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Wednesday, January 6th, 2016
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| 4:59a |
Harnessing the energy of small bending motions For many applications such as biomedical, mechanical, or environmental monitoring devices, harnessing the energy of small motions could provide a small but virtually unlimited power supply. While a number of approaches have been attempted, researchers at MIT have now developed a completely new method based on electrochemical principles, which could be capable of harvesting energy from a broader range of natural motions and activities, including walking.
The new system, based on the slight bending of a sandwich of metal and polymer sheets, is described in the journal Nature Communications, in a paper by MIT professor Ju Li, graduate students Sangtae Kim and Soon Ju Choi, and four others.
Most previously designed devices for harnessing small motions have been based on the triboelectric effect (essentially friction, like rubbing a balloon against a wool sweater) or piezoelectrics (crystals that produce a small voltage when bent or compressed). These work well for high-frequency sources of motion such as those produced by the vibrations of machinery. But for typical human-scale motions such as walking or exercising, such systems have limits.
“When you put in an impulse” to such traditional materials, “they respond very well, in microseconds. But this doesn’t match the timescale of most human activities,” says Li, who is the Battelle Energy Alliance Professor in Nuclear Science and Engineering and professor of materials science and engineering. “Also, these devices have high electrical impedance and bending rigidity and can be quite expensive,” he says.
Simple and flexible
By contrast, the new system uses technology similar to that in lithium ion batteries, so it could likely be produced inexpensively at large scale, Li says. In addition, these devices would be inherently flexible, making them more compatible with wearable technology and less likely to break under mechanical stress.
While piezoelectric materials are based on a purely physical process, the new system is electrochemical, like a battery or a fuel cell. It uses two thin sheets of lithium alloys as electrodes, separated by a layer of porous polymer soaked with liquid electrolyte that is efficient at transporting lithium ions between the metal plates. But unlike a rechargeable battery, which takes in electricity, stores it, and then releases it, this system takes in mechanical energy and puts out electricity.
When bent even a slight amount, the layered composite produces a pressure difference that squeezes lithium ions through the polymer (like the reverse osmosis process used in water desalination). It also produces a counteracting voltage and an electrical current in the external circuit between the two electrodes, which can be then used directly to power other devices.
Because it requires only a small amount of bending to produce a voltage, such a device could simply have a tiny weight attached to one end to cause the metal to bend as a result of ordinary movements, when strapped to an arm or leg during everyday activities. Unlike batteries and solar cells, the output from the new system comes in the form of alternating current (AC), with the flow moving first in one direction and then the other as the material bends first one way and then back.
This device converts mechanical to electrical energy; therefore, “it is not limited by the second law of thermodynamics,” Li says, which sets an upper limit on the theoretically possible efficiency. “So in principle, [the efficiency] could be 100 percent,” he says. In this first-generation device developed to demonstrate the electrochemomechanical working principle, he says, “the best we can hope for is about 15 percent” efficiency. But the system could easily be manufactured in any desired size and is amenable to industrial manufacturing process.
Test of time
The test devices maintain their properties through many cycles of bending and unbending, Li reports, with little reduction in performance after 1,500 cycles. “It’s a very stable system,” he says.
Previously, the phenomenon underlying the new device “was considered a parasitic effect in the battery community,” according to Li, and voltage put into the battery could sometimes induce bending. “We do just the opposite,” Li says, putting in the stress and getting a voltage as output. Besides being a potential energy source, he says, this could also be a complementary diagnostic tool in electrochemistry. “It’s a good way to evaluate damage mechanisms in batteries, a way to understand battery materials better,” he says.
In addition to harnessing daily motion to power wearable devices, the new system might also be useful as an actuator with biomedical applications, or used for embedded stress sensors in settings such as roads, bridges, keyboards, or other structures, the researchers suggest.
“This work is very interesting and significant in the sense that it provides a novel approach to converting mechanical energy through an electrochemical route, using a simple design and device structure,” says Wu Wenzhuo, an assistant professor of industrial engineering at Purdue University who was not involved in this work. “More significantly, the output current from the demonstrated device is very large, with a long pulse duration. This is very important for practical applications, since most other mechanical energy harvesting methods suffer from the issues of small current output with short pulse duration.”
Wenzhuo adds that “efficient harvesting of such mechanical energies will help to develop more capable and intelligent wearable devices and human-machine interfaces. … This work presents huge potential in many applications such as flexible electronics, self-powered sensors, wearable devices, human-machine interfaces, robotics, artificial skin, etc.”
The team also included postdoc Kejie Zhao (now assistant professor at Purdue University) and visiting graduate student Giorgia Gobbi , and Hui Yang and Sulin Zhang at Penn State. The work was supported by the National Science Foundation, the MIT MADMEC Contest, the Samsung Scholarship Foundation, and the Kwanjeong Educational Foundation. | | 5:00a |
Tracing a cellular family tree By combining sophisticated RNA sequencing technology with a new device that isolates single cells and their progeny, MIT researchers can now trace detailed family histories for several generations of cells descended from one “ancestor.”
This technique, which can track changes in gene expression as cells differentiate, could be particularly useful for studying how stem cells or immune cells mature. It could also shed light on how cancer develops.
“Existing methods allow for snapshot measurements of single-cell gene expression, which can provide very in-depth information. What this new approach offers is the ability to track cells over multiple generations and put this information in the context of a cell’s lineal history,” says Robert Kimmerling, a graduate student in biological engineering and the lead author of a paper describing the technique in the Jan. 6 issue of Nature Communications.
The paper’s senior authors are Scott Manalis, the Andrew and Erna Viterbi Professor of Biological Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research, and Alex Shalek, the Hermann L.F. von Helmholtz Career Development Assistant Professor of Health Sciences and Technology, an assistant professor of chemistry, and a member of MIT’s Institute for Medical Engineering and Science.
Capturing cell lineage
The new method incorporates a recently developed technology called single-cell RNA-seq, which sequences the messenger RNA from a single cell. These RNAs, known collectively as the transcriptome, reveal which genes are being actively transcribed (that is, copied into messenger RNA instructions for building proteins) inside a cell at a given point in time. This helps scientists understand, for example, what makes a skin cell so different from a heart cell even though the cells share the same DNA.
“Scientists have well established methods for resolving diverse subsets of a population, but one thing that’s not very well worked out is how this diversity is generated. That’s the key question we were targeting: how a single founding cell gives rise to very diverse progeny,” Kimmerling says.
To try to answer that question, the researchers designed a microfluidic device that traps first an individual cell and then all of its descendants. The device has several connected channels, each of which has a trap that can capture a single cell. After the initial cell divides, its daughter cells flow further along the device and get trapped in the next channel. The researchers showed that they can capture up to five generations of cells this way and keep track of their relationships.
To get the cells off the chip, the researchers temporarily reverse the direction of the fluid flowing across the chip, allowing them to remove the cells one at a time to perform single-cell RNA-seq.
In this study, the researchers captured and sequenced immune cells called T cells. These cells are on constant alert in the body, and when they encounter a cell infected with a virus or bacterium, they leap into action, creating two distinct populations — effector T cells, which seek and destroy infected cells, and memory T cells, which retain a memory of the encounter and circulate in the body indefinitely in case of a subsequent encounter.
“A single founding cell can give rise to both effector and memory cell subtypes, but how that diversity is generated isn’t very clear,” Kimmerling says.
The researchers analyzed RNA from recently activated T cells and two subsequent generations. When comparing genes with functions related to T cell activation and differentiation, they found that “sister” cells produced from the same division event are much more similar in their gene expression profiles than two unrelated cells. They also found that “cousin” cells, which have the same “grandmother,” are more similar than unrelated cells, which suggests unique, family-specific transcriptional profiles for single T cells.
The researchers hope that future studies with this device could help to resolve the long-standing debate over how T cells differentiate into effector cells and memory cells. One theory is that the distinction occurs as early as the first T cell division following activation, while a competing theory suggests that the distinction happens later on, as a result of changes in the cells’ microenvironment. To address this question, the researchers believe they would need to analyze the development of T cells taken from a mouse that had been exposed to a foreign pathogen, which would provide a useful model of T cell activation in response to infection.
The new device could also be used to link RNA transcriptome information with other cell traits, the researchers say.
“It opens up possibilities that have never been there before,” Manalis says. “We can further annotate single-cell transcriptome data by applying this strategy to our existing devices for measuring mass, growth rate, density, or deformability.”
“I think this is really beautiful work,” says Dean Felsher, a professor of medicine and pathology at Stanford University School of Medicine. “It builds on what Scott has been doing for a while, which is creating a whole new way of interrogating single-cell measurements. Now he can follow the progeny over multiple generations, which is really hard to do.”
Cellular “age”
In this study, the researchers also discovered that they could use their new technique to learn which genes are expressed at certain points during the cell division cycle. Because they trap each cell and have a record of when it last divided, they can directly link the “age” of each cell to its transcriptome.
They identified a set of about 300 genes that correspond most with time since division (a proxy for cell cycle progression), and found that most of those genes were involved in cell division. Therefore, by measuring the levels of those 300 genes in similar cells, scientists should be able to estimate the ages of those cells. The researchers also found that a leukemia cell line, which proliferates continuously, has a different set of genes that appear to be driving cell division.
“In the future, this approach may be able to provide insight into unique transcriptional regulators of cell cycle progression in various cancer models,” Kimmerling says. | | 5:00a |
Organ-on-a-chip A new technique for programming human stem cells to produce different types of tissue on demand may ultimately allow personalized organs to be grown for transplant patients.
The technique, which also has near-term implications for growing organ-like tissues on a chip, was developed by researchers at MIT and is unveiled in a study published today in the journal Nature Communications.
Growing organs on demand, using stem cells derived from patients themselves, could eliminate the lengthy wait that people in need of a transplant are often forced to endure before one becomes available.
It could also reduce the risk of a patient’s immune system rejecting the transplant, since the tissue would be grown from the patient’s own cells, according to Ron Weiss, professor of biological engineering at MIT, who led the research.
“Imagine that there is a patient with liver complications,” Weiss says. “We could take skin cells from that person and then [convert] them into stem cells, and then genetically program them to make the liver tissue, and transplant that into the patient.”
A rudimentary organ
The researchers developed the new technique while investigating whether they could use stem cells to produce pancreatic beta cells for treating patients with diabetes.
In order to do this, the researchers needed to devise a means to convert stem cells into pancreatic beta cells on demand.
As a first step in this process, they took human induced pluripotent stem (IPS) cells — stem cells generated from adult fibroblast, or skin cells — and converted them into “endoderm,” one of the three primary cell types in a developing organism. Endoderm, mesoderm, and ectoderm make up the three so-called germ layers that contribute to nearly all of the different cell types in the body. “They are the first real step of [cell] differentiation,” Weiss says.
The researchers developed a method to use a type of small molecule called dox to induce the IPS cells to express a protein known as GATA6. This protein can convert IPS cells into endoderm.
Rather than immediately attempting to convert these endoderm cells into pancreatic cells though, the paper’s lead author, Patrick Guye, a former postdoc in Weiss’ lab and currently laboratory head with Sanofi-Aventis in Frankfurt, Germany, then decided to allow the cells to continue growing, to monitor their progress.
After two weeks, the researchers found that the endoderm, and some mesoderm also present in the cell culture, had matured further, to form a liver “bud,” or small, rudimentary liver.
“We observed the development of many cells types found in the fetal liver, including the development of blood vessel-like networks, various mesenchymal precursors, and the formation of early red and white blood cells within our liver-like tissue,” Guye says. “This is especially exciting, as the process looks very similar if not identical to what is happening in the early liver bud in vivo, that is, in our own development.”
What’s more, the researchers discovered that only those IPS cells that had been exposed to more of the genetic programming, and had therefore gone on to produce more GATA6, became liver tissue. Alongside these were IPS cells that did not make much GATA6, which went on to form ectoderm instead, and then further matured to become early telencephalon, or forebrain.
By controlling how much GATA6 the cells expressed, the researchers were able to determine how much liver bud and how much forebrain tissue was generated, Weiss says.
This suggests that the technique could be used to produce not just individual tissue types, but different combinations of tissue, he says.
“The fact that we are able to produce endoderm, mesoderm, and ectoderm gives us great hope that we can take each of these germ layers and hopefully grow any kind of tissue we want,” he says.
Liver-on-a-chip
While it is likely to be some time before the technique can be used to generate transplant organs, it could be used almost immediately to grow different human tissue on which to test new drugs, Weiss says.
Using human stem cell-derived organ tissue to test new treatments could be far more reliable than testing on animals, since different species may react differently to a drug, he says.
The technique could also allow clinicians to carry out patient-specific drug testing. “If you are not sure whether you will have complications from taking a particular drug, then before you take it you could try it out on your own liver-on-a-chip,” Weiss says.
Similarly, the organ-on-a-chip could be used to monitor the interaction between different drugs that people may be taking.
“As people age, some are taking 10, 15, or 20 drugs together, and it’s impossible for the pharmaceutical companies to test all of these combinations for every individual. But we would be able to test that out,” he says. “That is something that can be done now.”
In addition to these therapeutic applications, the technique could allow researchers to gain a better understanding of the development of different types of tissue, such as the liver and neurons.
The paper reveals some intrinsic mechanisms underlying the interactions of stem cells during liver development, and provides a useful model that sheds light on the complex process of embryogenesis, says Bing Song, a professor of tissue engineering at Cardiff University in the UK, who was not involved in the research.
"In my field, which is combining genetically modified stem cells and physical stimulation (electrical and magnetic) to cure spinal cord injuries and degenerative disease, the paper has given me some very useful ideas," he says.
The researchers now hope to investigate whether they can use the technique to grow other organs on demand, such as a pancreas. |
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