Low-cost technology for mass production of arrayed miniaturised experiments

Life is complex. Tens of thousands of genes form the blueprint for every human cell, and 200 cell types form the thousand  billion cells that make up  a human being. Life’s complexity is the reason why the CSIR has developed technology to investigate cells themselves, faster than ever previously possible.

Researchers and pharmaceutic al companies are interested in knowing how cells work, how they interact and how pathogens interact with them. These interactions form the basis of most diseases afflicting society. If they can be understood and ultimately treated, then our quality of life will improve. But this is challenging – any one of thousands of human genes can fail and cause disease, yet a pathogen can find its way into cells using only a handful of genes. This article describes new miniaturised technology to confront this challenge and  that is being spun out from the CSIR.
Complexity comes at a price. Having 20 000 genes to study means many times the number of genes in experiments. This means that human beings can no longer do all these experiments. Biologists have adopted automation technology and robotics from the pharmaceutical industry to do all these experiments and now large industrial and academic centres
worldwide are performing these screens, looking to find new understanding and new drugs.

The current technology is powerful, but that comes with the corollary of how long a single screening experiment takes.
Even with robotics, automation and a team of scientists, one screening experiment takes from four to six weeks of full-time work. Screening is also limited to a handful of research centres  – mostly in the developed world– and requires a complex, fixed infrastructure. This makes the  technology limited in application and technologically demanding. Given how hard this is, our approach is to miniaturise it all and fit thousands of experiments into a handheld device.

Miniaturisation permeates our lives – we all understand the benefits. Miniaturisation of devices dates to the invention of the pocket watch in the 16th century by Peter Heinlein.

While driven by necessity, miniaturisation’s greater impact came with mass production. Large-scale production gave us lots of relatively inexpensive devices – such as the pocket calculator. The twin impact of miniaturisation and mass production impacts all aspects of modern life, business and research.

The CSIR’s high throughput biology group, under leadership of Dr Neil Emans, has developed new technology that
miniaturises experiments and makes the task of finding new cures easier. This technology is incorporated in Persomics, a new technology start-up company.

Persomics technology works through array printing technology, which prints thousands of experiments onto a device. Each experiment is tiny – the width of a pencil tip – and yet each one is one of thousands of experiments, and these are enough to use to screen how cells work and understand how disease progresses. Screening thousands of experiments with cells this way is at least a hundred fold faster than previous technology and can be mass produced for the first time.  Fanie Marais, CSIR commercialisation manager in the biosciences domain, says: “This novel technology enables the printing of an entire array of experiments at the same time,  reducing the time and cost of cell-based screening through miniaturisation, literally creating a mass production pipeline.”

Mass miniaturisation

Miniaturisation is used to shrinkgene silencing experiments from the macroscale to the miniature. Each experiment is printed onto a glass wafer, as a spot of gene-silencing  chemistry only 300 millionths of a metre wide. A single printed experiment recapitulates all the features of a macro-experiment. The partner technology used focuses on scaling this up – producing thousands of these experiments printed as arrays on a glass wafer.

Life sciences and medicine are moving towards large-scalebiology, high-content, cellbased screening. Miniaturised,
commoditised screening tools access this space without the need for complex robotics on a wider customer base.

“The technology provides the means to bring libraries and experiments from plates to an imaging-ready microtiter plate
packed with 3 000 experiments for clients. Clients will get these ready for screening and at an industrial scale of thousands,” says Marais.

The currently available solutions involve high-throughput, plate-based screening of largescale installations, producing
screening at a high cost with limited access and impact. It also involves the use of arrayed screens with no commercial
solution; has a labour-intensive set-up; and is miniaturised,  but not scaled to market or personalised medicine needs.
“The fact that we are able to produce these devices provides us with an opportunity to further investigate diseases to
better understand how infection proceeds and how exactly it can be cured,” concludes Marais.

Creating new markets
The human genome is at the leading edge of modern lifesciences, enabled by genome- scaled experiments. But the size of the human genome is a bottleneck, slowing the introduction of screening which creates an opportunity for making array screening technology available to the market. It is believed that miniaturisation, and mass production of Omic devices will create new markets in research and health care.

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