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Posts Tagged ‘Graphene’


Artificial throat may give voice to the voiceless

Reporter
Irina Robu, PhD

Flexible sensors have fascinated more and more attention as a fundamental part of anthropomorphic robot research, medical diagnosis and physical health monitoring. The fundamental mechanism of the sensor is based on triboelectric effect inducing electrostatic charges on the surfaces between two different materials. Just like a plate capacitor, current is produced while the size of the parallel capacitor fluctuations caused by the small mechanical disturbances and therefore the output current/voltage is produced.

Chinese scientists combine ultra sensitive motion detectors with thermal sound-emitting technology invented an “artificial throat” that could enable speech in people with damaged or non-functioning vocal cords. Team members from University in Beijing, fabricated a homemade circuit board on which to build out their dual-mode system combining detection and emitting technologies.

Graphene is a wonder material because it is thinnest material in the universe and the strongest ever measured. And graphene is only a one-atom thick layer of graphite and possess a high Young’s modulus as well as superior thermal and electrical conductivities. Graphene-based sensors have attracted much attention in recent years due to their variety of structures, unique sensing performances, room-temperature working conditions, and tremendous application prospects.

The skin like device, wearable artificial graphene throat (WAGT) is as similar as a temporary tattoo, at least as perceived by the wearer. In order to make the device functional and flexible, scientists designed a laser-scribed graphene on a thin sheet of polyvinyl alcohol film. The device is the size of two thumbnails side by side and can use water to attach the film to the skin over the volunteer’s throat and connected to electrodes to a small armband that contained a circuit board, microcomputer, power amplifier and decoder. At the development phase, the system transformed subtle throat movements into simple sounds like “OK” and “No.” During the trial of the device, volunteers imitated throat motions of speech and the device converted these movements into single-syllable words.

It is believed that this device, would be able to train mute people to generate signals with their throats and the device would translate signals into speech.

SOURCE
https://www.aiin.healthcare/topics/robotics/artificial-throat-may-give-voice-voiceless?utm_source=newsletter

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Black hole nanoscience?


Black hole nanoscience?

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

A black hole on a chip made of a metal that behaves like water

First model system of relativistic hydrodynamics in a metal; energy- and sensing-applications also seen
February 12, 2016

http://www.kurzweilai.net/a-black-hole-on-a-chip-made-of-a-metal-that-behaves-like-water

 

In a new paper published in Science, researchers at the Harvard and Raytheon BBN Technology have observed, for the first time, electrons in a metal behaving like a fluid (credit: Peter Allen/Harvard SEAS)

A radical discovery by researchers at Harvard and Raytheon BBN Technology about graphene’s hidden properties could lead to a model system to explore exotic phenomena like black holes and high-energy plasmas, as well as novel thermoelectric devices.

In a paper published Feb. 11 in Science, the researchers document their discovery of electrons in graphene behaving like a fluid. To make this observation, the team improved methods to create ultra-clean graphene* and developed a new way to measure its thermal conductivity.

A black hole on a chip

In ordinary 3D metals, electrons hardly interact with each other. But graphene’s two-dimensional, honeycomb structure acts like an electron superhighway in which all the particles have to travel in the same lane. The electrons in this ultra-clean graphene act like massless relativistic objects, some with positive charge and some with negative charge.

They move at incredible speed — 1/300 of the speed of light — and have been predicted to collide with each other ten trillion times a second at room temperature.  These intense interactions between charge particles have never been observed in an ordinary metal before.

Most of our world is described by classical physics. But very small things, like electrons, are described by quantum mechanics while very large and very fast things, like galaxies, are described by relativistic physics, pioneered by Albert Einstein.

Combining these different sets of laws of physics is notoriously difficult, but there are extreme examples where they overlap. High-energy systems like supernovas and black holes can be described by linking classical theories of hydrodynamics with Einstein’s theories of relativity.

A quantum ‘Dirac’ fluid metal

But since we can’t run an experiment on a black hole (yet), enter graphene.

When the strongly interacting particles in graphene were driven by an electric field, they behaved not like individual particles but like a fluid that could be described by hydrodynamics.

“Physics we discovered by studying black holes and string theory, we’re seeing in graphene,” said Andrew Lucas, co-author and graduate student with Subir Sachdev, the Herchel Smith Professor of Physics at Harvard. “This is the first model system of relativistic hydrodynamics in a metal.”

Industrial implications

A small chip of graphene could also be used to model the fluid-like behavior of other high-energy systems.

To observe the hydrodynamic system, the team turned to noise. At finite temperature, the electrons move about randomly:  the higher the temperature, the noisier the electrons. By measuring the temperature of the electrons to three decimal points, the team was able to precisely measure the thermal conductivity of the electrons.

“This work provides a new way to control the rate of heat transduction in graphene’s electron system, and as such will be key for energy and sensing-related applications,” said Leonid Levitov, professor of physics at MIT.

“Converting thermal energy into electric currents and vice versa is notoriously hard with ordinary materials,” said Lucas. “But in principle, with a clean sample of graphene there may be no limit to how good a device you could make.”

The research was led by Philip Kim, professor of physics and applied physics at The Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS).

* The team created an ultra-clean sample by sandwiching the one-atom thick graphene sheet between tens of layers of an electrically insulating perfect transparent crystal with a similar atomic structure of graphene.

“If you have a material that’s one atom thick, it’s going to be really affected by its environment,” said Jesse Crossno, a graduate student in the Kim Lab and first author of the paper. “If the graphene is on top of something that’s rough and disordered, it’s going to interfere with how the electrons move. It’s really important to create graphene with no interference from its environment.”

Next, the team set up a kind of thermal soup of positively charged and negatively charged particles on the surface of the graphene, and observed how those particles flowed as thermal and electric currents.

 

https://youtu.be/lvi3nG2Mwsw

Harvard John A. Paulson School of Engineering and Applied Sciences | How to Make Graphene

 

Abstract of Observation of the Dirac fluid and the breakdown of the Wiedemann-Franz law in graphene

Interactions between particles in quantum many-body systems can lead to collective behavior described by hydrodynamics. One such system is the electron-hole plasma in graphene near the charge neutrality point, which can form a strongly coupled Dirac fluid. This charge neutral plasma of quasi-relativistic fermions is expected to exhibit a substantial enhancement of the thermal conductivity, thanks to decoupling of charge and heat currents within hydrodynamics. Employing high sensitivity Johnson noise thermometry, we report an order of magnitude increase in the thermal conductivity and the breakdown of the Wiedemann-Franz law in the thermally populated charge neutral plasma in graphene. This result is a signature of the Dirac fluid, and constitutes direct evidence of collective motion in a quantum electronic fluid.

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Advanced Nanospectroscopy

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

Graphene Enables Nanoelectromechanical Systems Integration

http://www.photonics.com/Article.aspx?AID=58224&refer=Spectroscopy&utm_source=Spectroscopy_2016_02_03

BARCELONA, Spain, Jan. 21, 2016 — Combining nanoelectromechanical (NEMS) systems with on-chip optics holds promise as a method to actively control light at the nanoscale, and now a hybrid system has overcome the challenges of integrating such nanoscale devices with optical fields thanks to the material graphene.

Researchers from the Institute of Photonic Sciences (ICFO) have demonstrated an on-chip graphene NEMS suspended a few tens of nanometers above nitrogen-vacancy centres (NVCs), which are stable single-photon emitters embedded in nanodiamonds. The work confirms that graphene is an ideal platform for both nanophotonics and nanomechanics, the researchers said.

Due to its electromechanical properties, graphene NEMS can be actuated and deflected electrostatically over a few tens of nanometers with modest voltages applied to a gate electrode, the researchers found. The graphene motion can thus be used to modulate the light emission by the NVC, while the emitted field can be used as a universal probe of the graphene position. The optomechanical coupling between the graphene displacement and the NVC emission is based on near-field, dipole-dipole interaction.

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http://www.photonics.com/images/Web/Articles/2016/1/21/PIC_ICFO.jpg

False color scanning electronic micrograph of a hybrid graphene-nitrogen-vacancy nearfield nano-optomechanical system. Courtesy of ICFO.

The researchers observed that the coupling strength increased strongly for shorter distances and was enhanced because of graphene’s 2D character and linear dispersion. These achievements hold promise for selective control of emitter arrays on-chip, optical spectroscopy of individual nano-objects, and integrated optomechanical information processing. The ICFO team also said the hybrid device could advance quantum optomechanics.

The research was published in Nature Communications (doi: 10.1038/ncomms10218).

Electromechanical control of nitrogen-vacancy defect emission using graphene NEMS

Antoine Reserbat-PlanteyKevin G. SchädlerLouis GaudreauGabriele NavickaiteJohannes Güttinger, et al.

Nature Communications 2016; 7(10218)      http://dx.doi.org:/10.1038/ncomms10218

Despite recent progress in nano-optomechanics, active control of optical fields at the nanoscale has not been achieved with an on-chip nano-electromechanical system (NEMS) thus far. Here we present a new type of hybrid system, consisting of an on-chip graphene NEMS suspended a few tens of nanometres above nitrogen-vacancy centres (NVCs), which are stable single-photon emitters embedded in nanodiamonds. Electromechanical control of the photons emitted by the NVC is provided by electrostatic tuning of the graphene NEMS position, which is transduced to a modulation of NVC emission intensity. The optomechanical coupling between the graphene displacement and the NVC emission is based on near-field dipole–dipole interaction. This class of optomechanical coupling increases strongly for smaller distances, making it suitable for nanoscale devices. These achievements hold promise for selective control of emitter arrays on-chip, optical spectroscopy of individual nano-objects, integrated optomechanical information processing and open new avenues towards quantum optomechanics.

 

Graphene is ideal substrate for brain electrodes, researchers find

February 1, 2016  http://www.kurzweilai.net/graphene-is-ideal-substrate-for-brain-electrodes-researchers-find

This illustration portrays neurons interfaced with a sheet of graphene molecules in the background (credit: Graphene Flagship)

An international study headed by the European Graphene Flagship research consortium has found that graphene is a promising material for use in electrodes that interface with neurons, based on its excellent conductivity, flexibility for molding into complex shapes, biocompatibility, and stability within the body.

The graphene-based substrates they studied* promise to overcome problems with “glial scar” tissue formation (caused by electrode-based brain trauma and long-term inflammation). To avoid that, current electrodes based on tungsten or silicon use a protective coating on electrodes, which reduces charge transfer. Current electrodes are also rigid (resulting in tissue detachment and preventing neurons from moving) and generate electrical noise, with partial or complete loss of signal over time, the researchers note in a paper published recently in the journal ACS Nano.

Electrodes are used as neural biosensors and for prosthetic applications — such as deep-brain intracranial electrodes used to control motor disorders (mainly epilepsy or Parkinson’s) and for brain-computer interfaces (BCIs), used to recover sensory functions or control robotic arms for paralyzed patients. These applications require an interface with long-term, minimal interference.

Interfacing graphene to neurons directly

Scanning electron microscope image of rat hippocampal neurons grown in the lab on a graphene-based substrate, showing normal morphology characterized by well-defined round neural soma, extended neurite arborization (branching), and cell density similar to control substrates (credit: A. Fabbro et al./ACS Nano)

“For the first time, we interfaced graphene to neurons directly, without any peptide-coating,” explained lead neuroscientist Prof. Laura Ballerini of the International School for Advanced Studies (SISSA/ISAS) and the University of Trieste.

Using electron microscopy and immunofluorescence, the researchers found that the neurons remained healthy, transmitting normal electric impulses and, importantly, no adverse glial reaction, which leads to damaging scar tissue, was seen.

As a next step, Ballerini says the team plans to investigate how different forms of graphene, from multiple layers to monolayers, are able to affect neurons,  and “whether tuning the graphene material properties might alter the synapses and neuronal excitability in new and unique ways.”

Prof. Andrea C. Ferrari, Director of the Cambridge Graphene Centre and Chair of the Graphene Flagship Executive Board, said the Flagship will “support biomedical research and development based on graphene technology with a new work package and a significant cash investment from 2016.”

The interdisciplinary collaboration also included the University Castilla-La Mancha and the Cambridge Graphene Centre.

* The study used two methods of creating graphene-based substrates (GBSs).  Liquid phase exfoliation (LPE) — peeling off graphene from graphite — can be performed without the potentially hazardous chemical treatments involved in graphene oxide production, is scalable, and operates at room temperature, with high yield. LPE dispersions can also be easily deposited on target substrates by drop-casting, filtration, or printing. Ball milling (BM), with the help of melamine (which forms large hydrogen-bond domains, unlike LPE), can be performed in a solid environment. “Our data indicate that both GBSs are promising for next-generation bioelectronic systems, to be used as brain interfaces,” the paper concludes.

 

 

 

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Graphene Interaction with Neurons

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

Graphene Shown to Safely Interact with Neurons in the Brain

University of Cambridge

(Source: University of Cambridge)

http://www.biosciencetechnology.com/sites/biosciencetechnology.com/files/bt1601_cambridge_graphene.png

 

Researchers have successfully demonstrated how it is possible to interface graphene – a two-dimensional form of carbon – with neurons, or nerve cells, while maintaining the integrity of these vital cells. The work may be used to build graphene-based electrodes that can safely be implanted in the brain, offering promise for the restoration of sensory functions for amputee or paralyzed patients, or for individuals with motor disorders such as epilepsy or Parkinson’s disease.

The research, published in the journal ACS Nano, was an interdisciplinary collaboration coordinated by the University of Trieste in Italy and the Cambridge Graphene Centre.

Previously, other groups had shown that it is possible to use treated graphene to interact with neurons. However the signal to noise ratio from this interface was very low. By developing methods of working with untreated graphene, the researchers retained the material’s electrical conductivity, making it a significantly better electrode.

“For the first time we interfaced graphene to neurons directly,” said Professor Laura Ballerini of the University of Trieste in Italy. “We then tested the ability of neurons to generate electrical signals known to represent brain activities, and found that the neurons retained their neuronal signaling properties unaltered. This is the first functional study of neuronal synaptic activity using uncoated graphene based materials.”

Our understanding of the brain has increased to such a degree that by interfacing directly between the brain and the outside world we can now harness and control some of its functions. For instance, by measuring the brain’s electrical impulses, sensory functions can be recovered. This can be used to control robotic arms for amputee patients or any number of basic processes for paralyzed patients – from speech to movement of objects in the world around them. Alternatively, by interfering with these electrical impulses, motor disorders (such as epilepsy or Parkinson’s) can start to be controlled.

Scientists have made this possible by developing electrodes that can be placed deep within the brain. These electrodes connect directly to neurons and transmit their electrical signals away from the body, allowing their meaning to be decoded.

However, the interface between neurons and electrodes has often been problematic: not only do the electrodes need to be highly sensitive to electrical impulses, but they need to be stable in the body without altering the tissue they measure.

Too often the modern electrodes used for this interface (based on tungsten or silicon) suffer from partial or complete loss of signal over time. This is often caused by the formation of scar tissue from the electrode insertion, which prevents the electrode from moving with the natural movements of the brain due to its rigid nature.

Graphene has been shown to be a promising material to solve these problems, because of its excellent conductivity, flexibility, biocompatibility and stability within the body.

Based on experiments conducted in rat brain cell cultures, the researchers found that untreated graphene electrodes interfaced well with neurons. By studying the neurons with electron microscopy and immunofluorescence the researchers found that they remained healthy, transmitting normal electric impulses and, importantly, none of the adverse reactions which lead to the damaging scar tissue were seen.

According to the researchers, this is the first step towards using pristine graphene-based materials as an electrode for a neuro-interface. In future, the researchers will investigate how different forms of graphene, from multiple layers to monolayers, are able to affect neurons, and whether tuning the material properties of graphene might alter the synapses and neuronal excitability in new and unique ways. “Hopefully this will pave the way for better deep brain implants to both harness and control the brain, with higher sensitivity and fewer unwanted side effects,” said Ballerini.

“We are currently involved in frontline research in graphene technology towards biomedical applications,” said Professor Maurizio Prato from the University of Trieste. “In this scenario, the development and translation in neurology of graphene-based high-performance biodevices requires the exploration of the interactions between graphene nano- and micro-sheets with the sophisticated signalling machinery of nerve cells. Our work is only a first step in that direction.”

“These initial results show how we are just at the tip of the iceberg when it comes to the potential of graphene and related materials in bio-applications and medicine,” said Professor Andrea Ferrari, Director of the Cambridge Graphene Centre. “The expertise developed at the Cambridge Graphene Centre allows us to produce large quantities of pristine material in solution, and this study proves the compatibility of our process with neuro-interfaces.”

The research was funded by the Graphene Flagship, a European initiative which promotes a collaborative approach to research with an aim of helping to translate graphene out of the academic laboratory, through local industry and into society.

Source: University of Cambridge

 

Remembering to Remember Supported by Two Distinct Brain Processes

http://www.biosciencetechnology.com/news/2013/08/remembering-remember-supported-two-distinct-brain-processes

To investigate how prospective memory is processed in the brain, psychological scientist Mark McDaniel of Washington University in St. Louis and colleagues had participants lie in an fMRI scanner and asked them to press one of two buttons to indicate whether a word that popped up on a screen was a member of a designated category.  In addition to this ongoing activity, participants were asked to try to remember to press a third button whenever a special target popped up. The task was designed to tap into participants’ prospective memory, or their ability to remember to take certain actions in response to specific future events.

When McDaniel and colleagues analyzed the fMRI data, they observed that two distinct brain activation patterns emerged when participants made the correct button press for a special target.

When the special target was not relevant to the ongoing activity—such as a syllable like “tor”—participants seemed to rely on top-down brain processes supported by the prefrontal cortex. In order to answer correctly when the special syllable flashed up on the screen, the participants had to sustain their attention and monitor for the special syllable throughout the entire task. In the grocery bag scenario, this would be like remembering to bring the grocery bags by constantly reminding yourself that you can’t forget them.

When the special target was integral to the ongoing activity—such as a whole word, like “table”—participants recruited a different set of brain regions, and they didn’t show sustained activation in these regions. The findings suggest that remembering what to do when the special target was a whole word didn’t require the same type of top-down monitoring. Instead, the target word seemed to act as an environmental cue that prompted participants to make the appropriate response—like reminding yourself to bring the grocery bags by leaving them near the front door.

“These findings suggest that people could make use of several different strategies to accomplish prospective memory tasks,” says McDaniel.

McDaniel and colleagues are continuing their research on prospective memory, examining how this phenomenon might change with age.

Co-authors on this research include Pamela LaMontagne, Michael Scullin, Todd Braver of Washington University in St. Louis; and Stefanie Beck of Technische Universität Dresden.

This research was funded by the National Institute on Aging, the Washington University Institute of Clinical and Translation Sciences, the National Center for Advancing Translational Sciences, and the German Science Foundation.

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Augmentation of the ONTOLOGY of the 3D Printing Research

Curator: Larry H. Bernstein, MD, FCAP

Encore: Research Allows for 3D Printed Augmentation of Everyday Objects

BY BRIAN KRASSENSTEIN

http://3dprint.com/87595/encore-3d-print-augment/

If you have a 3D printer then you are likely overwhelmed by the sheer number of possible objects you can find online to print out. At the same time, the technology is somewhat limited, unless you have professional CAD skills or are incredibly creative. What, for instance, would you do if you wanted to take an everyday item such as a hot glue gun and print an attached stand for it, or turn your child’s favorite action figure into a magnet?

Four researchers at Carnegie Mellon University, Xiang ‘Anthony’ Chen, Stelian Coros, Jennifer Mankoff and Scott E. Hudson, believe that they can change this via a new WebGL-based tool under development called Encore.

Funded by the National Science Foundation under grant NSF IIS 1217929, Encore is a multifaceted tool which enables three different techniques to augment already existing objects. The researchers call these three techniques Print-Over, Print-to-Affix and Print-Through, all of which allow for the adherence of newly 3D printed attachments to other objects. Before we get into what each of these three techniques involves, one first should understand the computational pipeline involved in designing these attachments.

First a user is required to design a basic attachment, or perhaps use a design that they’d like to iterate upon. Once they have a basic model of their desired attachment the Encore system will geometrically analyze the model along with a 3D scan of a target object, that the attachment will adhere to, in order to determine its printability while also deciding if it will be durable enough and usable once attached to the target object. Next comes the interactive exploration phase, where the tool will visualize and explore various areas where the attachment can be affixed to the target object. The tool will also adjust the design of the attachment, if required, to better fit the target object. Once this is all settled, it’s now time for Encore to generate a model which not only will include the attachment itself, but also any connecting structures and even supports to hold the target item or attachment in place. Below you will find the three techniques that the Encore tool can use to attach 3D printed items to a target object:

Print-Over
This technique, in my opinion, is one of the coolest, as it allows for the printing of an attachment directly on a given object. Once Encore establishes the parameters required and sizes up the model to fit the target object, it will automatically tell the printer to print supports to hold the target item in place. Once the target item is in place, Encore will then tell the printer to begin printing the attachment in a particular spot on the target item, based on its geometric analysis of that object.

“It is also important to ensure that the existing object will not impede the motion of the print head while the attachment is being printed,” warn the researchers.

An example used by the researchers for this technique was a magnet holder which they directly attached to a teddy bear figurine. They also printed an LED light onto a 9V battery by first placing a small amount of glue on the battery prior to beginning to print on top.

Print-to-Affix
This approach is similar to the Print-Over technique, only that instead of printing an attachment directly onto the target object, Encore will analyze the geometry of the target object prior to printing in order to create an attachment which will fit perfectly on that object via glue, straps (zip-ties) or even snaps. Once the attachment is printed the user can then use hot-glue or another adhesive or attachment mechanism to affix the printed object onto the target.

Print-Through
This technique is perfect for items which you don’t want to physically attach, but instead can connect to an object. For instance a tag on the loop of a pair of scissors or a charm onto a bracelet. This process requires that the printer be paused while a user manually places the target object within the print field.

“Print-through has aesthetic qualities that distinguish it from print-to-affix and print-over – it typically creates a loose but permanent connection between two objects,” explained the researchers.

While the new Encore tool is still under development as researchers improve upon its analytical capabilities, it certainly seems to show promise to those of us wishing to do more than just fabricate new items. In fact, the researchers were able to show that via all three techniques they could save a substantial amount of time and material over printing an object in one single piece. As an example, they used Slic3r to estimate the print time and total material required for printing a typical Utah teapot with a torus-shaped handle, as well as just printing the handle onto an already fabricated Utah teapot. Their estimate showed that the time of fabricating the item could be cut by more than 80% and material use reduced by as much as 85% by using their techniques and the Encore tool.

There are many variables going into the tool’s decision making algorithms, such as determining where to place attachments for the best balance when holding an object, what placement of an attachment will result in the best adhesion, etc. More research is still required as the team continues to develop the tool, as well as new techniques to attach multiple parts to one object, but it certainly seems like something which could have a sizable impact on the industry in general. Let us know your thoughts on the Encore tool in the Augmenting 3D Prints forum thread on 3DPB.com.

The Limits of 3D Printing

Matthias Holweg

Harvard Business Review Feb 2015   https://hbr.org/2015/06/the-limits-of-3d-printing

Contrary to what some say, 3D printing is not going to revolutionize the manufacturing sector, rendering traditional factories obsolete. The simple fact of the matter is the economics of 3D printing now and for the foreseeable future make it an unfeasible way to produce the vast majority of parts manufactured today. So instead of looking at it as a substitute for existing manufacturing, we should look to new areas where it can exploit its unique capabilities to complement traditional manufacturing processes.

Additive manufacturing, or “3D printing” as it is commonly known, has understandably captured the popular imagination: New materials that can be “printed” are announced virtually every day, and the most recent generation of printers can even print several materials at the same time, opening up new opportunities. Exciting applications have already been demonstrated across all sectors — from aerospace and medical applications to biotechnology and food production.

Some predict that a day is coming when we’ll be able to make any part at the push of a button at a local printer, which might even render the global supply lines that dominate today’s world of manufacturing a thing of the past. Unfortunately, this vision does not stack up to economic reality. Early findings from a research project being conducted by the Additive Manufacturing and 3D Printing Research Group at the University of Nottingham and Saïd Business School at the University of Oxford show that there are both significant scale and learning effects inherent in the 3D printing process. (The project, in which I am a principal investigator, is focusing on industrial selective laser sintering (or more accurately, melting) processes and not fused deposition modelling or stereolithography processes that are more suited to rapid prototyping and home applications.)

Furthermore, the pre- and post-printing cost amount to a significant proportion of total cost per printed part. So even when the cost for printers materials come down, the labor-cost penalty will remain.

3D printing simply works best in areas where customization is key — from printing hearing aids and dental implants to printing a miniature of the happy couple for their wedding cake. Using a combination of 3D scanning and printing, implants can be customized to specific anatomic circumstances in a way that was simply not feasible beforehand. However, we also know that 99% of all manufactured parts are standard and do not require customization. In these cases, 3D printing has to compete with scale-driven manufacturing processes and rather efficient logistics operations. A good example is the wrench  that NASA printed on the International Space Station last year. The cost of shipping it to the space station would have been at least $400 (assuming the unpackaged weight of 18 grams per wrench and using the most recent cost data given by NASA for transporting goods into lower-earth orbit); in comparison, shipping it from China to the United States would only cost $0.002 per unit. Thus, while it makes a lot of sense to print the wrench on the space station, printing it for local consumption in the United States wouldn’t.

The simple fact is that when customization isn’t important, 3D printing is not competitive. For one, printing costs per part are highly sensitive to the utilization of the “build room,” the three-dimensional area inside the 3D printer where the laser fuses the metal or plastic powder. Therefore, contract manufacturers that perform 3D printing  such as Shapeways generally wait to fill a batch that uses the entire build room. Printing just one part raises unit cost considerably; so economies of scale do matter. Interestingly, the economic case for the most-cited standard part in 3D volume production today, the GE fuel nozzle for the CFM LEAP engine, is it is lighter and more fuel efficient, not a lower manufacturing cost per se.

A second point often overlooked is that the labor cost that remains. Counter to common perception, 3D printing does not happen “at the touch of a button”; it involves considerable pre- and post-processing, which incur non-trivial labor costs. The starting point for any 3D printing process is a 3D file that can be “printed.” Just having an electronic CAD drawing is not sufficient; currently, there is no way to automatically convert the CAD drawing into a 3D file.

Creating printable files involves two steps: creating a three-dimensional volume model that can be printed, and “slicing” that volume model in the best possible way to avoid material wastage and prevent printing errors. Both steps require tacit knowledge. Following the printing, the parts produced have to be recovered, cleaned, washed (or sanded and polished, in the case of metal prints), and inspected. This, in turn, means that using 3D printing for the aftermarket services — an application where it makes a lot of sense — requires making a significant upfront investment in generating the printable files of the spare parts that would likely be needed. This investment would have to outweigh the cost of keeping a lifetime supply of spare parts in inventory, which is a tough call for small bolts, brackets, and connectors that make up the bulk of aftermarket demand.

So while I, like many others, have fallen in love with the notion of the “ultimate lean supply chain” of having 3D printers at every other corner table to print single parts just in time where they are needed, I am afraid that this vision does not stack up against reality. 3D printing technology undoubtedly has great potential. However, it is unlikely to replace traditional manufacturing. Instead, we should see it as a complement, a new tool in the box, and exploit its unique capabilities — both in making existing products better as well as being able to manufacture entirely new ones that we previously could not make.

Medical implants and printable body parts to drive 3D printer growth

With 3D bio-printing in the pipeline, dental and medical applications could be worth $6bn by 2025

http://www.theguardian.com/business/2014/aug/24/medical-implants-drive-3d-printer-growth

False teeth, hip joints and replacement knees – and potentially printable skin and organs – will drive growth in the burgeoning market for 3D printers over the next decade, according to new research.

A report suggests that dentistry and medicine will increasingly harness one of the 21st century’s most exciting technological breakthroughs.

The technology is better known to British households for its ability to replace broken crockery or produce awkward figurine “selfies.”

But a report by Cambridge-based market research firm IDTechEx says ceramic jaw or teeth implants and metal hip replacements will become increasingly common 3D fare.

The parts are created by nozzles laying down fine sedimentary layers of material that build a product indistinguishable from an item that has rolled off a factory conveyor belt.

The dental and medical market for 3D printers is expected to expand by 365% to $867m (£523m) by 2025, according to IDTechEx analysts, even before bio-printing technology is taken into account. If bio-printing becomes suitable for commercial use – which scientists hope will allow the printing of pieces of skin, liver or kidney using live cells – analysts estimate the medical market could reach a value of $6bn or more within 10 years.

While printing of complete organs for transplants may be decades away, the use of pieces of tissue for laboratory toxicology tests for cosmetics or drugs could be ready within five years, helping the medical market for 3D printers overtake all other sectors.

Dr Jon Harrop, a director of IDTechEx, said: “Bio printing is a bit unsure as it doesn’t exist commercially at the moment but all the medical professionals we interviewed thought it was highly likely to be commercial within 10 years.”

In the US, dental labs have invested in technology that can scan a patient’s teeth so new teeth can be produced by pressing the print button.

Harrop said there are a number of stumbling blocks in the way of the commercial application of bio printing, but even in the past year, scientists have been able to extend the life of a piece of skin tissue created in the lab from just a few hours to 40 days, taking it closer to the three months required for toxicology tests.

At present, 3D printers are most widely used in the automotive industry where they help produce prototypes for new cars or car parts. The next biggest market is aerospace, where manufacturers are using the technology to make lighter versions of complex parts for aeroplanes.

Already, 3D printers have been used by the medical industry to create a jaw, a pelvis and several customised hip replacements from metal. This year, surgeons in Newcastle upon Tyne created a titanium pelvis for a man who lost half his original one to a rare bone cancer, while in May doctors in Southampton completed Britain’s first hip replacement made using a 3D printer. Professor Richard Oreffo at the University of Southampton, who helped develop the hip replacement technique, said at the time: “The 3D printing of the implant in titanium, from CT scans of the patient and stem cell graft, is cutting edge and offers the possibility of improved outcomes for patients.”

Dentists have been using 3D printers to create exact replicas of jaws or teeth in order to aid complex procedures for a few years, but increasingly they are creating implants made of durable plastic or medical ceramics.

The Future of 3D Printing

By Stephen F. DeAngelis

http://www.enterrasolutions.com/2013/03/the-future-of-3d-printing.html

In his most recent State of the Union address, President Barack Obama stated, “Last year, we created our first manufacturing innovation institute in Youngstown, Ohio. A once-shuttered warehouse is now a state-of-the art lab where new workers are mastering the 3D printing that has the potential to revolutionize the way we make almost everything. There’s no reason this can’t happen in other towns. So tonight, I’m announcing the launch of three more of these manufacturing hubs, where businesses will partner with the Department of Defense and Energy to turn regions left behind by globalization into global centers of high-tech jobs. And I ask this Congress to help create a network of 15 of these hubs and guarantee that the next revolution in manufacturing is made right here in America.” [“Remarks by the President in the State of the Union Address,” White House, 12 February 2013]

Official White House Photo by Chuck Kennedy (not shown)

Clearly, the President believes that 3D printing marks a new era in manufacturing that could change the entire business landscape. Kinaxis analyst Andrew Bell agrees that “change is inevitable.” “The question that we need to answer,” he writes, “is how will it change?” [“What Could 3D Printing Mean for the Supply Chain? The 21st Century Supply Chain, 9 January 2013] Bell offers a few thoughts on the subject; he writes:

“One thing is for sure, the supply chain isn’t going away. As usual, it will likely just get more complicated. Here are some of the areas that I propose will influence the supply chain as 3D printing becomes more and more mainstream, and I’m sure there are many more.

  • Local Manufacturing – More things will be made closer to their final destination. This will have definite impact on the logistics industry, and will change the way business try and schedule their operations.
  • Customizability – It will be easier, faster, and more efficient for companies to provide made-to-order products to their end users.
  • Distribution of raw materials – There will need to be a dramatic shift in the way raw materials are distributed since these printers will require raw materials in order to produce the final product.
  • New replacement parts model – Business will be able to provide replacement parts as required instead of trying to predict the need and manufacture the stock well in advance (as they do today)
  • Blurred boundaries within businesses – A closer integration of the various departments of an organization will be mandatory. A siloed manufacturing department will no longer allow for a competitive business.

“My predictions may be right, or they may be wrong, but one thing I think all will agree on is that 3D printing will make the supply chain more complex and more difficult to manage.”

Jim Stockton notes that 3D printing (or additive manufacturing) has been around since the 1980s. It has only broken into the mainstream because of recent breakthroughs that now have everyone talking. [“Top Innovations in the World of 3D Printing,” BestDesignTuts, 12 February 2013] He writes:

“Some products produced with this technology that might already be a part of your daily life include shoes, jewellery, clothing accessories, and educational products. The field of engineering is also benefitting from the development of 3D printing, in terms of boosting geographic information systems, aerospace engineering, engineering projects, and construction processes. Furthermore, humans are already benefitting in the field of healthcare with dental and medical instruments and products being formulated with 3D printing. The automotive industry is able to make more reliable products at a quicker speed, and the industrial design and architecture fields are able to develop new products that were inconceivable only a decade ago.”

What is really exciting people, however, is not so much what is currently being manufactured but the potential of what could be manufactured using 3D printers. Stockton writes:

“Engineers and scientists around the world are looking forward to the near future, in which printers will be able to create equipment, tools and devices via open-source models. This kind of advancement will drastically change the ways in which research and practical medicine are performed. Chemists are even attempting to build chemical compounds using 3D printers, and scientists have already started to replicate fossils and other ancient materials to better understand their compositions and functions. Architects wonder if in the future, buildings themselves can be printed from the ground up. The future of 3D printing is very bright – both in small-scale products for individual users and for large-scale projects, such as printing meters of building materials in the course of an hour and making intricate parts of automobiles and planes.”

http://www.enterrasolutions.com/media/images/2013/03/6a00d8341c4ebd53ef017c36e043b0970b-600wi.jpg

Vivek Srinivasan and Jarrod Bassan offer ten trends that will likely define the direction that will be taken by additive manufacturing in the years ahead. [“Manufacturing The Future: 10 Trends To Come In 3D Printing,” Forbes, 7 December 2012] They are:

  1. 3D printing becomes industrial strength. Once reserved for prototypes and toys, 3D printing will become industrial strength. You will take a flight on an airliner that includes 3D-printed components, making it lighter and more fuel efficient. In fact, there are aircrafts that already contain some 3D-printed components. The technology will also start to be adopted for the direct manufacture of specialist components in industries like defense and automotive. Overall, the number of 3D printed parts in planes, cars and even appliances will increase without you knowing.
  2. 3D printing starts saving lives. 3D-printed medical implants will improve the quality of life of someone close to you. Because 3D printing allows products to be custom-matched to an exact body shape, it is being used today for making better titanium bone implants, prosthetic limbs and orthodontic devices. Experiments in printing soft tissue are underway, and may soon allow printed veins and arteries to be used in operations. Today’s research into medical applications of 3D printing covers nano-medicine, pharmaceuticals and even printing of organs. Taken to the extreme, 3D printing could one day enable custom medicines and reduce if not eliminate the organ donor shortage.
  3. Customization becomes the norm. You will buy a product, customized to your exact specifications, which is 3D-printed and delivered to your doorstep. Innovative companies will use 3D printing technologies to give themselves a competitive advantage by offering customization at the same price as their competitor’s standard products. At first this may range from novelty items like custom smartphone cases or ergonomic improvements to standard tools, but it will rapidly expand to new markets. The leaders will adjust their sales, distribution and marketing channels to take advantage of their capability to provide customization direct to the customer. Customization will also play a big role in healthcare devices such as 3D-printed hearing aids and artificial limbs.
  4. Product innovation is faster. Everything from new car models to better home appliances will be designed more rapidly, bringing innovation to you faster. Because rapid prototyping using 3D printers reduces the time to turn a concept into a production-ready design, it allows designers to focus on the function of products. Although the use of 3D printing for rapid prototyping is not new, the rapidly decreasing cost, improved design software and increasing range of printable materials means designers will have more access to printers, allowing them to innovate faster by 3D printing an object early in the design phase, modifying it, re-printing it, and so on. The result will be better products, designed faster.
  5. New companies develop innovative business models built on 3D printing. You will invest in a 3D printing company’s IPO. Start-up companies will flourish as a generation of innovators, hackers and “makers” take advantage of the capabilities of 3D printing to create new products or deliver services to the burgeoning 3D printer market. Some enterprises will fail, and there may be a boom-bust cycle, but 3D printing will spawn new and creative business models.
  6. 3D print shops open at the mall. 3D print shops will begin to appear, at first servicing local markets with high-quality 3D printing services. Initially designed to service rapid-prototyping and other niche capabilities, these shops will branch into the consumer marketplace. As retailers begin to “ship the design, not the product,” the local 3D print shop will one day be where you pick up your customized, locally manufactured products, just like you pick up your printed photos from the local Walmart today.
  7. Heated debates on who owns the rights emerge. As manufacturers and designers start to grapple with the prospect of their copyrighted designs being replicated easily on 3D printers, there will be high-profile test cases over the intellectual property of physical object designs. Just like file-sharing sites shook the music industry because they made it easy to copy and share music, the ability to easily copy, share, modify and print 3D objects will ignite a new wave of intellectual property issues.
  8. New products with magical properties will tantalize us. New products – that can only be created on 3D printers – will combine new materials, nano scale and printed electronics to exhibit features that seem magical compared to today’s manufactured products. These printed products will be desirable and have distinct competitive advantage. The secret sauce is that 3D printing can control material as it is printed, right down to the molecules and atoms. As today’s research is perfected into tomorrow’s commercially available printers, expect exciting and desirable new products with amazing capabilities. The question is: What are these products and who will be selling them?
  9. New machines grace the factory floor. Expect to see 3D printing machines appearing in factories. Already some niche components are produced more economically on 3D printers, but this is only on a small scale. Many manufacturers will begin experimenting with 3D printing for applications outside of prototyping. As the capabilities of 3D printers develop and manufacturers gain experience in integrating them into production lines and supply chains, expect hybrid manufacturing processes that incorporate some 3D-printed components. This will be further fueled by consumers desiring products that require 3D printers for their manufacture.
  10. “Look what I made!” Your children will bring home 3D printed projects from school. Digital literacy – including Web and app development, electronics, collaboration and 3D design – will be supported by 3D printers in schools. A number of middle schools and high schools already have 3D printers. As 3D printing costs continue to fall, more schools will sign on. Digital literacy will be about things as well as bits.

If, as President Obama believes, a manufacturing revolution, led by 3D printing, is coming, it behooves business leaders in every field to ask themselves how it could affect their business model and assumptions about the future.


Research Leads to the 3D Printing of Pure Graphene Nanostructures

http://www.33rdsquare.com/2014/12/research-leads-to-3d-printing-of-pure.html

Graphene

Researchers in Korea have successfully 3D printed graphene nano-structures without the use of any other material. With the entire printed structure being composed of graphene, the strength, as well as full conductivity of the material can be taken advantage of.

3d printing graphene

3d printing graphene

https://pharmaceuticalintelligence.files.wordpress.com/2015/09/8d75d-3d2bprinting2bgraphene.jpg

There is no question that graphene, has enormous potential, from solar cell technology, to electronics to medicine.  A key factor in developing practical and commercial applications of the one-atom thick carbon sheets is in aligning the material in the desired form depending on the application.

Now 3D printing of graphene is nearing a feasible stage and companies such as Graphene 3D Lab, are at the forefront of the technology.

However, there is a difference between 3D printing pure graphene, and 3D printing a graphene/thermoplastic composites like Graphene 3D has been doing.

While printing with composite materials, using a typical FDM/FFF or powder based laser sintering process, will keep some of graphene’s superior properties intact, most will be lost. The plastic will eventually break down leaving any prints weak, and not much different from a typical object you’d print with a MakerBot Replicator.

Now, researchers, led by Professor Seung Kwon Seol from Korea Electrotechnology Research Institute (KERI), recentlypublished a paper in Advanced Materials where they describe a new process of directly 3D printing pure graphene.

Their techniques mean that graphene nano-structures can be fabricated without the use of any other material. With the entire printed structure being composed of graphene, the strength, as well as full conductivity of the material can be realized.

“We are convinced that this approach will present a new paradigm for implementing 3D patterns in printed electronics.”

“We developed a nanoscale 3D printing approach that exploits a size-controllable liquid meniscus to fabricate 3D reduced graphene oxide (rGO) nanowires,” Seol told Nanowerk. “Different from typical 3D printing approaches which use filaments or powders as printing materials, our method uses the stretched liquid meniscus of ink. This enables us to realize finer printed structures than a nozzle aperture, resulting in the manufacturing of nanostructures.”
“So far, to the best of our knowledge, nobody has reported 3D printed nanostructures composed entirely of graphene,” says Seol. “Several results reported the 3D printing (millimeter- or centimeter-scale) of graphene or carbon nanotube/plastic composite materials by using a conventional 3D printer. In such composite system, the graphene (or CNT) plays an important role for improving the properties of plastic materials currently used in 3D printers. However, the plastic materials used for producing the composite structures deteriorate the intrinsic properties of graphene (or CNT).”

“We are convinced that this approach will present a new paradigm for implementing 3D patterns in printed electronics,” says Seol.

For their technique, the team grew graphene oxide (GO) wires at room temperature using the meniscus formed at the tip of a micropipette filled with a colloidal dispersion of GO sheets, then reduced it by thermal or chemical treatment (with hydrazine).

The deposition of GO was obtained by pulling the micropipette as the solvent rapidly evaporated, thus enabling the growth of GO wires. The researchers were able to accurately control the radius of the rGO wires by tuning the pulling rate of the pipette; they managed to reach a minimum value of ca. 150 nm.

Using this technique, they were able to produce arrays of different freestanding rGO architectures, grown directly at chosen sites and in different directions: straight wires, bridges, suspended junctions, and woven structures.

Seol points out that this 3D nanoprinting approach can be used for manufacturing 2D patterns and 3D geometry in diverse devices such as printed circuit boards, transistors, light emitting devices, solar cells, sensors and so on.

A lot of work remains to reduce the 3D printable size to below 10 nm and increase the production yield. A short video of Seol’s process is below:

https://youtu.be/cVdFzQu0uMc

Nanoparticle Solar Cells May Drive Down Price of Solar Cells

http://www.33rdsquare.com/2013/09/nanoparticle-solar-cells-may-drive-down.html

University of Alberta researchers have found that abundant materials in the Earth’s crust can be used to make inexpensive and easily manufactured nanoparticle-based solar cells.

The research, which was supported by the Natural Sciences and Engineering Research Council of Canada, is published in the latest issue of ACS Nano.

The discovery, several years in the making, is an important step forward in making solar power more accessible to parts of the world that are off the traditional electricity grid or face high power costs, such as the Canadian North, said researcher Jillian Buriak, a chemistry professor and senior research officer of the National Institute for Nanotechnology based on the U of A campus.

Buriak and her team have designed nanoparticles that absorb light and conduct electricity from two very common elements: phosphorus and zinc. Both materials are more plentiful than scarce materials such as cadmium and are free from manufacturing restrictions imposed on lead-based nanoparticles.

“Half the world already lives off the grid, and with demand for electrical power expected to double by the year 2050, it is important that renewable energy sources like solar power are made more affordable by lowering the costs of manufacturing,” Buriak said.

“My goal is that a store like Ikea could sell rolls of these things with simple instructions and baggies of screws and do-dads and you could install them yourself,” said Buriak
Her team’s research supports a promising approach of making solar cells cheaply using mass manufacturing methods like roll-to-roll printing (as with newspaper presses) or spray-coating (similar to automotive painting). “Nanoparticle-based ‘inks’ could be used to literally paint or print solar cells or precise compositions,” Buriak said.

Buriak collaborated with U of A post-doctoral fellows Erik Luber of the U of A Faculty of Engineering and Hosnay Mobarok of the Faculty of Science to create the nanoparticles. The team was able to develop a synthetic method to make zinc phosphide nanoparticles, and demonstrated that the particles can be dissolved to form an ink and processed to make thin films that are responsive to light.

Buriak and her team are now experimenting with the nanoparticles, spray-coating them onto large solar cells to test their efficiency. The team has applied for a provisional patent and has secured funding to enable the next step to scale up for manufacturing.

Graphene-Based Solar Cells Get Major Boost

http://www.33rdsquare.com/2013/10/graphene-based-solar-cells-get-major.html

graphene on silicon

graphene on silicon

https://pharmaceuticalintelligence.files.wordpress.com/2015/09/25063-grapheneonsilicon.jpg
raphene has extreme conductivity and is completely transparent while being inexpensive and nontoxic. This makes it a perfect candidate material for transparent contact layers for use in solar cells to conduct electricity without reducing the amount of incoming light – at least in theory. Whether or not this holds true in a real world setting is questionable as there is no such thing as “ideal” graphene – a free floating, flat honeycomb structure consisting of a single layer of carbon atoms: interactions with adjacent layers can change graphene’s properties dramatically.

The research recently appeared in the journal Applied Physics Letters.

“We examined how graphene’s conductive properties change if it is incorporated into a stack of layers similar to a silicon based thin film solar cell and were surprised to find that these properties actually change very little,” Marc Gluba explains.

To this end, they grew graphene on a thin copper sheet, next transferred it to a glass substrate, and finally coated it with a thin film of silicon. They examined two different versions that are commonly used in conventional silicon thin-film technologies: onesample contained an amorphous silicon layer, in which the silicon atoms are in a disordered state similar to a hardened molten glass; the other sample contained poly-crystalline silicon to help them observe the effects of a standard crystallization process on graphene‘s properties.
Even though the morphology of the top layer changed completely as a result of being heated to a temperature of several hundred degrees Celcius, the graphene is still detectable. “That’s something we didn’t expect to find, but our results demonstrate that graphene remains graphene even if it is coated with silicon,” says Norbert Nickel.

Their measurements of carrier mobility using the Hall-effect showed that the mobility of charge carriers within the embedded graphene layer is roughly 30 times greater than that of conventional zinc oxide based contact layers.

Says Gluba: “Admittedly, it’s been a real challenge connecting this thin contact layer, which is but one atomic layer thick, to external contacts. We’re still having to work on that.” Adds Nickel: “Our thin film technology colleagues are already pricking up their ears and wanting to incorporate it.” The researchers obtained their measurements on one square centimeter samples, although in practice it is feasible to coat much larger areas than that with graphene.

SOURCE  Helmholtz Zentrum Berlin

Fabricated data bodies: Reflections on 3D printed digital body objects in medical and health domains

Deborah Lupton

Social Theory & Health 13, 99-115 (May 2015) | http://dx.doi.org:/10.1057/sth.2015.3

The advent of 3D printing technologies has generated new ways of representing and conceptualizing health and illness, medical practice and the body. There are many social, cultural and political implications of 3D printing, but a critical sociology of 3D printing is only beginning to emerge. In this article I seek to contribute to this nascent literature by addressing some of the ways in which 3D printing technologies are being used to convert digital data collected on human bodies and fabricate them into tangible forms that can be touched and held. I focus in particular on the use of 3D printing to manufacture non-organic replicas of individuals’ bodies, body parts or bodily functions and activities. The article is also a reflection on a specific set of digital data practices and the meaning of such data to individuals. In analyzing these new forms of human bodies, I draw on sociomaterialist perspectives as well as the recent work of scholars who have sought to theorize selfhood, embodiment, place and space in digital society and the nature of people’s interactions with digital data. I argue that these objects incite intriguing ways of thinking about the ways in digital data on embodiment, health and illnesses are interpreted and used across a range of contexts. The article ends with some speculations about where these technologies may be headed and outlining future research directions.

Osteoconduction and osteoinduction of low-temperature 3D printed bioceramic implants.

Habibovic PGbureck UDoillon CJBassett DCvan Blitterswijk CABarralet JE

Europe Pubmed Central    http://dx.doi.org:/10.1016/j.biomaterials.2007.10.023

Rapid prototyping is a valuable implant production tool that enables the investigation of individual geometric parameters, such as shape, porosity, pore size and permeability, on the biological performance of synthetic bone graft substitutes. In the present study, we have employed low-temperature direct 3D printing to produce brushite and monetite implants with different geometries. Blocks predominantly consisting of brushite with channels either open or closed to the exterior were implanted on the decorticated lumbar transverse processes of goats for 12 weeks. In addition, similar blocks with closed channel geometry, consisting of either brushite or monetite were implanted intramuscularly. The design of the channels allowed investigation of the effect of macropore geometry (open and closed pores) and osteoinduction on bone formation orthotopically. Intramuscular implantation resulted in bone formation within the channels of both monetite and brushite, indicating osteoinductivity of these resorbable materials. Inside the blocks mounted on the transverse processes, initial channel shape did not seem to significantly influence the final amount of formed bone and osteoinduction was suggested to contribute to bone formation.

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Author, reporter, Curator: Tilda Barliya PhD

Dr. Ritu Saxena’s exciting report on the fascinating work of Dr. Apostolia M. Tsimberidou “personalized medicine gearing up to tackle cancer”, inspired me to go back and review this topic and see how nanotechnology can be applied in personalized medicine.

To read the Dr. Saxena’s post, please see https://pharmaceuticalintelligence.com/2013/01/07/personalized-medicine-gearing-up-to-tackle-cancer/

It is based on an interview with Dr. A. M. Tsimberidou based on her paper:

Personalized medicine in a phase I clinical trials program: the MD Anderson Cancer Center initiative.

http://www.ncbi.nlm.nih.gov/pubmed?term=22966018

In March 2011 Nature Reviews issued a special issue features discussions of the advances, challenges and progress in the field of personalized cancer medicine by key opinion leaders who presented at the Worldwide Innovative Networking (WIN) symposium (**).

So what is personalized medicine?

Personalized medicine is a huge movement in the modern medical world. It aims to move away from the traditional practice of prescribing standard doses of standard drugs for a condition to every patient, and shifts the focus onto targeting the precise drug and dose required according to the patient’s physiology.

This is achieved by detecting and tracking molecular biomarkers, which indicate the presence and level of activity of a particular biological system in a patient’s body, whether inherent or foreign.

Another major part of the emerging field of personalized medicine is pharmacogenomics – analyzing the genetic makeup of the patient to determine whether a particular medication will be successful, or if it will have any adverse effects. (1). This is particularly important in cancer treatment, where the chemotherapy drugs used can be very damaging to healthy cells as well as cancerous ones, and the exact genetics of the tumor cells can vary widely between patients, and even between locations in one patient’s body.

Personalized medicine involves:

  • Detection (DNA polymorphism, RNA and protein expression, metabolits, Lipids etc)
  • Diagnosis (imaging)
  • Prognosis and
  • Treatment (targeted-therapy)

Given the size symmetry, nanomaterials offer unprecedented sensitivity, capable of sensing  biological markers and processes at the single-molecule or  single-cell level either in vitro or in vivo.  Techniques are being developed for high-throughput DNA sequencing using nanopores, to obtain genetic information from a patient so that targeted medication can be selected as rapidly as possible.

Cancer, a very complex disease, is propagated by various types of molecular aberrations which drive the development and progression of malignancies. Large-scale screenings of multiple types of molecular aberrations (e.g., mutations, copy number variations, DNA methylations, gene expressions) become increasingly important in the prognosis and study of cancer. Consequently, a computational model integrating multiple types of information is essential for the analysis of the comprehensive data.

One of the greatest promises of near-term nanotechnoloogy is cheaper DNA sequencing to speed the development of personalized medicine. (3)

Nanotechnology and DNA sequencing

Tumors are known to be highly heterogenetic, due to the many acquired aberration in the cancer cells. Therefore,  there are not only genetic differences between different patients, but also genetic differences within the same patient; for example from different locations in the same patient, that can greatly affect the success of a therapy.  Therefore, sensitive and extensive yet inexpensive whole-genome sequencing is of major medical need to enable the application personalized medicine.  A review of the potential of this emerging nanotechnology “Nanopore sensors for nucleic acid analysis ” was published recently in Nature Nanotechnology (4).

The growing need for cheaper and faster genome sequencing has prompted the development of new technologies that surpass conventional Sanger chain-termination methods in terms of speed and cost.  These second- and third-generation sequencing  technologies — inspired by the $1,000 genome challenge proposed by the National Institutes of Health in 2004 (ref. 5) — are expected to revolutionize genomic medicine. Nanopore sensors are one of a number of DNA sequencing technologies that are currently poised to meet this challenge.

Nanopore Sequencing:

Nanopore-based sensing is attractive for DNA sequencing applications because it is a

  • label-free,
  • amplification-free,
  • single-molecule
  • requires low reagent volumes

approach that can be scaled for high-throughput DNA analysis.

This approach can be scaled up for high-throughput DNA analysis, it typically requires low reagent volumes, benefits from
relatively low cost and supports long read lengths, so it could potentially enable de novo sequencing and long-range haplotype mapping. Although, nanopore technology is not conceptually new and raised many skeptical opinions it has made major progress in the past few years and are thus worth sharing.

The principle of nanopore sensing is analogous to that of a Coulter counter. A nanoscale aperture (the nanopore) is formed in an insulating membrane separating two chambers filled with conductive electrolyte. Charged molecules (A,G,C,T) are driven through the pore under an applied electric potential (a process known as electrophoresis), thereby modulating the ionic current through the nanopore. This current reveals useful information about the structure and dynamic motion of the molecule.

Here’s an example for  a nanopore-based sequencing device is a Graphene- chip that is used as trans-electrode membrane (5).

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Electrical measurements on graphene membranes in which a single nanopore has been drilled show that the membrane’s effective insulating thickness is less than one nanometer. This small effective thickness makes graphene an ideal substrate for very high-resolution, high throughput nanopore-based single molecule detectors. The sensitivity of graphene’s in-plane electronic conductivity to its immediate surface environment, as influenced by trans-electrode potential, will offer new insights into atomic surface processes and sensor development opportunities. (4-6).

A nanopore-based diagnostic tool could offer various advantages:

  • it could detect target molecules at very low concentrations from very small sample volumes;
  • it could simultaneously screen panels of biomarkers or genes (which is important in disease diagnosis,
  • monitoring progression and prognosis);
  • it could provide rapid analysis at relatively low cost; and
  • it could eliminate cumbersome amplification and conversion steps such as PCR, bisulphite conversion and Sanger sequencing

Nanopores are likely to have an increasing role in medical diagnostics and DNA sequencing in years to come, but they will face competition from a number of other techniques. These include

  • single-molecule evanescent field detection of sequencing-by-synthesis in arrays of nanochambers (Pacific Biosciences),
  • sequencing by ligation on self-assembled DNA nanoarrays (Complete Genomics), and the
  • detection of H+ ions released during sequencing-by-synthesis on silicon field-effect transistors from multiple polymerase-template reactions (Ion Torrent).

However, the possibility of using nanopore-based sensors to perform long base reads on unlabelled ssDNA molecules in a rapid and costeffective manner could revolutionize genomics and personalized medicine.

Current trends suggest that many challenges in sequencing with biological nanopores

  • the high translocation velocity and the
  • lack of nucleotide specificity

have been resolved. Similarly, given the progress with solid-state nanopores, if the

  • translocation velocity could be reduced to a single nucleotide (which is ~3Å long) per millisecond, and if
  • nucleotides could be identified uniquely with an electronic signature (an area of intense research),

it would be possible to sequence a molecule containing one million bases in less than 20 minutes. Furthermore, if this technology could be scaled to an array of 100,000 individually addressed nanopores operating in parallel, it would be possible to sequence an entire human genome (some three billion base pairs) with 50-fold coverage in less than one hour.

Although, none of the nanopore-solid base sequencing technique have been used as a tool in a clinical trial, one UK-based biotechnology company has its way, nanopore sequencing may soon be available to the public. Earlier this year 2012 Oxford Nanopore Technologies (ONT) announced that it was on the verge of manufacturing a commercial nanopore sensor. [The company said that by year’s end it would release a $900 handheld model, which it claims can sequence a virus genome 48 000 bases long, and a larger, scalable model that could decode a human genome in as little as 15 minutes. In contrast, conventional systems cost upward of $500 000 and take weeks to sequence a human genome (7).]

REFERENCES

** http://www.nature.com/nrclinonc/focus/personalized-medicine/index.html

1. http://www.azonano.com/article.aspx?ArticleID=3078

2. G.E. Marchant. Small is Beautiful: What Can Nanotechnology Do for Personalized Medicine?. Current Pharmacogenomics and Personalized Medicine, 2009, 7, 231-237http://www.benthamscience.com/cppm/Sample/cppm7-4/002AF.pdf

3. http://www.foresight.org/nanodot/?p=4992

4. Venkatesan BM and Bashi R. Nanopore sensors for nucleic acid analysis. Nature Nanotechnology 2011; 18: http://libna.mntl.illinois.edu/pdf/publications/127_venkatesan.pdf

5. Garaj S., Hubbard W., Reina A., King J., Branton D and Golovchenko JA. Graphene as a sub-nanometer trans-electrode membrane. Nature 2010 (9) 467(7312): 190-193. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2956266/

6. Min SK., Kim WY., Cho Y and Kim KS. Fast DNA sequencing with a graphene-based nanochannel device. Nature Nanotechnology 2011; 6: 162-165.  http://biophy.nju.edu.cn/lablog/wp-content/uploads/2011/10/Fast-DNA-sequencing-with-a-graphene-based.pdf

7. http://www.physicstoday.org/resource/1/phtoad/v65/i11/p29_s1?bypassSSO=1

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