Tag Archives: Indian Institute of Science (IISc)

Scientists at Indian Institute of Science (IISc) created hybrid nanoparticles made of gold and copper sulfide that can kill cancer cells

It’s been a while since there was a theranostic (diagnosis and therapy combined in one treatment) story here.

Caption: Schematic indicating photo-theranostic potential of TSP-CA Credit: Madhavi Tripathi

A September 11, 2023 news item on phys.org announces the research, Note: A link has been removed,

Scientists at the Indian Institute of Science (IISc) have developed a new approach to potentially detect and kill cancer cells, especially those that form a solid tumor mass. They have created hybrid nanoparticles made of gold and copper sulfide that can kill cancer cells using heat and enable their detection using sound waves, according to a study published in ACS Applied Nano Materials.

A September 11, 2023 Indian Institute of Science (IISC) press release (also on EurekAlert), which originated the news item, provides more detail about the research,

Early detection and treatment are key in the battle against cancer. Copper sulphide nanoparticles have previously received attention for their application in cancer diagnosis, while gold nanoparticles, which can be chemically modified to target cancer cells, have shown anticancer effects. In the current study, the IISc team decided to combine these two into hybrid nanoparticles.  

“These particles have photothermal, oxidative stress, and photoacoustic properties,” says Jaya Prakash, Assistant Professor at the Department of Instrumentation and Applied Physics (IAP), IISc, and one of the corresponding authors of the paper. PhD students Madhavi Tripathi and Swathi Padmanabhan are co-first authors.

When light is shined on these hybrid nanoparticles, they absorb the light and generate heat, which can kill cancer cells. These nanoparticles also produce singlet oxygen atoms that are toxic for the cells. “We want both these mechanisms to kill the cancer cell,” Jaya Prakash explains.  

The researchers say that the nanoparticles can also help diagnose certain cancers. Existing methods such as standalone CT and MRI scans require trained radiology professionals to decipher the images. The photoacoustic property of the nanoparticles allows them to absorb light and generate ultrasound waves, which can be used to detect cancer cells with high contrast once the particles reach them. The ultrasound waves generated from the particles allow for a more accurate image resolution as sound waves scatter less when they pass through tissues compared to light. Scans created from the generated ultrasound waves can also provide better clarity and can be used to measure the oxygen saturation in the tumour, boosting their detection.

“You can integrate this with existing systems of detection or treatment,” says Ashok M Raichur, Professor at the Department of Materials Engineering, and another corresponding author. For example, the nanoparticles can be triggered to produce heat by shining a light on them using an endoscope that is typically used for cancer screening. 

Previously developed nanoparticles have limited applications because of their large size. The IISc team used a novel reduction method to deposit tiny seeds of gold onto the copper sulphide surface. The resulting hybrid nanoparticles – less than 8 nm in size – can potentially travel inside tissues easily and reach tumours. The researchers believe that the nanoparticles’ small size would also allow them to leave the human body naturally without accumulating, although extensive studies have to be carried out to determine if they are safe to use inside the human body.  

In the current study, the researchers have tested their nanoparticles on lung cancer and cervical cancer cell lines in the lab. They now plan to take the results forward for clinical development.  

Here’s a link to and a citation for the paper,

Seed-Mediated Galvanic Synthesis of CuS–Au Nanohybrids for Photo-Theranostic Applications by Madhavi Tripathi, Swathi Padmanabhan, Jaya Prakash, and Ashok M. Raichur. ACS Appl. Nano Mater. 2023, 6, 16, 14861–14875 DOI: https://doi.org/10.1021/acsanm.3c02405 Publication Date:August 10, 2023 Copyright © 2023 American Chemical Society

This paper is behind a paywall.

A brainlike (neuromorphic) camera can go beyond diffraction limit of light

Just when I think I’m getting caught up with my backlog along comes something like this. A February 21, 2023 news item on Nanowerk announces research that combines neuromorphic (brainlike) engineering and nanotechnology, Note: A link has been removed,

In a new study, researchers at the Indian Institute of Science (IISc) show how a brain-inspired image sensor can go beyond the diffraction limit of light to detect miniscule objects such as cellular components or nanoparticles invisible to current microscopes. Their novel technique, which combines optical microscopy with a neuromorphic camera and machine learning algorithms, presents a major step forward in pinpointing objects smaller than 50 nanometers in size.

A February 21, 2023 (?) Indian Institute of Science (IISc) press release (also on EurekAlert), which originated the news item, describes the nature of the task and provides some technical details,

Since the invention of optical microscopes, scientists have strived to surpass a barrier called the diffraction limit, which means that the microscope cannot distinguish between two objects if they are smaller than a certain size (typically 200-300 nanometers). Their efforts have largely focused on either modifying the molecules being imaged, or developing better illumination strategies – some of which led to the 2014 Nobel Prize in Chemistry. “But very few have actually tried to use the detector itself to try and surpass this detection limit,” says Deepak Nair, Associate Professor at the Centre for Neuroscience (CNS), IISc, and corresponding author of the study.  

Measuring roughly 40 mm (height) by 60 mm (width) by 25 mm (diameter), and weighing about 100 grams, the neuromorphic camera used in the study mimics the way the human retina converts light into electrical impulses, and has several advantages over conventional cameras. In a typical camera, each pixel captures the intensity of light falling on it for the entire exposure time that the camera focuses on the object, and all these pixels are pooled together to reconstruct an image of the object. In neuromorphic cameras, each pixel operates independently and asynchronously, generating events or spikes only when there is a change in the intensity of light falling on that pixel. This generates sparse and lower amount of data compared to traditional cameras, which capture every pixel value at a fixed rate, regardless of whether there is any change in the scene. This functioning of a neuromorphic camera is similar to how the human retina works, and allows the camera to “sample” the environment with much higher temporal resolution – because it is not limited by a frame rate like normal cameras – and also perform background suppression.  

“Such neuromorphic cameras have a very high dynamic range (>120 dB), which means that you can go from a very low-light environment to very high-light conditions. The combination of the asynchronous nature, high dynamic range, sparse data, and high temporal resolution of neuromorphic cameras make them well-suited for use in neuromorphic microscopy,” explains Chetan Singh Thakur, Assistant Professor at the Department of Electronic Systems Engineering (DESE), IISc, and co-author. 

In the current study, the group used their neuromorphic camera to pinpoint individual fluorescent beads smaller than the limit of diffraction, by shining laser pulses at both high and low intensities, and measuring the variation in the fluorescence levels. As the intensity increases, the camera captures the signal as an “ON” event, while an “OFF” event is reported when the light intensity decreases. The data from these events were pooled together to reconstruct frames. 

To accurately locate the fluorescent particles within the frames, the team used two methods. The first was a deep learning algorithm, trained on about one and a half million image simulations that closely represented the experimental data, to predict where the centroid of the object could be, explains Rohit Mangalwedhekar, former research intern at CNS and first author of the study. A wavelet segmentation algorithm was also used to determine the centroids of the particles separately for the ON and the OFF events. Combining the predictions from both allowed the team to zero in on the object’s precise location with greater accuracy than existing techniques.  

“In biological processes like self-organisation, you have molecules that are alternating between random or directed movement, or that are immobilised,” explains Nair. “Therefore, you need to have the ability to locate the centre of this molecule with the highest precision possible so that we can understand the thumb rules that allow the self-organisation.” The team was able to closely track the movement of a fluorescent bead moving freely in an aqueous solution using this technique. This approach can, therefore, have widespread applications in precisely tracking and understanding stochastic processes in biology, chemistry and physics.  

Caption: Transformation of cumulative probability density of ON and OFF processes allows localisation below the limit of classical single particle detection. Credit: Mangalwedhekar et al

Here’s a link to and a citation for the paper,

Achieving nanoscale precision using neuromorphic localization microscopy by Rohit Mangalwedhekar, Nivedita Singh, Chetan Singh Thakur, Chandra Sekhar Seelamantula, Mini Jose & Deepak Nair. Nature Nanotechnology volume 18, pages 380–389 (2023) DOI: https://doi.org/10.1038/s41565-022-01291-1 Published online: 23 January 2023 Issue Date: April 2023

This paper is behind a paywall.