Kerry, “but finding the right

The science and medical recruitment agents

people is really the key to ensure that your

at KE Select will assist Southern RNA with

company is ready to deliver the high standards

identifying the skill sets and levels of experience

of innovation, productivity and quality that

required for each role. They will then cast the

today’s biomanufacturing industry demands.”

net far and wide to yield a selection of high-

The team at KE Select is deeply engaged in

calibre candidates from which Southern RNA

the Australian biomanufacturing space and,

will build a strong team to drive growth in this

therefore, able to draw on an extensive network

lucrative industry.

Founded in 2012 by Director Kerry McMahon, BSc Biomedical Science, KE Select is a leading Australian-based scientific and medical technology recruitment agency. Partnering with a wide range of organisations within the life science, medical, clinical, pharmaceutical, hospital and healthcare space, the agency sources and selects top-tier scientific and technical talent throughout Australia, New Zealand and the rest of the world.

KE Select www.keselect.com

This issue is sponsored by | AMS Instrumentation & Calibration Solutions | www.ams-ic.com.au 19

what’s happening

Cyto-Mine transforms cell line development Scientists at FUJIFILM Diosynth Biotechnologies have transformed their cell line development processes through the incorporation of Cyto-Mine, a next-generation single-cell analysis system developed

by Sphere Fluidics. The new processes are streamlined, compared with previous workflows, and productivity has been enhanced.

Projects are now able to swiftly transition from the initial transfection phase through to development of highly productive cell lines within approximately 10 weeks.

Cell line development: critical objectives and challenges Specialist contract development and manufacturing organisations (CDMOs) offer technical expertise and capacity in cell line and process development to optimise production of biological medicines for biotherapeutic manufacturers. In this commercially competitive field, CDMOs are under increasing pressure to deliver robust and productive stable cell lines within shortened timeframes, to drive faster transfer of therapeutic molecules into clinical development. This must be achieved while maintaining excellence concerning biological product quality.

and Drug Administration (FDA), require evidence of monoclonality regarding cell lines used in the production of biological medicines.

Traditional approaches do not allow visualisation of individual cells upon initial seeding, making demonstration of monoclonality difficult or impossible in certain cases.

Cyto-Mine in practice: improving efficiency and ensuring quality Cyto-Mine enables individual cells to be encapsulated within picolitresized aqueous droplets in a biocompatible carrier oil (picodroplets).

FUJIFILM Diosynth Biotechnologies has harnessed this technology to develop a single-step cloning process, which removes bottlenecks in the cell development process and improves both accuracy and efficiency.

Each picodroplet provides a controlled, defined and adjustable environment that maintains cell viability. Single cells may be screened with speed and precision while secreted proteins are trapped within the picodroplets, making them easily accessible for characterisation.

Figure 1: Cyto-Mine workflow — integration of productivity assay screening, sorting, isolation and verification using a fully automated picodroplet microfluidic process.

Technologies that provide better predictive screening capabilities and higher throughputs than those traditionally used in cell line development laboratories have been sought to meet the growing urgency and demand for unique biotherapeutic molecules.

Conventional manual screening techniques, such as colony picking and limiting dilution cloning, are time-consuming, laborious and restricted concerning the number of cells that can be processed or analysed within a given period. Industry regulators, such as the Food

Multiple procedures and assays within the cell line development pathway are miniaturised and integrated within Cyto-Mine (Figure 1), allowing tasks that would previously have taken weeks to complete to be undertaken within one day. Approximately 200,000 individual cells can be screened in a matter of hours using this approach, compared with around 10,000 cells with manual analysis techniques.

Quality and quantity of molecular product are enhanced as screening is now conducted at an early stage so that only cells expressing the protein of interest, and the best-performing cells within this pool, are taken forward in the development process.

Workflows have been significantly shortened, from around 25 weeks to approximately 10 weeks (Figure 2). Importantly, single cells may be visualised using Cyto-Mine and monoclonality data can be provided to support regulatory submissions.

Overall efficiency and productivity in the cell line and process development team at FUJIFILM Diosynth Biotechnologies has been enhanced through the application of Cyto-Mine. Scientists spend less time conducting laborious manual procedures and are able to complete a greater number of projects within a given timeframe.

This allows them to apply their specialist skills and expertise to other important aspects of their work. Motivated by the possibilities of Cyto-Mine, the scientists are now exploring further applications using this technology platform.

Figure 2: Example timeline highlighting the streamlining of workflows using Cyto-Mine.

Capella Science www.capellascience.com.au

20 This issue is sponsored by | AMS Instrumentation & Calibration Solutions | www.ams-ic.com.au

clinical trials

Envirotainer

Clinical trial transformation Recent changes and future predictions iStock.com/metamorworks

Clinical trials play a pivotal role in advancing medical research and improving patient care, and are an essential part of new drug development. In recent years, clinical trials have undergone significant changes driven by technological advancements, regulatory shifts and a growing emphasis on patient-centricity.

A

ccelerated by the COVID-19

pandemic, we have seen a shift in clinical trials, with changes to the way they are conducted, regulated and perceived. In this article, we will explore the recent transformations in the world of clinical trials and offer insights into their potential future direction.

Recent changes in clinical trials One of the most prominent recent developments in clinical trials is the increasing use of realworld evidence (RWE). RWE uses data from a variety of sources, including electronic health records, insurance claims and wearable devices.

This allows researchers to gather data beyond

also known as virtual, at-home or site-less trials.

focuses on quality, and establishes proportionate

With the implementation of telemedicine and

and risk-based approaches for conducting

home-based monitoring, patients can take part in

clinical trials, while minimizing unnecessary

trials from the comfort of their homes, eliminating

complexities”. New recommendations include

the need to travel to specific sites. This approach

encouraging the use of innovative digital health

has shown increased patient participation and

technologies (DHTs), such as wearable sensors,

increased study effectiveness, and will ultimately

to increase the efficiency of data collection.

help to get drugs to market faster.

European Union: The EU has implemented

There has also been a growing emphasis on

a new Clinical Trials Regulation (CTR) to

patient-centricity in more recent clinical trials.

create a more unified and efficient framework

Regulatory agencies and sponsors are actively

for clinical trials across member states.

involving patients in the trial design process to

The CTR, fully implemented in early 2023,

ensure that the research is aligned with patients’

simplifies the approval process, harmonises

needs and preferences. This approach not only

trial designs and establishes a single portal for

enhances the relevance of the trials but also

trial submissions. These changes are expected

increases patient recruitment and retention rates.

to reduce administrative burdens and enhance

Several countries have undergone significant changes in their clinical trial regulations to adapt to the changing landscape:

the competitiveness of EU clinical research.

India: In 2019, the Ministry of Health and Family Welfare (MoHFW), Government of India

traditional clinical trial settings, providing

United States: In June 2023, the FDA

released updated New Drugs and Clinical Trials

a more comprehensive view of a treatment’s

announced the availability of a new draft

Rules, designed to help streamline regulations and

effectiveness and safety.

guidance, ‘E6(R3) Good clinical Practice (GCP)’.

guide clinical trial conduct in India. These updated

The COVID-19 pandemic accelerated the

The latest draft guidance includes updated

rules include new time limits for responses to

adoption of remote and decentralised clinical trials,

recommendations and “encourages innovation,

submissions for application for clinical trials.

This issue is sponsored by | AMS Instrumentation & Calibration Solutions | www.ams-ic.com.au 21

clinical trials

United Kingdom: Announced in October 2023, a series of new measures will be

trial designs, better patient selection and early

clinical research, will help to guide pharmaceutical

identification of safety concerns.

companies’ approach towards clinical trials.

introduced by the Medicines and Healthcare

Expansion of decentralised trials: The

The world of clinical trials has evolved

products Regulatory Agency (MHRA) to

trend of decentralised and remote trials will

significantly in recent years, with an emphasis

streamline clinical trial approvals. Under the

expand, making participation more convenient

on real-world evidence, patient-centricity, and

new framework, clinical trials application

for patients. Regulatory agencies will further

streamlined regulatory processes. These changes

processes in the UK will be more streamlined

support this shift by providing clear guidelines

have made clinical trials more efficient, patient-

and flexible without compromising on safety,

for virtual trials.

friendly and globally connected. The future holds

helping to make it faster and easier to gain

Enhanced regulatory flexibility: Regulatory

even more promise with advanced data analytics,

approval and to run clinical trials in the UK. The

agencies are expected to keep a more flexible

decentralised trials, global harmonisation and the

changes will also result in a framework that is

approach, enabling faster responses to emerging

rise of personalised medicine. As we continue to

responsive to diverse types of trials and designs,

health crises. Collaborative relationships between

navigate the ever-changing landscape of clinical

and supportive of new ways of conducting trials

the pharmaceutical industry and regulatory

such as decentralised trials.

bodies are likely to continue evolving to

trials, the ultimate beneficiaries will be patients

streamline the approval process.

Personalised medicine: Advancements in

Predictions for the future of clinical trials The future of clinical trials will continue to be

genomics and biomarker discovery will drive the

shaped by ongoing developments and emerging

development of targeted therapies. Clinical trials

trends. Here are some predictions on what we

will need to adapt to consider individual genetic

think will shape clinical trials in the coming years:

profiles and treatment responses, paving the way

Advanced data analytics: The integration

for targeted therapies.

of artificial intelligence and machine learning

Real-world data will be critical in decision-

will revolutionise data analysis in clinical

making: Emerging technologies and new devices

trials. Predictive modelling, data mining and

will enable companies to gather large amounts of

real-time monitoring will enable more efficient

real-world evidence. This data, along with data from

who receive safer and more effective treatments because of these innovations.

For more information, please visit www.envirotainer.com.

1. https://www.fda.gov/regulatory-information/search-fdaguidance-documents/e6r3-good-clinical-practice-gcp 2. https://www.ema.europa.eu/en/human-regulatoryoverview/research-and-development/clinical-trialshuman-medicines/clinical-trials-regulation 3. https://ijper.org/sites/default/files/ IndJPhaEdRes_53_4s_451_0.pdf 4. https://www.europeanpharmaceuticalreview.com/ news/187569/mhra-regulation-overhaul-new-schemefor-lowest-risk-uk-clinical-trials/

Gel imaging system and chemiluminescence instrument The SCG-W5000 dual imaging system, available from Pacific Laboratory Products, is a device that uses chemiluminescence technology for imaging and also combines regular UV for general gel viewing. Equipped with a highsensitivity cooled camera with a resolution of 20 million pixels, it enables fast, high-throughput detection and imaging of samples without the need for additional light sources. It has extensive applications in life sciences, pharmaceuticals, environmental protection and more.

The chemiluminescence imaging system has a clever AI algorithm, capable of quickly calculating the optimal exposure time. With deep

Black wall cell culture dishes

cooling, high sensitivity and a high-resolution

WPI’s FluoroDish black wall cell culture dishes

camera, it is capable of detecting weak signals,

are designed to reduce reflections by provid-

reducing image noise.

ing a barrier for the ambient light, providing

The unit includes standard analysis software,

clear fluorescent images. Their ability to

capable of automatically identifying and analysing

reduce ambient light makes them useful for

lanes; a large 10.4″ touchscreen computer, also

fluorescence live cell imaging.

compatible with external computers; a one-button

As with other FluoroDish products from WPI,

control switch; and simple and intuitive operation.

the optical-quality glass bottom is as thin as

It has a resolution of 5440 x 3648, a pixel size

the coverslip to offer the least amount of distor-

of 2.4 x 2.4 µm and cooling to -40°C, making it

tions and good UV transmission. Each pack is

a useful laboratory addition.

individually packaged and gamma sterilised.

Pacific Laboratory Products

Coherent Scientific Pty Ltd

www.pacificlab.com.au

www.coherent.com.au

22 This issue is sponsored by | AMS Instrumentation & Calibration Solutions | www.ams-ic.com.au

what’s new

Total chlorine analyser The TC80 Total Chlorine Analyzer from Electro-Chemical Devices (ECD) is designed to eliminate consumables, simplify installation and reduce maintenance with a selfcleaning design, lowering the total cost of ownership.

Panel mounted and ready-to-go out of the box, the easy-to-use device monitors total chlorine in drinking water, industrial cooling and rinse water, wastewater or other freshwater samples containing chlorine in the range of 0–20 ppm. Its Total Chlorine Sensor (TCS) is a three-electrode amperometric sensor that measures all chlorine species in the water, combined chlorine and free chlorine in a range of 0.05–20 ppm Cl2 (high range) or 0.005–2 ppm (low range).

The analyser’s plug-and-play design incorporates a flow control device, a pH sensor and the T80 transmitter mounted on a PVC panel. Simply connect the sample and drain lines, then the power and outputs, and it is ready to use. The product is calibrated at the factory before shipment, and additional calibrations are accomplished

by DPD comparison.

The analyser’s sensor technology and automatic pH compensation offer a reagentless design to keep the cost of ownership low without having expensive reagents.

It has automatic flow control and large flow tubes and cells, which reduces clogs and blockages and allows for easy cleaning.

The product includes dual 4–20 mA output, Modbus and/or HART communication and three alarm relay outputs. It can be powered from 24 VDC or 110/220 AC power. An auto cleaning option is available to keep the chlorine sensor clean from contaminants for an extended period of time.

AMS Instrumentation & Calibration Pty Ltd www.ams-ic.com.au

This issue is sponsored by | AMS Instrumentation & Calibration Solutions | www.ams-ic.com.au 23

what’s new

HEPA filter terminal housing The Camfil CleanSeal Extract Return Air Housing is designed for efficient air filtration systems.

The HEPA filter terminal housing features tool-less filter clamping, enabling a secure and quick installation process.

With quick grid locking, accessing the filter for maintenance or replacement is convenient and hassle-free. The fully welded construction of the housing offers long-lasting robustness and tightness, providing optimal protection against corrosion and decontamination agents.

One of the key benefits of the housing is its ability to offer localised control of potent compounds, preventing contamination of downstream ductworks. Additionally, the scanning system integrated into the design allows for easy operation and filter integrity testing. Suitable for a variety of applications in industries such as pharmaceuticals, hospitals and animal facilities, the housing offers a comprehensive solution for maintaining clean and healthy indoor air quality.

The CleanSeal Extract is part of the CleanSeal range designed with pre-positioning filter retainers and a patented adjustable clamping system to handle all Camfil Megalam filter sizes (MG/MD/MX). This scalability allows for fast and easy upgrade of existing filters to maintain pressure cascades or manage energy savings.

CleanSeal products are open to adaptation to the user’s specific needs, from additional features and functions to specific finishes, custom formats and fully bespoke ceiling integration.

Camfil Australia Pty Ltd www.camfil.com.au

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24 This issue is sponsored by | AMS Instrumentation & Calibration Solutions | www.ams-ic.com.au

pesticide

Sticky pesticide to protect crops from

insects

Thijs Bierman.

Dutch scientists have engineered a sticky substance that protects plants from diseases and pests by trapping them when they land on plant leaves, incapacitating them. The researchers hope that this ‘insect glue’, which they described in the journal PNAS, will help to reduce the use of toxic chemical pesticides.

I

Thrips caught in sticky droplets on a chrysanthemum leaf.

“The large drops are clearly more successful,”

n the search for alternatives to potentially

harmful chemical pesticides, scientists from

— although contact with food cannot be ruled out.

said Thijs Bierman, a PhD candidate at the Institute

“The advantage of our pesticide over chemical

of Biology Leiden. “Presumably, the thrips need to

pesticides is that you can see the small, yellow drops;

get stuck with a minimum body surface area. This

you can wash it off with water and dish soap,” Kodger

is also observed in carnivorous plants.”

said. If the substance is ingested, Kodger expects it

Wageningen University & Research (WUR) and

So far the scientists have mainly focused

to be no more harmful than frying fat, given that it

Leiden University turned to nature for inspiration.

on thrips, but the insect glue may also work

is derived from vegetable oil, but scientists still need

As explained by Thomas Kodger, an associate

against other pests, such as the Suzuki fruit fly

to investigate how (un)healthy it is exactly.

professor at WUR, “The carnivorous sundew plant

that currently threatens cherry cultivation. At

In the future, farmers may be able to spray

has so-called glandular hairs that secrete a sticky

the same time, the drops are small enough that

the sticky pesticide on their fields using existing

substance to catch insects. We wanted to mimic this

beneficial insects, such as pollinators, do not get

chemical sprayers, as a special additive in the

to protect our plants and crops in a natural way.”

stuck. Furthermore, pest insects are unlikely to

mixture ensures that the beads do not stick to

develop resistance against this adhesive.

each other or the machine. The researchers must,

The researchers transformed vegetable oil into a yellow, sticky substance by blowing air

“Insects have already evolved so that they

however, assess the environmental impact of this,

over it and grinding it into small particles using

avoid adhesion, for example through hairs on

as they would rather not dump large amounts of

a laboratory blender. This resulted in beads of

their body and a bumpy surface, [so] increasing

cooking oil onto the fields. They are also looking

about 1 mm in diameter that are as sticky as duct

their body size remains one of the few escape

to understand how the substance will affect the

tape, and similar in size to Californian thrips

methods from this sticky trap,” Kodger explained.

natural enemies of thrips, which are often used

(Frankliniella occidentalis) — common pest

This evolution is not nearly as easy as developing

by farmers for biological control.

insects that cause major problems worldwide in

tolerance to a chemical substance; it would take

In addition, the scientists are exploring

greenhouse horticulture.

many generations, if it happens at all, and would

possibilities to incorporate repellent or attractive

only occur if the insect glue is used on a large scale.

scents into the pesticide to make it even more

drops on plant leaves, with these drops catching

After application, the sticky substance remains

effective, and to utilise various waste oils based

the thrips inside them. By catching these insects,

on the leaves for three months, which is long

on availability, adapting their process accordingly.

plants stay healthier and are less likely to become

enough to control pests until harvest. By spraying

They aim to launch a spin-off company to further

infected with fungi that the thrips carry with them.

crops before the fruits develop, farmers minimise

develop and market their innovation, with plans

And the larger the drops, the greater the catch.

the chance of the pesticide getting onto the food

to start up by the end of the year.

The pesticide was sprayed as thick, sticky

This issue is sponsored by | AMS Instrumentation & Calibration Solutions | www.ams-ic.com.au 25

what’s new

High-throughput autoclave A quality autoclave is essential for almost any type of laboratory, and it is crucial for users to choose the product that will best suit their needs. Secure sterilisation and time savings are high priorities to consider for researchers, and TOMY autoclaves are designed with innovative features as standard.

The TOMY high-throughput autoclave FLS-1000 makes large-volume sterilisation easy and accommodates unusually shaped articles like bioreactors, fermenter vessels and animal cages. It also supports the user with secure sterilisation in compliance with their facility’s guidelines and global standards like GLP/GMP. no plumbing, so they can be moved to anywhere required. Two stainless steel

Next-generation gene editing platform

mesh baskets are included as standard and there is a range of accessories

The Horizon Discovery Pin-point Base Editing

available, including punched metal stainless steel baskets, solid stainless

platform from Revvity, with its novel three-part

steel baskets, printer and external sensor (wandering probe).

design and strong safety profile, is designed to

Key features include an integrated condensate bottle

enhance base editing’s capabilities by enabling

to trap condensate from a chamber during venting,

simultaneous modification of several genes at

full safety features including water level detec-

once, thereby expanding its application in hu-

tion and lid interlock, 100 L chamber capacity

man disease modelling.

The autoclaves are powered from a 240 V, 50 Hz, 15 A supply and require

for bulk or large-volume items and a maximum

Base editing is a CRISPR-Cas9-based

sterilising temperature to 123°C. The product is

technology that allows researchers to make

made in Japan.

precision base changes in genomic DNA.

Bio-Strategy - Part of DKSH Group

Editing with such precision can be used

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to silence disease-causing genes, correct disease-associated mutations and optimise cell therapies.

Pin-point base editing requires three key components: guide RNA with patented and proprietary aptamer; modified Cas9 (nickase

R-loop assay kit R-loops are three-stranded nucleic acid structures that are formed when a single-stranded RNA invades the DNA double helix to hybridise with a complementary DNA strand, leaving the non-template DNA strand unpaired. These structures form normally during transcription initiation, IgG class switching and mitochondrial DNA replication. R-loops play a role in chromatin dynamics and can also be used as biomarkers in some cancers.

The CUT&Tag-IT R-loop Assay Kit from Active Motif is optimised to profile R-loops genome-wide and has several advantages. It is designed to be faster and more efficient than DNA:RNA immunoprecipitation (DRIP) and chromatin immunoprecipitation (ChIP) methods, and is compatible with 200,000 to 500,000 fresh or cryopreserved cells. The kit comes with all reagents necessary, including an optimised protocol.

United Bioresearch Products Pty Ltd www.unitedbioresearch.com.au

Cas9, or nCas9); and deaminase fused to an aptamer binding protein. The gRNA guides the modified Cas9 to a specific location in the genome where a single strand ‘nick’ is made in the DNA. Meanwhile, the deaminase enzyme is recruited to the site and modifies bases on the non-nicked strand, for example, C>T conversions. The modified DNA strand is then used as a repair template for the nicked strand to complete the base pair conversion.

Compared to traditional CRISPR technologies that create double-stranded breaks in the DNA, base editing only nicks one strand of the DNA making it safer for therapeutic use. Key applications include: the creation of gene knock-out/SNP correction; proprietary concurrent knock-out and knock-in demonstrated; multiplexed gene editing for complex cell models; the ability to edit cells sensitive to the DNA damage response pathway; mutagenesis for functional gene characterisation; and orthogonal validation (RNAi, CRISPRi, traditional CRISPR/Cas9).

Millennium Science Pty Ltd www.mscience.com.au

26 This issue is sponsored by | AMS Instrumentation & Calibration Solutions | www.ams-ic.com.au

what’s happening

Coral-counting robot to assist with reef restoration Researchers at the Queensland University of Technology (QUT) have developed a robot to count and capture images of baby tank-grown corals destined for the Great Barrier Reef, saving thousands of hours of time.

It has been created as part of the Coral Growout Robotic Assessment System (CGRAS) project — a collaboration involving the Australian Institute for Marine Science (AIMS), the Reef Restoration & Adaptation Program (RR AP) and the QUT Research Engineering Facility (REF).

According to QUT’s Dr D o r i a n Ts a i, m o s t c o r a l restoration techniques are primarily focused on fragmenting existing corals — but this method is typically

submersible camera with a macroscopic lens — basically a waterproof

constrained to about 50 fragmented corals per origin or donor

microscope — mounted at the end of a robotic arm. The arm is

colony, limiting scalability.

wrapped up to prevent corrosion in the saltwater environment that is

“We’re aiming to mass-reproduce corals via sexual reproduction, where parent colonies can produce over a million corals each, which allows us to ensure the corals can diversify and adapt to changing environments, and has much better scalability,” Tsai said.

“The difficulty is that we have to then be able to grow and monitor these baby corals in order to keep the corals happy and healthy,

the aquaculture facility, and the whole thing is mounted atop a mobile platform that moves manually and houses all of the computers.

While the ideal approach could be to build a fully autonomous robot that could drive itself through the aquaculture facility, Tsai said that was not a cost-effective or necessary solution.

“Moving the robot manually between tanks only costs a fraction of the time compared to imaging, interpreting the images and counting

which CGRAS aims to solve.”

The challenge, Tsai explained, is that when the corals are grown

the corals,” he said.

en masse inside tanks on flat tiles, the corals are tiny — about 1 mm

“Furthermore, the costs, challenges and risks of a fully automated

in diameter. He noted, “There are hundreds of thousands of these

system for a still-developing coral conservation process are orders

corals, and it takes on average 45 minutes for a trained expert to

of magnitude more expensive than we currently have budget for.

count a single coral tile, which is 28 x 28 cm2. Eventually there will

“Instead, we aim to hit the sweet spot of what is achievable with a complement of robotics and humans together to maximise

be over 9600 such tiles.”

To count these corals manually, over 7200 hours would have to

operational and developmental costs for coral yield.”

be devoted to counting every week, which would be highly repetitive

Tsai said CGRAS was actively deployed in the National Sea

and end up costing around $500,000 per week in labour, or $6 million

Simulator (SeaSim) at AIMS near Townsville early this year, and

over a 12-week grow-out period.

its next iteration will be deployed for the next coral spawning in

“That’s why we’ve developed a robot prototype to capture images

December 2025. AIMS researchers will be the eventual operators

of the baby corals in the tanks as they are growing in a repeatable,

of the technology, as part of their efforts to help the Great Barrier

precise and flexible manner,” Tsai said.

Reef better cope with the effects of climate change.

“We’re also leveraging state-of-the-art artificial intelligence

“Projects like CGRAS are essential parts of the technology toolkit

algorithms to automatically detect and count these coral babies and

needed to deliver scale in this work,” said AIMS’s Research Program

track their growth over time.

Director of Reef Recovery, Adaptation and Restoration, Dr Line Bay.

“This will allow scientists to have a much clearer correlation

“We clearly need strong emissions reduction to provide the best

analysis between their treatment strategies and coral growth, leading

future for coral reefs. But with a fifth mass coral bleaching event

to higher coral survival rates, which is higher coral yield, which will

since 2016 unfolding on the Reef, research into restoration and

allow RRAP to reach their large-scale deployment scenarios of over

adaptation is also important.

a million corals out to the Great Barrier Reef each year.”

As explained by REF Senior Research Engineer Riki Lamont, the current design of the robot prototype houses a high-resolution

“Projects like this will turbo-charge R&D into conservation aquaculture methods that aim to help the Reef cope with increasing temperatures.”

This issue is sponsored by | AMS Instrumentation & Calibration Solutions | www.ams-ic.com.au 27

glucose testing

Smartphone compass used to measure glucose

I

iStock.com/Kosamtu

Researchers at the US National Institute of Standards and Technology (NIST) have used an ordinary smartphone’s built-in magnetometer, or compass, to measure concentrations of glucose — a key marker for diabetes. Described in the journal Nature Communications, their method also has the potential to measure other biomedical properties as well as environmental toxins.

Photograph of a prototype sensor platform attached to a phone. Image has been cropped from the original and appears courtesy of the study authors under CC BY 4.0

n their proof-of-concept study, NIST

react to a host

researchers Gary Zabow and Mark Ferris

of different

clamped to a smartphone a tiny well containing

compounds that

the solution to be tested and a strip of hydrogel

medical researchers

— a porous material that swells when immersed

may want to measure.

concentrations would allow

in water. The researchers embedded tiny

In their experiments, he and

measurements to be done

magnetic particles within the hydrogel, which

Zabow stacked single layers of two

with much less hassle,” Ferris

they had engineered to react either to the

different hydrogels, each of which

said. More generally, enhanced

presence of glucose or to pH levels by expanding

contracted and expanded at different rates

sensitivity would be essential when

or contracting. Changing pH levels can be

in response to pH or glucose. These bilayers

associated with a variety of biological disorders.

amplified the motion of the hydrogels, making

As the hydrogels enlarged or shrank,

it easier for the magnetometer to track changes

they moved the magnetic particles closer to

only a small amount of a substance is available for testing in extremely dilute quantities, Zabow added.

in magnetic field strength.

Similarly, the team’s study suggests that a

or further from the phone’s magnetometer,

Because the technique does not require any

phone magnetometer can measure pH levels with

which detected the corresponding changes in

electronics or power source beyond that of the

the same sensitivity as a thousand-dollar benchtop

the strength of the magnetic field. Employing

phone, nor call for any special processing of the

meter but at a fraction of the cost. A home-brewer

this strategy, the researchers measured glucose

sample, it offers an inexpensive way to conduct

or a baker could use the magnetometer to quickly

concentrations as small as a few millionths of a

testing — even in locations with relatively few

test the pH of various liquids to perfect their craft,

mole (the scientific unit for a certain number of

resources. Future efforts to improve the accuracy

and an environmental scientist could measure the

atoms or molecules in a substance). Although

of such measurements might allow detection of

pH of groundwater samples onsite with higher

such high sensitivity is not required for at-home

DNA strands, specific proteins and histamines

accuracy than a litmus test strip could provide.

monitoring of glucose levels using a drop of

— compounds involved in the body’s immune

In order to make the phone measurements

blood, it might in the future enable routine

response — at concentrations as low as a few tens

a commercial success, engineers will need to

testing for glucose in saliva, which contains a

of nanomoles (billionths of a mole). At present,

develop a method to mass produce the hydrogel

much smaller concentration of the sugar.

histamine measurement requires a 24-hour urine

test strips and ensure that they have a long shelf

‘Smart’ hydrogels like the ones the NIST team

collection and a sophisticated laboratory analysis.

life, Zabow said. The hydrogel strips should also be

employed are inexpensive and relatively easy

“An at-home test using a cellphone

designed to react more quickly to environmental

to fabricate, Ferris said, and can be tailored to

magnetometer sensitive to nanomolar

cues in order to speed up measurements, he added.

28 This issue is sponsored by | AMS Instrumentation & Calibration Solutions | www.ams-ic.com.au

SPONSORED CONTENT

Dissociation of tumor tissue samples for single-cell genomics Unraveling the diversity of cell types and understanding the complexity of the tumor microenvironment are critical milestones to advance cancer research and the development of both diagnostics and therapeutics for cancer.

Within the tumor microenvironment there are

scRNA-seq experiment. Ideally, the sample

numerous cells types, such as infiltrating

for a scRNA-seq experiment is a suspension

immune cells, inflammatory cells, cancer-

consisting of fully dissociated, intact, viable

associated fibroblasts, vascular cells, stromal

cells. Attributes of a poor quality sample include

cells, extracellular matrix, and tumor cells.

clumps, dead or dying cells, extracellular

Tumor cells are highly evasive due to their

debris, and ambient free-floating RNA. These

elasticity and ability to adapt to environmental

cellular and molecular contaminants can

modifications. As a result of these properties,

negatively impact data quality and increase

improving our understanding of a tumor’s

overall sequencing costs. Therefore, it is

dynamic

gene

important to consider the sample preparation

expression profile will enhance the research

process and utilize an approach that does not

community’s ability to develop more effective

produce a low-quality sample that adversely

diagnostics and treatments for cancer.

impacts scRNA-seq data.

cellular

composition

and

In recent years, single-cell RNA sequencing

To address this challenge, Miltenyi Biotec

(scRNA-seq) has become a popular analytical

and 10x Genomics designed a collaborative

tool to significantly augment characterization of

study to demonstrate the impact of sample

the tumor microenvironment. In contrast to RNA

preparation on scRNA-seq. For this work, our

sequencing of bulk cell populations, scRNA-

research teams combined methodologies for

seq allows for the transcriptomic profiling of

sample storage, tumor tissue dissociation,

hundreds, thousands, or potentially millions of

and sample cleanup from Miltenyi Biotec, with

individual cells. The ability to detect transcriptomic

the 10x Genomics technology for single-cell

signatures unique to an individual cell greatly

sequencing. As a result, we validated an end-

increases the diversity of transcripts that can be

to-end workflow for preparing solid tumor tissue

detected in a sample. This is in comparison to bulk

for single-cell RNA sequencing. For this study,

sequencing, whereby the average signal across

solid tumors from syngeneic mouse models

the entire sample obscures transcripts from rare

were collected and preserved in MACS® Tissue

cell populations. As a result, the use of scRNA-

Storage Solution, then dissociated using the

seq has the potential to facilitate advances, such

gentleMACS™ Octo Dissociator with Heaters

as the discovery of new cell subpopulations and

and the Tumor Dissociation Kit, mouse.

the identification of clonal tumor cell subsets

Following dissociation, a series of steps was

responsible for resistance to treatment.

performed to remove debris, red blood cells

The dissociation of a tumor in order to release

(RBCs), and dead cells prior to analysis of the

intact individual cells is a critical step in every

samples using the 10x Genomics Chromium

System and an Illumina sequencing platform.

Starting with the MACS Tissue Storage Solution for tumor sample collection and transport, followed by sample processing with gentleMACS Octo Dissociator with Heaters and the Tumor Dissociation kit, mouse, we were able to produce high quality single-cell suspensions with adequate performance in scRNA-seq. However, additional cleanup steps including RBCs and dead cell removal significantly improved different quality metrics for single-cell gene expression data generated using the 10x Genomics Chromium Platform.

Our data indicates that the reduction of RBCs and dead cells from the dissociated tumor tissue samples leads to: • An increased number of reads confidently mapped back to one cell • A higher number of genes detected per cell • Maximal cell recovery with the 10x Chromium System For all the details on this collaboration, please use the QR code

Miltenyi Biotec Australia Pty Ltd www.miltenyibiotec.com

This issue is sponsored by | AMS Instrumentation & Calibration Solutions | www.ams-ic.com.au 29

cancer treatment iStock.com/Nemes Laszlo

said. “In certain blood cancers where this response is suboptimal, STING agonists can supercharge this effect to deliver cancer a deathly blow.

“This is the one-two punch combo that could be the knockout blow for AML,” added co-first author Dr Sarah Diepstraten. “You could almost paraphrase the famous boxer Muhammed Ali and say this treatment floats like a butterfly and STINGs like a bee.”

Critically, the combination treatment showed promise in AML that was driven by a mutated p53 protein, which is generally more aggressive and harder to treat. The p53 protein is supposed to prevent the formation of cancerous cells by enforcing the death, or arresting the growth, of cells that have become damaged or abnormal —

One-two punch treatment

knocks out acute myeloid leukaemia

but when the protein is mutated and becomes defective in groups of cells, it can significantly boost a person’s risk of developing cancer.

“For AML patients that do not have as much therapy-induced death of their leukaemia cells due to this mutated protein, combining venetoclax with a STING agonist causes more killing of AML cells than treating with venetoclax alone,” Diepstraten said.

“The treatment was highly effective at killing cancer cells in samples with and without the p53 mutation, which is exciting given the lack of effective treatments for aggressive cancers driven by mutations in p53.”

WEHI lab head Professor Andrew Wei, co-senior author on the study, said that while further research is needed, the findings are

A novel combination of two cancer drugs has shown great potential as a future treatment for patients with acute myeloid leukaemia (AML), one of the most common types of blood cancer. The discovery, published in the journal Cancer Cell, could soon lead to clinical trials, providing hope for the 1100 Australians diagnosed with AML annually.

R

highly promising.

“While early clinical trials in solid cancers have suggested STING agonists are well tolerated in the body, these results offer exciting new hope for patients with the most resistant forms of leukaemia,” Wei said.

“Given STING agonists are currently in

esearchers at the Walter and

Eliza Hall Institute (WEHI) paired venetoclax, a current standard-of-care anticancer drug for AML, with a STING agonist, an emerging class of immunotherapy drug. This marks the first time that a STING agonist has been used to

tumours by activating the body’s immune

clinical trials, we hope to conduct human studies

response. But the new research indicates that

using STING agonists in combination with

they could be deployed against blood cancers,

venetoclax in the near future.

by directly targeting the cancer cells intrinsically.

“The research findings … will inspire a

The WEHI team examined samples from

completely new clinical approach for patients

a range of different blood cancers, including

affected by the most resistant and deadly forms

AML, and treated them in the lab with the drug

of acute leukaemia.”

combination. As explained by co-senior author

WEHI is now translating these findings into a

Associate Professor Gemma Kelly, a laboratory

new clinical trial in AML patients in collaboration

head in WEHI’s Blood Cells and Blood Cancer

with Aculeus Therapeutics, a local biotechnology

directly target mechanisms within the cancer cells

division, both venetoclax and the STING agonists

company which has spent the last several

themselves, stimulating the natural processes that

played complementary roles in killing the cancer

years developing a potent STING agonist. The

cause these cells to die.

at the cellular level.

proprietary drug, dubbed ACU-0943, is expected

Until now, STING agonist immunotherapy

“Within a cancer cell, venetoclax blocks the

drugs have been chiefly used to attack solid

machinery of the cell that is keeping it alive,” Kelly

to enter clinical development for the treatment of AML later this year.

30 This issue is sponsored by | AMS Instrumentation & Calibration Solutions | www.ams-ic.com.au

SPONSORED CONTENT

Is MMS the key to RNA analytics? istock.com/BlackJack3D

Introduction Riboswitches are small, well-folded mRNA sequences that regulate protein production by controlling the translation of specific mRNA segments. Each riboswitch has a unique small molecule that induces structural changes upon binding, activating the riboswitch. In this study, X-ray crystallography data and Microfluidic Modulation Spectroscopy (MMS) was used to characterise the structural changes of the SAM-I riboswitch upon ligand binding and determine the apparent dissociation constant (Kd). MMS provides a comprehensive understanding of RNA-ligand binding and structural changes, offering potential for developing novel small molecule

allosteric communication pathways. However, these techniques only provide either structural information or binding information on the RNAligand complex.

In this study, MMS was used to study the structural changes of the SAM-I riboswitch upon binding. MMS probes the nucleic acid bases in the Amide-I IR range to examine base pairing and stacking during RNA folding and unfolding.

This technique provides real-time background correction, making it useful for quality control and compatible with various formulation buffers.

The Apollo MMS system, equipped with a highpower Quantum Cascade Laser, was used for this study, offering greater sensitivity compared to traditional FTIR and CD methods.

RNA regulators for therapeutic purposes.

Background RNA molecules play versatile roles beyond mediating gene expression. RNA riboswitches are critical regulatory components that govern gene expression in response to small molecule through riboswitches can reveal gene regulation mechanisms for targeted therapeutics.

The

S-adenosylmethionine regulates

gene

(SAM)-I

expression

in

response to intracellular SAM concentrations.

SAM is a key metabolite involved in various cellular processes, including transmethylation, transsulfuration,

and

polyamine

synthesis.

The SAM-I riboswitch comprises an aptamer domain for SAM recognition and a downstream expression platform governing gene expression.

Upon SAM binding, the aptamer domain undergoes

conformational

rearrangements,

transmitting signals to modulate transcriptional or translational outputs.

MMS spectra (Similarity plot) is used to quantitate similarity between samples.

Methods SAM-I riboswitches (apo and ligand-bound) were obtained from Arrakis (Waltham, MA). The RNA samples were buffer-exchanged to their formulation buffer and run in triplicate on the Apollo MMS system at a concentration of 0.67 mg/mL (22 µM). A backing pressure of 5 psi was used to move the samples into the flow cell, where they were modulated at 1 Hz between sample and reference buffer for background subtraction.

Study Overview

MMS results indicated subtle but detectable structural changes due to ligand binding on the SAM-I riboswitch. Specific peaks in the spectra corresponded to changes in base pairing and stacking, with notable changes observed at 1690, 1640–1670, and 1604 cm-1. These peaks were primarily assigned to guanine, uracil/ cytosine, and adenine, respectively. A dosedependent titration of SAM into the SAM-I riboswitch demonstrated gradual spectral changes, suggesting guanine base-pairing and interactions with adenine residues.

The spectral changes observed were significant, indicating conformational changes in the RNA due to ligand binding. A plot of the spectral difference showed that changes plateaued at around 20 µM SAM concentration, suggesting a 1:1 ligand-to-riboswitch molar ratio.

This study demonstrated MMS as a quick and effective tool to detect structural changes and determine Kd values for RNA-ligand binding.

Conclusions

ligands. Understanding RNA-ligand binding

riboswitch

Results and Discussion

Differential absorbance was measured between

Structural studies of the SAM-I riboswitch have

1580–1765 cm-1. Data processing involved

provided insights into RNA-ligand interactions.

converting

Techniques such as X-ray crystallography, NMR

absorbance, normalising by concentration and

spectroscopy, and cryo-electron microscopy

optical pathlength, and analysing the second

have detailed the SAM-binding pocket and

derivatives of the spectra.

raw

absorbance

to

This work highlighted MMS as a viable orthogonal assay for detecting RNA structural changes in the presence of small molecule ligands. It also demonstrated the potential of MMS to determine the apparent Kd of RNA-ligand binding in the micromolar range, sensitively distinguishing structural changes in the RNA riboswitch due to ligand binding.

For more information, please contact ATA Scientific Pty Ltd (phone: +61 2 9541 3500, email: enquiries@atascientific.com.au and website: www.atascientific.com.au) 1. Huang, R., & Colins, V. (2024, May 8). Structural Characterization of RNA and Detection of RNA-ligand Binding Using Microfluidic Modulation Spectroscopy.

Redshiftbio.com. Retrieved May 23, 2024, from https://www.redshiftbio.com/resources/structuralcharacterization-of-rna-and-detection-of-rna-ligandbinding-using-microfluidic-modulation-spectroscopy

absolute ATA Scientific Pty Ltd www.atascientific.com.au

This issue is sponsored by | AMS Instrumentation & Calibration Solutions | www.ams-ic.com.au 31

Coin-sized device can isolate plasma, replacing centrifuges

Scientists at Nanyang Technological University, Singapore (NTU Singapore) have developed a coin-sized chip that can directly isolate plasma from a tube of blood in just 30 min, which is more convenient and user-friendly than the current gold-standard, multi-step centrifugation process.

N

amed ExoArc and described in the

journal ACS Nano, the chip can achieve high blood plasma purity by removing more than 99.9% of blood cells and platelets precisely and gently in just one step. This should greatly speed up clinical analysis of the cell-free DNA and RNA molecules as well as extracellular vesicles, which are often used to screen for biomarkers that are telltale signs specific to certain cancers and diseases.

The current gold-standard method of isolating blood plasma relies on a centrifuge, which spins blood samples at high speeds, separating the blood cells from the plasma. But even after two rounds of spinning in the centrifuge, which can take up to an hour, there will still be some cells and platelets present in the blood plasma which can break down or degrade, leading to unwanted materials that affect the accuracy of diagnostic tests. This is one of the reasons that blood tests are time-sensitive, requiring processing within a day or even a few hours to prevent this rapid degradation of biological material.

Laboratories typically wait to accumulate multiple blood samples before using the centrifuge, extending the isolation process by several hours. This delay, combined with the extended duration of centrifugation and operator variability, sometimes makes it challenging to compare scientific findings between different research labs. Associate Professor Hou Han Wei, lead scientist on the new study, said the NTU team aimed to find a quicker solution that could replace the centrifuge, while still yielding highquality plasma for disease screening and research.

iStock.com/Fly_dragonfly

“It has been nearly 160 years since the invention of the first centrifuge and about 50 years since modern high-speed centrifuges became a standard tool in laboratories for preparing blood samples,” Hou said. “Despite these advancements, separating complex liquids like blood, which

32 This issue is sponsored by | AMS Instrumentation & Calibration Solutions | www.ams-ic.com.au

plasma isolation

the isolated blood plasma. Unlike a

molecules from blood plasma samples from healthy

centrifuge, which usually processes

individuals and those with type 2 diabetes mellitus

multiple tubes of blood samples,

using quantitative polymerase chain reaction

ExoArc technology can be scaled

(PCR). From just one tube of blood, they identified

up by designing multiple channels

293 different microRNA molecules. The research

to simultaneously isolate blood

team also found that the microRNA profile from

plasma as and when blood samples

plasmas and extracellular vesicles from individuals

are received in clinics or hospitals in

with type 2 diabetes had a different composition

a faster and more consistent manner.

as compared to healthy participants. This suggests

Together with clinician-

the potential of ExoArc in helping to isolate and

scientists from the National Cancer

Assoc Prof Hou Han Wei holding the patent-pending ExoArc chip, which uses microfluidic channels to separate the blood plasma from the blood cells and platelets.

identify disease-related biomarkers.

Centre Singapore (NCCS), Tan

Associate Professor Rinkoo Dalan, Senior

Tock Seng Hospital (TTSH) and

Consultant specialising in diabetes and

the Agency for Science, Technology

endocrinology at TTSH, said the initial results

and Research (A*STAR), the team

are promising and show the potential of ExoArc

clinically validated ExoArc by

being able to help drive precision medicine.

comprises various cell types and a diverse range

analysing the microRNA profile of blood plasma

“This technology can help clinicians better

of biological materials, remains a challenge.

in healthy people and cancer patients using a

predict and manage complications of chronic

“By leveraging unique flow phenomenon in

biomarker panel and found it was able to diagnose

metabolic conditions like diabetes, by providing more

tiny channels in a chip that is about the size of a

non-small cell lung cancer with a sensitivity of

accurate, timely and individualised information,”

dollar coin, we can now efficiently separate small

90%. Co-author Professor Darren Lim, Senior

Dalan said. “By detecting specific biomarkers

biological materials based on their size without

Consultant in the Division of Medical Oncology

accurately, we can tailor treatments to the unique

using any physical membrane or filters. We have

at NCCS, said reducing contamination from

needs of each patient, potentially improving

transformed this breakthrough technology into a

degraded blood cells is crucial for the accuracy

outcomes and enhancing the quality of care.”

device about the size of a small desktop printer,

of diagnostic tests.

contamination in clinical testing.”

With two patent applications now filed for

“Our study shows that this device allows

the ExoArc innovation through NTUitive, NTU’s

quicker and more precise clinical diagnoses,

innovation and enterprise company, it is believed

featuring disposable plastic chips to prevent crossAs a proof of concept, the NTU team built a

significantly decreasing the waiting time for test

that the method has the potential to significantly

portable prototype device (measuring 30 x 20 x 30

results, reducing patients’ anxiety and ultimately

reduce the time needed to prepare samples for

cm) to house the ExoArc chip (3.5 x 2.5 x 0.3 cm),

improving their overall care,” Lim said. “This is

testing and streamline diagnostics, potentially

which has a large touch-screen interface to adjust

particularly significant for cancer treatment.”

helping to reduce overall cost. By adjusting the

settings, as well as internal pumps and pipings for

In another demonstration of its application,

size cut-off, the platform can also be used to isolate

the processing of blood samples and collection of

the team used ExoArc to study microRNA

bacteria or viruses from blood or other biofluids.

Total organic carbon analyser Beckman Coulter Life Sciences’ QbD1200+ Total Organic Carbon (TOC) Analyzer, offering simplified validation and reporting on encrypted data, is designed to support 21 CFR Part 11 requirements and major global pharmacopeia regulations: USP, EP, JP, IP and KP. The product has been designed to make measuring and analysing total organic carbon simple, reproducible and intuitive, all with one reagent.

The analyser features a digital non-dispersive infrared sensor (NDIR) with auto-correct drift to provide long-term stability. It delivers reproducible results with control of the UV reactor temperature, dynamic endpoint detection and reduced sample-to-sample carryover. To help minimise maintenance and simplify workflows, seven different sensors enable automatic system checks each time the instrument is powered on and monitor the instrument continuously.

An active directory allows encrypted data to be exported to a shared network directory to keep auditable information safe, secure and paperless without the need for a PC. The intuitive user interface, along with the large colour touchscreen, facilitates daily operations, simplifying workflows and making the product easy to use while reducing the need for intensive personnel training in laboratories.

Beckman Coulter Australia www.beckman.com.au This issue is sponsored by | AMS Instrumentation & Calibration Solutions | www.ams-ic.com.au 33

event horizon

Biomolecular Horizons 2024

ASM National Meeting 2024 July 1–4, Brisbane www.theasmmeeting.org.au Joint AAAP & AAAS Animal Production Congress 2024 July 9–12, Melbourne www.aaap2024.com 72nd CSANZ Annual Scientific Meeting August 1–4, Perth www.csanzasm.com AIFST24 Convention August 6–7, Sydney www.aifst.asn.au/AIFST24-Convention Ending Plastic Waste Symposium 2024 August 6–7, Melbourne events.csiro.au/Events/2024/May/3/Ending-PlasticWaste-Symposium-2024 Beaker Street Festival 2024 August 6–13, Hobart www.beakerstreet.com.au National Science Week 2024 August 10–18, Australia-wide www.scienceweek.net.au The XVIth Quark Confinement and the Hadron Spectrum Conference August 19–24, Cairns confinement24.org.au AIMS National Scientific Meeting August 21–23, Adelaide aimsnsm2024.com Acoustics 2024 — The Acoustical Society of New Zealand September 2–4, Christchurch www.acousticsnz2024.co.nz ASCIA 2024 Conference September 3–6, Adelaide and online ascia2024.com

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This will be the first time the IUBMB Congress will be held in Melbourne and only the third time in the Southern Hemisphere. It will join with FAOBMB and ComBio to create a truly global forum bringing together renowned scientists from across the world, from Nobel laureates to early-career scientists. The overarching theme of the forum is ‘Discover, Create, Innovate’. www.bmh2024.com/

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