Posted in | Biosensors

Adopting Nanoplasmonic Materials for Real-Time Monitoring of Processes in Living Cells

Members of the Micro/Bio/Nanofluidics Unit showcase their nanoplasmonic materials. From left: Nikhil Bhalla, Shivani Sathish, and Amy Shen. (Credit: OIST)

On Professor Amy Shen’s desk is a small rectangular pink glass, approximately the size of a postage stamp. Although it looks simple from outside, the small glass slide has the ability to entirely transform a broad array of processes, such as diagnosing diseases and monitoring food quality.

A ‘nanoplasmonic’ material has been used to develop the slide, where the surface of the material is formed of millions of gold nanostructures. The size of each nanostructure is a few billionths of 1 m2. The distinctive sensing characteristics of plasmonic materials are due to their ability to absorb light and scatter it in intriguing ways. Nanoplasmonic materials have gained the attention of chemists, biologists, material scientists, and physicists, with prospective applications in a range of fields, for example, data storage, biosensing, solar cells, and light generation.

In many papers published recently, Professor Shen and her collaborators at the Micro/Bio/Nanofluidics Unit at the Okinawa Institute of Science and Technology (OIST) outlined the development of an innovative biosensing material that can be used to observe processes that take place in living cells.

One of the major goals of nanoplasmonics is to search for better ways to monitor processes in living cells in real time.

Professor Shen, Okinawa Institute of Science and Technology (OIST)

Gathering such information can disclose hints in cell functioning; however, it is difficult to develop nanomaterials on which cells can sustain for longer time periods yet do not intrude into the cellular processes that are evaluated measured, Shen explained.

Counting Dividing Cells

One of the innovative biosensors developed by the team is formed of a nanoplasmonic material with the potential to incorporate more cells on a single substrate and to observe, in real time, cell proliferation, a basic process that involves cell growth and division. Observing the process in real time can provide significant knowledge of the health and functions of cells and tissues.

Recently, scientists in OIST’s Micro/Bio/Nanofluidics Unit reported about the sensor in a research published in the Advanced Biosystems journal.

The most striking property of the material is that it enables cells to survive for longer periods of time.

Usually, when you put live cells on a nanomaterial, that material is toxic and it kills the cells. However, using our material, cells survived for over seven days.

Dr Nikhil Bhalla, Postdoctoral Researcher, Okinawa Institute of Science and Technology

The nanoplasmonic material also has high sensitivity—it has the ability to detect an increase in the number of cells as less as 16 in 1000 cells.

Although the material exactly resembles an ordinary glass piece, tiny nanoplasmonic mushroom-like structures, or nanomushrooms, are coated on its surface. The stems of the nanomushrooms are made of silicon dioxide and their caps are made of gold. Jointly, the stem and the cap form a biosensor with the ability to detect molecular-scale interactions.

The nanomushroom caps are used as optical antennae for the functioning of the biosensor. When white light enters the nanoplasmonic slide, the nanomushrooms absorb light and scatter a portion of it, thereby modifying its characteristics. The shape, size, and material of the nanomaterial govern the absorbing and scattering of light, which is also influenced by any medium positioned nearer to the nanomushroom, for example, cells placed on the slide. The scientists can detect and observe processes (for example, cell division) that take place on the sensor surface by evaluating the change in the nature of light when it emerges from the other side of the slide.

Normally, you have to add labels, such as dyes or molecules, to cells, to be able to count dividing cells. However, with our method, the nanomushrooms can sense them directly.

Dr Nikhil Bhalla, Postdoctoral Researcher, Okinawa Institute of Science and Technology

Scaling Up

This study is based on an innovative technique, devised by researchers from the Micro/Bio/Nanofluidics Unit at OIST, for creating nanomushroom biosensors. The technology was reported in ACS Applied Materials and Interfaces in December 2017.

Development of large-scale nanoplasmonic materials is difficult because it is challenging to ensure uniformity over the total surface of the material. Hence, there is a lack of biosensors for standard clinical examinations, for example, disease testing.

To overcome this difficulty, the OIST scientists devised an innovative printing method for developing large-scale nanomushroom biosensors. By using their technique, they could create a material including about one million mushroom-like structures on a silicon dioxide substrate with dimensions of 2.5 cm by 7.5 cm.

Our technique is like taking a stamp, covering it with ink made from biological molecules, and printing onto the nanoplasmonic slide,” stated Shivani Sathish, co-author of the study, who is a PhD student at OIST. The biological molecules enhance the sensitivity of the material, suggesting that it has the ability to sense very low concentrations of substances (e.g. antibodies), and thus prospectively detect diseases in their benign stages.

Using our method, it is possible to create a highly sensitive biosensor that can detect even single molecules,.

Dr Nikhil Bhalla, Postdoctoral Researcher, Okinawa Institute of Science and Technology

Plasmonic and nanoplasmonic sensors can prove to be significant tools for many fields such as food production, electronics, and medicine. For instance, in December, 2017, Ainash Garifullina, second-year PhD student from the Unit, created an innovative plasmonic material for observing the quality of food products while manufacturing. The outcomes of that study were reported in the Analytical Methods journal.

Professor Shen and her team stated that in the future, nanoplasmonic materials might even be combined with emerging technologies (for example, wireless systems in microfluidic devices), enabling users to remotely register readings and hence reducing the contamination risks.

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