Micro/Nanoscale

Mechanical engineering professor asserts that “size matters” when it comes to microscale sensors and machines

Anonymous — Wed, 13 Oct 2021 20:01:27 +0000

Mechanical engineering professor asserts that “size matters” when it comes to microscale sensors and machines Anonymous (not verified) Wed, 10/13/2021 - 14:01

Victor M. Bright of the Paul M. Rady Department of Mechanical Engineering will deliver his Distinguished Research Lecture “Microscale Sensors and Machines—Size Matters!” virtually on Tuesday, November 2 from 4–5 p.m.

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Ding lab aims to improve cancer-fighting immunotherapies with $1.8M grant

Anonymous — Wed, 28 Jul 2021 17:39:41 +0000

Ding lab aims to improve cancer-fighting immunotherapies with $1.8M grant Anonymous (not verified) Wed, 07/28/2021 - 11:39

Catherine Arnold

Above: Members of the Ding research lab gather for a team hike. Top: A typical microfluidic device for drug delivery treatment capable of treating millions of cells within one minute. In this device, immune cells are loaded through an inlet needle and collected from the outlet needle.

Professor Xiaoyun Ding recently earned a $1.8 million grant from the National Institutes of Health (National Institute of General Medical Sciences) to help improve cancer-fighting tools and cut patient costs, exploring ways to streamline delivery of lifesaving treatments into immune cells.

“This funding has the perfect timing to help expand our research,” said Ding.

With current immunotherapy treatments, when disease-fighting white blood cells called T-cells tire and can no longer seek out and destroy cancer cells, modified forms of those cells can be introduced to help the body treat itself. But it’s an imprecise and costly procedure.

Started July 1, the five-year award supports the Ding Lab’s efforts to learn how to efficiently and precisely disrupt cell membranes so that treatment can be introduced to improve cell function, as well as how to repair the membranes faster. In particular, the researchers will attempt to standardize a process that can be automated for millions of cells in a second.

In previous research, Ding’s lab found that they could use microfluidic technology to disrupt the membrane, deliver molecules into the cell and control the dose. They also showed it’s possible to deliver DNA molecules into the cell, a process not achievable in other ways through membrane disruption.

The results are not yet precise enough for commercial use — the mechanisms of cell membrane disruption and cell response to such disruption are not entirely clear — so the team will investigate the process behind controlling doses. They’ll learn whether the procedure becomes more efficient when they monitor the size and number of “pores” at the cell membrane of a cell, for instance.

Conducting interdisciplinary research at the frontiers of biology, medicine, physics and micro/nano engineering, Ding’s group will work to develop technological devices that can disrupt cell membranes to deliver controllable doses to cells through a certain number of pores—treating mainly targeted cell areas and killing fewer healthy cells.

The team will also attempt to control the cell membrane disruption and how quickly it recovers from rupture after treatment is delivered. Because an individual cell will die if its membrane is disrupted too much, the researchers plan to learn what level of disruption they can achieve safely and when they should stop. They’d also like to glean ways to help cells recover to create a stronger rupture that can be repaired later, said Ding.

His lab achieved promising earlier findings in their investigation of cell behavior, including a 2020 discovery that allowed them to diagnose sickle cell disease with greater sensitivity and precision in less than one minute.

Speedy processing could also improve treatment costs for cancer and other diseases.

The principal investigator on this NIH grant, Ding started his academic studies in microelectronic and mechanical engineering.

Focusing on technology development, he looked for applications for the work. Then he realized that was not the best approach, recognizing that drug delivery is a broad category and depends on each disease and its applications. So as a postdoc pursuing chemical and biomedical engineering learning in immunotherapy, he absorbed medical problems first, then developed strategies to deliver treatment for them.

“I want to deliver treatment at high efficiency and with low costs. That’s the goal. I’m working in problem-driven research,” Ding said.

Ding’s lab also does research on Lab-on-a-Chip technologies for micro/nano manipulation, cell mechanics and fast diagnosis.

The goal of the NIH Maximizing Investigators’ Research Award is to increase the efficiency of National Institute of General Medical Sciences funding by providing investigators with greater stability and flexibility, thereby enhancing scientific productivity and the chances for important breakthroughs. This grant is believed to be the first MIRA granted to anyone in the Paul M. Rady Department of Mechanical Engineering.

Professor Xiaoyun Ding recently earned a $1.8 million grant to help improve cancer-fighting tools and cut patient costs, exploring ways to streamline delivery of lifesaving treatments into immune cells.

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Researchers scale up tiny actuator inspired by muscle

Anonymous — Thu, 12 Nov 2020 17:38:38 +0000

Researchers scale up tiny actuator inspired by muscle Anonymous (not verified) Thu, 11/12/2020 - 10:38

Oksana Schuppan

Researchers at ŷ��ڱ��Ƶ Boulder are collaborating to develop a new kind of biocompatible actuator that contracts and relaxes in only one dimension, like muscles. Their research may one day enable soft machines to fully integrate with our bodies to deliver drugs, target tumors, or repair aging or dysfunctional tissue.

Assistant Professor Carson Bruns (left) and Professor Franck Vernerey (right).

Professor Franck Vernerey of the Paul M. Rady Department of Mechanical Engineering and Assistant Professor Carson Bruns of the Paul M. Rady Department of Mechanical Engineering and ATLAS Institute received $477,000 from the National Science Foundation to begin this three-year project in January 2021.

“We are investigating an emerging class of materials known as slide ring polymers that resemble beads on a string,” said Vernerey. “When the network is subjected to a controlled stimulus, the bead-like molecules can slide around, which allows for a new way to actuate the material.”

Naturally occurring molecular machines in the body perform vital cell functions, such as gene replication, protein synthesis or transportation of intracellular cargo. Artificial molecular machines—inspired by those in nature—were recognized by the 2016 Nobel Prize, awarded to early pioneers in this area. Now, Bruns and Vernerey aim to scale up these tiny machines from nanoscale to macroscale using networks.

Instead of one molecule, a network incorporates numerous molecules, linked and working together, as occurs naturally in muscle. The process of starting small and scaling up allows the manmade material to copy how nature organizes molecular machines. To ensure the best results, Vernerey will also create a multiscale model to generate predictions that will help determine exactly how to tweak the molecular structure for the most effective scaling.

“The part that Franck’s group is doing is the first of its kind for these materials,” said Bruns. “It keeps my group from having to go into the lab and make hundreds of networked molecular machines until we find the property that we’re most interested in.”

Likewise, Vernerey said there would be no models without Bruns. “We make for a very cool integration,” said Vernerey.

A schematic showing a slide ring network relaxing (left) and contracting (right). The bead-like molecules slide around, allowing for a new way to actuate the material.

Hydrogels currently are the main available actuator based on molecular interactions, which change shape based on temperature, pH or pulses of electricity. However, these actuators are limited in that they cannot change shape in only one dimension. When a soft material experiences a change in volume instead of just length, its movements are slower, harder to control and a less efficient use of energy.

“Imagine the actuator is a sponge soaked in water, and it takes a long time for the water to leave,” said Vernerey. “The larger the actuator, the longer you have to push out. This means when you want to scale it up, this approach becomes unrealistically slow. The only way to make things fast is to contract without volume change.”

Natural muscle, the inspiration for this project, does this quickly in the body. Each molecular machine pulls on polymer ropes in a microscopic tug-of-war, and the movements collectively result in the muscle shortening to contract and fully extending to relax.

“Another consideration is that our materials can be made to be self-healing, and they are biodegradable, both properties of muscle,” said Bruns.

Bruns said their materials are made of non-toxic, food-grade products. This is significant, because most other actuators—especially those that rely on electricity—are not safe to use inside the body.

“While we hope there will be applications, we are equally interested in better understanding these systems,” said Bruns. To this end, Bruns and Vernerey are also developing interactive lessons in this area for high-school and undergraduate students.

“If you tell a student in high school, I’m just building a polymer, they might not be that excited,” said Vernerey. “But this project has great applications which will help them to be excited about the physics.”

Whether their findings help in tissue engineering or in developing soft micro-robots to mimic and guide cells, among other applications, Bruns and Vernerey said they are excited to be on the frontier of nanotechnology, gaining a better understanding of molecular machines and networks.

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New technology diagnoses sickle cell disease in record time

Anonymous — Thu, 15 Oct 2020 10:25:19 +0000

New technology diagnoses sickle cell disease in record time Anonymous (not verified) Thu, 10/15/2020 - 04:25

Oksana Schuppan

Above: Assistant Professor Xiaoyun Ding in the Biomedical Microfluidics Lab.
Top: Acousto Thermal Shift Assay devices being assembled.

Diseases of the blood, like sickle cell disease, have traditionally taken a full day, tedious lab work and expensive equipment to diagnose, but researchers at the University of ŷ��ڱ��Ƶ Boulder and the University of ŷ��ڱ��Ƶ Anschutz have developed a way to diagnose these conditions with greater sensitivity and precision in only one minute. Their technology is smaller than a quarter and requires only a small droplet of blood to assess protein interactions, dysfunction or mutations.

Assistant Professor Xiaoyun Ding of the Paul M. Rady Department of Mechanical Engineering and Associate Professor Michael Stowell of the Department of Molecular, Cellular and Developmental Biology at ŷ��ڱ��Ƶ Boulder, along with Associate Professor Angelo D’Alessandro of the Departments of Biochemistry and Molecular Genetics and Medicine, Division of Hematology at ŷ��ڱ��Ƶ Anschutz, co-authored a paper about the technology, now featured as the front cover of Small.

This project began when Ding realized that a technology developed in his lab could increase the speed of cell protein analysis performed by Stowell and his research group. As Stowell and D’Alessandro got involved, new applications emerged, including disease diagnosis.

“In Africa, sickle cell disease is the cause of death in 5% of children under 5 years old for lack of early diagnosis,” said D’Alessandro. “This common, life‐threatening genetic disorder is most prevalent in poor regions of the world where newborn screening and diagnosis are rare.”

Sickle cell disease affects hemoglobin, the molecule in red blood cells that delivers oxygen to cells throughout the body. In some areas of the world where malaria is endemic, variants of hemoglobin have evolved that can cause red blood cells to assume a crescent, or sickle, shape.

“Almost all life activities involve proteins,” said Ding. “We thought if we could measure the protein thermal stability change, we could detect these diseases that affect protein stability.”

Proteins have a specific solubility at a specific temperature. When one bonds to another or when the protein is mutated, the solubility changes. By measuring solubility at different temperatures, researchers can tell whether the protein has been mutating.

A completed Acousto Thermal Shift Assay device shown next to a quarter for size comparison. This tiny lab-on-a-chip device can detect protein thermal stability change to diagnose sickle cell disease in one minute.

Before recent developments, Stowell and his group, including researcher Kerri Ball, used Thermal Shift Assays to assess protein stability under varying conditions. Now, with the new technology, an Acousto Thermal Shift Assay, they can do the same but faster and with greater sensitivity.

The ATSA utilizes high-amplitude sound waves, or ultrasound, to heat a protein sample while concentrating the proteins that don’t dissolve. Device components include a channel where the sample is deposited and two electrodes on each side to generate the wave that applies acoustic heating and concentration.

For both a traditional TSA and ATSA, samples are collected and heated from 40 to 70 degrees Celsius. The traditional TSA measures how much of the protein has dissolved at set points over the course of the temperature increase, while the ATSA measures data continuously, recording how much of the protein has dissolved at every fraction of change in degrees Celsius.

“Our method is seven to 34 times more sensitive,” said Ding. “The ATSA can distinguish the sickle cell protein from normal protein, while the traditional TSA method cannot.”

Another benefit of the ATSA is cost reduction in terms of human labor and equipment.

“The traditional methods for thermal profiling require specialized equipment such as calorimeters, polymerase chain reaction machines, and plate readers that require at least some technical expertise to operate,” said Ball. “These instruments are also not very portable, requiring samples to be transported to the instruments for analysis.”

Ball said the ATSA requires only a power source, a microscope and a camera as simple as the one on your smart phone. Because the protein is concentrated, there is also no need to apply a florescent dye as is sometimes required to highlight protein changes in a traditional TSA.

Ding said it is thanks to his collaborators, experts in biochemistry and hematology, that they now know the full impact of the technology.

“This technique is an exciting development, because it represents a new and promising point-of-care platform for a rapid and highly sensitive diagnostic tool of sickle cell disease, and maybe for other hemoglobinopathies such as beta thalassemia too,” said D’Alessandro.

By working with the engineering team, Ball said she and her research group created tools to accomplish their goals in new and better ways.

Diseases of the blood, like sickle cell disease, have traditionally taken a full day, tedious lab work and expensive equipment to diagnose, but researchers across disciplines have developed a way to diagnose these conditions with greater precision in only one minute.

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Dynamic tattoos promise to warn wearers of health threats

Anonymous — Thu, 24 Sep 2020 15:17:03 +0000

Dynamic tattoos promise to warn wearers of health threats Anonymous (not verified) Thu, 09/24/2020 - 09:17

Researchers are developing tattoo inks that do more than make pretty colors. Some can sense chemicals, temperature and UV radiation, setting the stage for tattoos that diagnose health problems.

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Engineers helped lay foundation for campus quantum research efforts, new center

Anonymous — Mon, 31 Aug 2020 21:05:27 +0000

Engineers helped lay foundation for campus quantum research efforts, new center Anonymous (not verified) Mon, 08/31/2020 - 15:05

A new $25 million center to advance quantum science on ŷ��ڱ��Ƶ Boulder’s campus has deep roots in ŷ��ڱ��Ƶ Engineering’s interdisciplinary research efforts.

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Scientists win grant to unravel mystery of how animals track scent

Anonymous — Wed, 12 Aug 2020 06:00:00 +0000

Scientists win grant to unravel mystery of how animals track scent Anonymous (not verified) Wed, 08/12/2020 - 00:00

Seeking to understand how animals follow scent, a team of scientists has won a grant to peer deeply inside the brain as the process takes place.

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Salt solution: Researcher sets out to make desalination more efficient

Anonymous — Fri, 01 Nov 2019 19:22:19 +0000

Salt solution: Researcher sets out to make desalination more efficient Anonymous (not verified) Fri, 11/01/2019 - 13:22

University of ŷ��ڱ��Ƶ Boulder postdoctoral researcher Omkar Supekar of mechanical engineering is working on a technique that could make desalination facilities more efficient by changing the way they detect chemicals that clog up their filters.

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Novel microwave sensor developed at ŷ��ڱ��Ƶ Boulder

Anonymous — Sat, 06 Jul 2019 00:44:03 +0000

Novel microwave sensor developed at ŷ��ڱ��Ƶ Boulder Anonymous (not verified) Fri, 07/05/2019 - 18:44

Vapor cell measuring about half a centimeter in length.

Researchers at ŷ��ڱ��Ƶ Boulder and the National Institute of Standards and Technology are developing sensors based on technologies used in chip-scale atomic clocks and optically pumped magnetometers with sensitivity and accuracy of interest for wireless broadband antenna evaluation technologies. Senior Research Associate Vladislav Gerginov, PhD, from the Department of Physics PREP program who works with mechanical engineering Associate Research Professor Svenja Knappe, recently published a paper entitled, “An Atomic Sensor for Direct Detection of Weak Microwave Signals,” documenting the development of these sensors.

Read the Full Paper

Sensors explored by Gerginov use two experimental techniques:

Optical pumping into an atomic state with decreased spin decoherence
Detection of an off-resonant probe light beam with polarization modulated at the frequency of the microwave field

Both techniques have been successfully executed in room temperature experiments to suppress the spin-exchange decoherence rate, perform quantum noise limited magnetometry, improve the sensitivity of RF magnetometers and entangle a record number of atoms.

Given the sensor’s small size and weight, low power, room-temperature operation, relaxed laser power and linewidth requirements and improved sensitivity rivaling that of sensors based on Rydberg atoms, these sensors present many opportunities for application. The fusion of Gerginov's sensor design with the microfabricated vapor cell technology explored in Knappe's laboratory would lead to the development of miniature sensor arrays for near-field microwave distribution studies.

Due to technology innovation, the demand for use of wireless broadband signals has soared, an area of opportunity for this research group. New types of antennae are being designed with reduced size and increased sensitivity, because spatial resolution, sensitivity and accuracy of measurements based on classical, conductive antennas are becoming insufficient.

The coherent detection of weak microwave signals has important application in emerging communication and radar applications. Additionally, the push for efficient coherent microwave-to-optical conversion and coherent detection of extremely weak and single-photon microwave fields is motivated by applications requiring quantum sensing and microwave qubits. Essential for emerging quantum technologies are coherent microwave-to-optical transducers for linking quantum devices such as microwave qubits and optical memories. Researchers hope to one day perform low-power coherent microwave-to-optical conversion without the need for atomic or cryogenic cooling.

Researchers are developing sensors based on technologies used in chip-scale atomic clocks and optically pumped magnetometers with sensitivity and accuracy able to support wireless broadband antenna technologies.

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Researchers win grant to commercialize miniature microscope

Anonymous — Wed, 03 Jul 2019 14:35:43 +0000

Researchers win grant to commercialize miniature microscope Anonymous (not verified) Wed, 07/03/2019 - 08:35

Victor Bright and a team of ŷ��ڱ��Ƶ Boulder and ŷ��ڱ��Ƶ Anschutz researchers have received a grant to commercialize a miniature microscope that fits on the head of a mouse and can peer deeply inside the living brain.

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Micro/Nanoscale

Mechanical engineering professor asserts that “size matters” when it comes to microscale sensors and machines

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Ding lab aims to improve cancer-fighting immunotherapies with $1.8M grant

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Researchers scale up tiny actuator inspired by muscle

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New technology diagnoses sickle cell disease in record time

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Dynamic tattoos promise to warn wearers of health threats

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Engineers helped lay foundation for campus quantum research efforts, new center

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Scientists win grant to unravel mystery of how animals track scent

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Salt solution: Researcher sets out to make desalination more efficient

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Novel microwave sensor developed at ŷ���ڱ���Ƶ Boulder

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Researchers win grant to commercialize miniature microscope

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Novel microwave sensor developed at ŷ��ڱ��Ƶ Boulder