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Archive for the ‘Drug Development using MultiOrgan Chip’ Category


3-D Printed Liver

Curator: Larry H. Bernstein, MD, FCAP

 

 

3D-printing a new lifelike liver tissue for drug screening

Could let pharmaceutical companies quickly do pilot studies on new drugs
February 15, 2016    http://www.kurzweilai.net/3d-printing-a-new-lifelike-liver-tissue-for-drug-screening

Images of the 3D-printed parts of the biomimetic liver tissue: liver cells derived from human induced pluripotent stem cells (left), endothelial and mesenchymal supporing cells (center), and the resulting organized combination of multiple cell types (right). (credit: Chen Laboratory, UC San Diego)

 

University of California, San Diego researchers have 3D-printed a tissue that closely mimics the human liver’s sophisticated structure and function. The new model could be used for patient-specific drug screening and disease modeling and could help pharmaceutical companies save time and money when developing new drugs, according to the researchers.

The liver plays a critical role in how the body metabolizes drugs and produces key proteins, so liver models are increasingly being developed in the lab as platforms for drug screening. However, so far, the models lack both the complex micro-architecture and diverse cell makeup of a real liver. For example, the liver receives a dual blood supply with different pressures and chemical constituents.

So the team employed a novel bioprinting technology that can rapidly produce complex 3D microstructures that mimic the sophisticated features found in biological tissues.

The liver tissue was printed in two steps.

  • The team printed a honeycomb pattern of 900-micrometer-sized hexagons, each containing liver cells derived from human induced pluripotent stem cells. An advantage of human induced pluripotent stem cells is that they are patient-specific, which makes them ideal materials for building patient-specific drug screening platforms. And since these cells are derived from a patient’s own skin cells, researchers don’t need to extract any cells from the liver to build liver tissue.
  • Then, endothelial and mesenchymal supporting cells were printed in the spaces between the stem-cell-containing hexagons.

The entire structure — a 3 × 3 millimeter square, 200 micrometers thick — takes just seconds to print. The researchers say this is a vast improvement over other methods to print liver models, which typically take hours. Their printed model was able to maintain essential functions over a longer time period than other liver models. It also expressed a relatively higher level of a key enzyme that’s considered to be involved in metabolizing many of the drugs administered to patients.

“It typically takes about 12 years and $1.8 billion to produce one FDA-approved drug,” said Shaochen Chen, NanoEngineering professor at the UC San Diego Jacobs School of Engineering. “That’s because over 90 percent of drugs don’t pass animal tests or human clinical trials. We’ve made a tool that pharmaceutical companies could use to do pilot studies on their new drugs, and they won’t have to wait until animal or human trials to test a drug’s safety and efficacy on patients. This would let them focus on the most promising drug candidates earlier on in the process.”

The work was published the week of Feb. 8 in the online early edition of Proceedings of the National Academy of Sciences.


Abstract of Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting

The functional maturation and preservation of hepatic cells derived from human induced pluripotent stem cells (hiPSCs) are essential to personalized in vitro drug screening and disease study. Major liver functions are tightly linked to the 3D assembly of hepatocytes, with the supporting cell types from both endodermal and mesodermal origins in a hexagonal lobule unit. Although there are many reports on functional 2D cell differentiation, few studies have demonstrated the in vitro maturation of hiPSC-derived hepatic progenitor cells (hiPSC-HPCs) in a 3D environment that depicts the physiologically relevant cell combination and microarchitecture. The application of rapid, digital 3D bioprinting to tissue engineering has allowed 3D patterning of multiple cell types in a predefined biomimetic manner. Here we present a 3D hydrogel-based triculture model that embeds hiPSC-HPCs with human umbilical vein endothelial cells and adipose-derived stem cells in a microscale hexagonal architecture. In comparison with 2D monolayer culture and a 3D HPC-only model, our 3D triculture model shows both phenotypic and functional enhancements in the hiPSC-HPCs over weeks of in vitro culture. Specifically, we find improved morphological organization, higher liver-specific gene expression levels, increased metabolic product secretion, and enhanced cytochrome P450 induction. The application of bioprinting technology in tissue engineering enables the development of a 3D biomimetic liver model that recapitulates the native liver module architecture and could be used for various applications such as early drug screening and disease modeling.

Fernando

I wonder how equivalent are these hepatic cells derived from human induced pluripotent stem cells (hiPSCs) compared with the real hepatic cell populations.
All cells in our organism share the same DNA info, but every tissue is special for what genes are expressed and also because of the specific localization in our body (which would mean different surrounding environment for each tissue). I am not sure about how much of a step forward this is. Induced hepatic cells are known, but this 3-D print does not have liver shape or the different cell sub-types you would find in the liver.

I agree with your observation that having the same DNA information doesn’t account for variability of cell function within an organ. The regulation of expression is in RNA translation, and that is subject to regulatory factors related to noncoding RNAs and to structural factors in protein folding. The result is that chronic diseases that are affected by the synthetic capabilities of the liver are still problematic – toxicology, diabetes, and the inflammatory response, and amino acid metabolism as well. Nevertheless, this is a very significant step for the testing of pharmaceuticals. When we look at the double circulation of the liver, hypoxia is less of an issue than for heart or skeletal muscle, or mesothelial tissues. I call your attention to the outstanding work by Nathan O. Kaplan on the transhydrogenases, and his stipulation that there are significant differences between organs that are anabolic and those that are catabolic in TPNH/DPNH, that has been ignored for over 40 years. Nothing is quite as simple as we would like.

Fernando commented on 3-D printed liver

3-D printed liver Larry H. Bernstein, MD, FCAP, Curator LPBI 3D-printing a new lifelike liver tissue for drug …

I wonder how equivalent are these hepatic cells derived from human induced pluripotent stem cells (hiPSCs) compared with the real hepatic cell populations.
All cells in our organism share the same DNA info, but every tissue is special for what genes are expressed and also because of the specific localization in our body (which would mean different surrounding environment for each tissue). I am not sure about how much of a step forward this is. Induced hepatic cells are known, but this 3-D print does not have liver shape or the different cell sub-types you would find in the liver.

 

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Human Factor Engineering: New Regulations Impact Drug Delivery, Device Design And Human Interaction

Curator: Stephen J. Williams, Ph.D.

Institute of Medicine report brought medical errors to the forefront of healthcare and the American public (Kohn, Corrigan, & Donaldson, 1999) and  estimated that between

44,000 and 98,000 Americans die each year as a result of medical errors

An obstetric nurse connects a bag of pain medication intended for an epidural catheter to the mother’s intravenous (IV) line, resulting in a fatal cardiac arrest. Newborns in a neonatal intensive care unit are given full-dose heparin instead of low-dose flushes, leading to threedeaths from intracranial bleeding. An elderly man experiences cardiac arrest while hospitalized, but when the code blue team arrives, they are unable to administer a potentially life-saving shock because the defibrillator pads and the defibrillator itself cannot be physically connected.

Human factors engineering is the discipline that attempts to identify and address these issues. It is the discipline that takes into account human strengths and limitations in the design of interactive systems that involve people, tools and technology, and work environments to ensure safety, effectiveness, and ease of use.

 

FDA says drug delivery devices need human factors validation testing

Several drug delivery devices are on a draft list of med tech that will be subject to a final guidance calling for the application of human factors and usability engineering to medical devices. The guidance calls called for validation testing of devices, to be collected through interviews, observation, knowledge testing, and in some cases, usability testing of a device under actual conditions of use. The drug delivery devices on the list include anesthesia machines, autoinjectors, dialysis systems, infusion pumps (including implanted ones), hemodialysis systems, insulin pumps and negative pressure wound therapy devices intended for home use. Studieshave consistently shown that patients struggle to properly use drug delivery devices such as autoinjectors, which are becoming increasingly prevalent due to the rise of self-administered injectable biologics. The trend toward home healthcare is another driver of usability issues on the patient side, while professionals sometimes struggle with unclear interfaces or instructions for use.

 

Humanfactors engineering, also called ergonomics, or human engineering, science dealing with the application of information on physical and psychological characteristics to the design of devices and systems for human use. ( for more detail see source@ Britannica.com)

The term human-factors engineering is used to designate equally a body of knowledge, a process, and a profession. As a body of knowledge, human-factors engineering is a collection of data and principles about human characteristics, capabilities, and limitations in relation to machines, jobs, and environments. As a process, it refers to the design of machines, machine systems, work methods, and environments to take into account the safety, comfort, and productiveness of human users and operators. As a profession, human-factors engineering includes a range of scientists and engineers from several disciplines that are concerned with individuals and small groups at work.

The terms human-factors engineering and human engineering are used interchangeably on the North American continent. In Europe, Japan, and most of the rest of the world the prevalent term is ergonomics, a word made up of the Greek words, ergon, meaning “work,” and nomos, meaning “law.” Despite minor differences in emphasis, the terms human-factors engineering and ergonomics may be considered synonymous. Human factors and human engineering were used in the 1920s and ’30s to refer to problems of human relations in industry, an older connotation that has gradually dropped out of use. Some small specialized groups prefer such labels as bioastronautics, biodynamics, bioengineering, and manned-systems technology; these represent special emphases whose differences are much smaller than the similarities in their aims and goals.

The data and principles of human-factors engineering are concerned with human performance, behaviour, and training in man-machine systems; the design and development of man-machine systems; and systems-related biological or medical research. Because of its broad scope, human-factors engineering draws upon parts of such social or physiological sciences as anatomy, anthropometry, applied physiology, environmental medicine, psychology, sociology, and toxicology, as well as parts of engineering, industrial design, and operations research.

source@ Britannica.com

The human-factors approach to design

Two general premises characterize the approach of the human-factors engineer in practical design work. The first is that the engineer must solve the problems of integrating humans into machine systems by rigorous scientific methods and not rely on logic, intuition, or common sense. In the past the typical engineer tended either to ignore the complex and unpredictable nature of human behaviour or to deal with it summarily with educated guesses. Human-factors engineers have tried to show that with appropriate techniques it is possible to identify man-machine mismatches and that it is usually possible to find workable solutions to these mismatches through the use of methods developed in the behavioral sciences.

The second important premise of the human-factors approach is that, typically, design decisions cannot be made without a great deal of trial and error. There are only a few thousand human-factors engineers out of the thousands of thousands of engineers in the world who are designing novel machines, machine systems, and environments much faster than behavioral scientists can accumulate data on how humans will respond to them. More problems, therefore, are created than there are ready answers for them, and the human-factors specialist is almost invariably forced to resort to trying things out with various degrees of rigour to find solutions. Thus, while human-factors engineering aims at substituting scientific method for guesswork, its specific techniques are usually empirical rather than theoretical.

HFgeneralpic

 

 

 

 

 

 

 

 

 

 

 

The Man-Machine Model: Human-factors engineers regard humans as an element in systems

The simple man-machine model provides a convenient way for organizing some of the major concerns of human engineering: the selection and design of machine displays and controls; the layout and design of workplaces; design for maintainability; and the work environment.

Components of the Man-Machine Model

  1. human operator first has to sense what is referred to as a machine display, a signal that tells him something about the condition or the functioning of the machine
  2. Having sensed the display, the operator interprets it, perhaps performs some computation, and reaches a decision. In so doing, the worker may use a number of human abilities, Psychologists commonly refer to these activities as higher mental functions; human-factors engineers generally refer to them as information processing.
  3. Having reached a decision, the human operator normally takes some action. This action is usually exercised on some kind of a control—a pushbutton, lever, crank, pedal, switch, or handle.
  4. action upon one or more of these controls exerts an influence on the machine and on its output, which in turn changes the display, so that the cycle is continuously repeated

 

Driving an automobile is a familiar example of a simple man-machine system. In driving, the operator receives inputs from outside the vehicle (sounds and visual cues from traffic, obstructions, and signals) and from displays inside the vehicle (such as the speedometer, fuel indicator, and temperature gauge). The driver continually evaluates this information, decides on courses of action, and translates those decisions into actions upon the vehicle’s controls—principally the accelerator, steering wheel, and brake. Finally, the driver is influenced by such environmental factors as noise, fumes, and temperature.

 

hfactorconsideroutcomes

How BD Uses Human Factors to Design Drug-Delivery Systems

Posted in Design Services by Jamie Hartford on August 30, 2013

 Human factors testing has been vital to the success of the company’s BD Physioject Disposable Autoinjector.

Improving the administration and compliance of drug delivery is a common lifecycle strategy employed to enhance short- and long-term product adoption in the biotechnology and pharmaceutical industries. With increased competition in the industry and heightened regulatory requirements for end-user safety, significant advances in product improvements have been achieved in the injectable market, for both healthcare professionals and patients. Injection devices that facilitate preparation, ease administration, and ensure safety are increasingly prevalent in the marketplace.

Traditionally, human factors engineering addresses individualized aspects of development for each self-injection device, including the following:

  • Task analysis and design.
  • Device evaluation and usability.
  • Patient acceptance, compliance, and concurrence.
  • Anticipated training and education requirements.
  • System resilience and failure.

To achieve this, human factors scientists and engineers study the disease, patient, and desired outcome across multiple domains, including cognitive and organizational psychology, industrial and systems engineering, human performance, and economic theory—including formative usability testing that starts with the exploratory stage of the device and continues through all stages of conceptual design. Validation testing performed with real users is conducted as the final stage of the process.

To design the BD Physioject Disposable Autoinjector System , BD conducted multiple human factors studies and clinical studies to assess all aspects of performance safety, efficiency, patient acceptance, and ease of use, including pain perception compared with prefilled syringes.5 The studies provided essential insights regarding the overall user-product interface and highlighted that patients had a strong and positive response to both the product design and the user experience.

As a result of human factors testing, the BD Physioject Disposable Autoinjector System provides multiple features designed to aide in patient safety and ease of use, allowing the patient to control the start of the injection once the autoinjector is placed on the skin and the cap is removed. Specific design features included in the BD Physioject Disposable Autoinjector System include the following:

  • Ergonomic design that is easy to handle and use, especially in patients with limited dexterity.
  • A 360° view of the drug and injection process, allowing the patient to confirm full dose delivery.
  • A simple, one-touch injection button for activation.
  • A hidden needle before and during injection to reduce needle-stick anxiety.
  • A protected needle before and after injection to reduce the risk of needle stick injury.

 

YouTube VIDEO: Integrating Human Factors Engineering (HFE) into Drug Delivery

 

Notes:

 

 

The following is a slideshare presentation on Parental Drug Delivery Issues in the Future

 The Dangers of Medical Devices

The FDA receives on average 100,000 medical device incident reports per year, and more than a third involve user error.

In an FDA recall study, 44% of medical device recalls are due to design problems, and user error is often linked to the poor design of a product.

Drug developers need to take safe drug dosage into consideration, and this consideration requires the application of thorough processes for Risk Management and Human Factors Engineering (HFE).

Although unintended, medical devices can sometimes harm patients or the people administering the healthcare. The potential harm arises from two main sources:

  1. failure of the device and
  2. actions of the user or user-related errors. A number of factors can lead to these user-induced errors, including medical devices are often used under stressful conditions and users may think differently than the device designer.

Human Factors: Identifying the Root Causes of Use Errors

Instead of blaming test participants for use errors, look more carefully at your device’s design.

Great posting on reasons typical design flaws creep up in medical devices and where a company should integrate fixes in product design.
Posted in Design Services by Jamie Hartford on July 8, 2013

 

 

YouTube VIDEO: Integrating Human Factors Engineering into Medical Devices

 

 

Notes:

 

 Regulatory Considerations

  • Unlike other medication dosage forms, combination products require user interaction
  •  Combination products are unique in that their safety profile and product efficacy depends on user interaction
Human Factors Review: FDA Outlines Highest Priority Devices

Posted 02 February 2016By Zachary Brennan on http://www.raps.org/Regulatory-Focus/News/2016/02/02/24233/Human-Factors-Review-FDA-Outlines-Highest-Priority-Devices/ 

The US Food and Drug Administration (FDA) on Tuesday released new draft guidance to inform medical device manufacturers which device types should have human factors data included in premarket submissions, as well final guidance from 2011 on applying human factors and usability engineering to medical devices.

FDA said it believes these device types have “clear potential for serious harm resulting from use error and that review of human factors data in premarket submissions will help FDA evaluate the safety and effectiveness and substantial equivalence of these devices.”

Manufacturers should provide FDA with a report that summarizes the human factors or usability engineering processes they have followed, including any preliminary analyses and evaluations and human factors validation testing, results and conclusions, FDA says.

The list was based on knowledge obtained through Medical Device Reporting (MDRs) and recall data, and includes:

  • Ablation generators (associated with ablation systems, e.g., LPB, OAD, OAE, OCM, OCL)
  • Anesthesia machines (e.g., BSZ)
  • Artificial pancreas systems (e.g., OZO, OZP, OZQ)
  • Auto injectors (when CDRH is lead Center; e.g., KZE, KZH, NSC )
  • Automated external defibrillators
  • Duodenoscopes (on the reprocessing; e.g., FDT) with elevator channels
  • Gastroenterology-urology endoscopic ultrasound systems (on the reprocessing; e.g., ODG) with elevator channels
  • Hemodialysis and peritoneal dialysis systems (e.g., FKP, FKT, FKX, KDI, KPF ODX, ONW)
  • Implanted infusion pumps (e.g., LKK, MDY)
  • Infusion pumps (e.g., FRN, LZH, MEA, MRZ )
  • Insulin delivery systems (e.g., LZG, OPP)
  • Negative-pressure wound therapy (e.g., OKO, OMP) intended for home use
  • Robotic catheter manipulation systems (e.g., DXX)
  • Robotic surgery devices (e.g., NAY)
  • Ventilators (e.g., CBK, NOU, ONZ)
  • Ventricular assist devices (e.g., DSQ, PCK)

Final Guidance

In addition to the draft list, FDA finalized guidance from 2011 on applying human factors and usability engineering to medical devices.

The agency said it received over 600 comments on the draft guidance, which deals mostly with design and user interface, “which were generally supportive of the draft guidance document, but requested clarification in a number of areas. The most frequent types of comments requested revisions to the language or structure of the document, or clarification on risk mitigation and human factors testing methods, user populations for testing, training of test participants, determining the appropriate sample size in human factors testing, reporting of testing results in premarket submissions, and collecting human factors data as part of a clinical study.”

In response to these comments, FDA said it revised the guidance, which supersedes guidance from 2000 entitled “Medical Device Use-Safety: Incorporating Human Factors Engineering into Risk Management,” to clarify “the points identified and restructured the information for better readability and comprehension.”

Details

The goal of the guidance, according to FDA, is to ensure that the device user interface has been designed such that use errors that occur during use of the device that could cause harm or degrade medical treatment are either eliminated or reduced to the extent possible.

FDA said the most effective strategies to employ during device design to reduce or eliminate use-related hazards involve modifications to the device user interface, which should be logical and intuitive.

In its conclusion, FDA also outlined the ways that device manufacturers were able to save money through the use of human factors engineering (HFE) and usability engineering (UE).

– See more at: http://www.raps.org/Regulatory-Focus/News/2016/02/02/24233/Human-Factors-Review-FDA-Outlines-Highest-Priority-Devices/#sthash.cDTr9INl.dpuf

 

Please see an FDA PowerPoint on Human Factors Regulatory Issues for Combination Drug/Device Products here: MFStory_RAPS 2011 – HF of ComboProds_v4

 

 

 

 

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Current Advances in Medical Technology

Larry H. Bernstein, MD, FCAP, Curator

LPBI

Pumpkin-Shaped Molecule Enables 100-Fold Improved MRI Contrast

Tue, 10/13/2015 – 9:16amby Forschungsverbund Berlin e.V. (FVB)

http://www.mdtmag.com/news/2015/10/pumpkin-shaped-molecule-enables-100-fold-improved-mri-contrast

Assuming that we could visualize pathological processes such as cancer at a very early stage and additionally distinguish the various different cell types, this would represent a giant step for personalized medicine. Xenon magnetic resonance imaging has the potential to fulfil this promise – if suitable contrast media are found that react sensitively enough to the “exposure”. Researchers at the Leibniz-Institut für Molekulare Pharmakologie in Berlin have now found that a class of pumpkin-shaped molecules called cucurbiturils together with the inert gas xenon, enables particularly good image contrast – namely around 100 times better than has been possible up to now. This finding published in the November issue cover article of Chemical Science by the Royal Society of Chemistry points the way to the tailoring of new contrast agents to different cell types and has the potential to enable molecular diagnostics even without tissue samples in the future.

Personalized medicine instead of one treatment for all – especially in cancer medicine, this approach has led to a paradigm shift. Molecular diagnostics is the key that will give patients access to tailor-made therapy. However, if tumors are located in poorly accessible areas of the body or several tumor foci are already present, this often fails due to a lack of sufficient sensitivity of the diagnostic imaging. But such sensitivity is needed to determine the different cell types, which differ considerably even within a tumor. Although even the smallest of tumor foci and other pathological changes can be detected using the PET-CT, a differentiation according to cell type is usually not possible.

Scientists from the FMP are therefore focusing on xenon magnetic resonance imaging: The further development of standard magnetic resonance imaging makes use of the “illuminating power” of the inert gas xenon, which can provide a 10,000-fold enhanced signal in the MRI. To do this, it must be temporarily captured by so-called “cage molecules” in the diseased tissue. This has been more or less successful with the molecules used to date, but the experimental approach is still far from a medical application.

Cucurbituril Provides Stunning Image Contrasts
The research group led by Dr. Leif Schröder at the Leibniz-Institut für Molekulare Pharmakologie (FMP) has now discovered a molecule class for this purpose that eclipses all of the molecules used to date. Cucurbituril exchanges around 100 times more xenon per unit of time than its fellow molecules, which leads to a much better image contrast. “It very quickly became clear that cucurbituril might be suitable as a contrast medium,” reports Leif Schröder. “However, it was surprising that areas marked with it were imaged with a much better contrast than previously.” The explanation is to be found in the speed. Upon exposure, so to speak, cucurbituril generates contrast more rapidly than all molecules used to date, as it only binds the xenon very briefly and thus transmits the radio waves to detect the inert gas to very many xenon atoms within a fraction of a second. In this way, the inert gas is passed through the molecule much more efficiently.

In the study, which appeared in the specialist journal “Chemical Science”, the world’s first MRI images with cucurbituril have been achieved. With the aid of a powerful laser and a vaporized alkali metal, the researchers initially greatly strengthened the magnetic properties of normal xenon. The hyperpolarized gas was then introduced into a test solution with the cage molecules. A subsequent MRI image showed the distribution of the xenon in the object. In a second image, the curcurbituril together with radio waves destroyed the magnetization of the xenon, leading to dark spots on the images.

“Comparison of the two images demonstrates that only the xenon in the cages has the right resonance frequency to produce a dark area,” explains Schröder. “This blackening is possible to a much better degree with cucurbituril than with previous cage molecules, for it works like a very light-sensitive photographic paper. The contrast is around 100 times stronger.”

Time-of-Flight IC Revolutionizes Object Detection and Distance Measurement

Tue, 10/13/2015 – 9:07amby Intersil

New ISL29501 signal processing IC detects objects up to two meters

http://www.mdtmag.com/product-release/2015/10/time-flight-ic-revolutionizes-object-detection-and-distance-measurement
Intersil Corporation has introduced an innovative time-of-flight (ToF) signal processing IC that provides a complete object detection and distance measurement solution when combined with an external emitter (LED or laser) and photodiode. The ISL29501 ToF device offers one-of-a-kind functionality, including ultra-small size, low-power consumption and superior performance ideal for connected devices that make up the Internet of Things (IoT), as well as consumer mobile devices and the emerging commercial drone market.

The ISL29501 overcomes the shortcomings of traditional amplitude-based proximity sensors and other ToF solutions that perform poorly in lighting conditions above 2,000 lux, or cannot provide distance information unless the object is perpendicular to the sensor.

The ISL29501 applies Intersil’s power management expertise to save power and extend battery life through several innovations.

“Prior to Intersil’s time-of-flight technology breakthrough, there was no practical way to measure distance up to two meters in a small form factor,” said Andrew Cowell, senior vice president of Mobile Power Products at Intersil. “The innovative ISL29501 provides customers a cost-effective, small footprint solution that also gives them the flexibility to use multiple devices to increase the field of view to a full 360 degrees for enhanced object detection capabilities.”

Key Features and Specifications

  • On-chip DSP calculates ToF for accurate proximity detection and distance measurement up to two meters
  • Modulation frequency of 4.5MHz prevents interference with other consumer products such as IR TV remote controls that operate at 40kHzOn-chip emitter DAC with programmable current up to 255mA
  • Allows designers to choose the desired current level to optimize distance measurement and power budget
  • Operates in single shot mode for initial object detection and approximate distance measurement, while continuous mode improve distance accuracy
  • On-chip active ambient light rejection minimizes or eliminates the influence of ambient light during distance measurement
  • Programmable distance zones: allows the user to define three ToF distance zones for determining interrupt alerts
  • Interrupt controller generates interrupt alerts using distance measurements and user defined thresholds
  • Automatic gain control sets optimum analog signal levels to achieve best SNR response
  • Supply voltage range of 2.7V to 3.3V
  • I2C interface supports 1.8V and 3.3V bus

The ISL29501 can be combined with the ISL9120 buck-boost regulator to further reduce power consumption and extend battery life in consumer and home automation applications.

Optoelectronic Implantable Could Enable Two-Way Communication with Brain

Mon, 10/12/2015 – 4:04pmby Brown University

http://www.mdtmag.com/news/2015/10/optoelectronic-implantable-could-enable-two-way-communication-brain

Brown University researchers have created a new type of optoelectronic implantable device to access brain microcircuits, synergizing a technique that enables scientists to control the activity of brains cells using pulses of light. The invention, described in the journal Nature Methods, is a cortical microprobe that can stimulate multiple neuronal targets optically by specific patterns on micrometer scale while simultaneously recording the effects of that stimulation in the underlying neural microcircuits of interest with millisecond precision.

“We think this is a window-opener,” said Joonhee Lee, a senior research associate in Professor Arto Nurmikko’s lab in the School of Engineering at Brown and one of the lead authors of the new paper. “The ability to rapidly perturb neural circuits according specific spatial patterns and at the same time reconstruct how the circuits involved are perturbed, is in our view a substantial advance.”

First introduced around 2005, optogenetics has enriched ability of scientists seeking to understand brain function at the neuronal level. The technique involves genetically engineering neurons to express light-sensitive proteins on their membranes. With those proteins expressed, pulses of light can be used to either promote or suppress activity in those particular cells. The method gives researchers in principle unprecedented ability to control specific brain cells at specific times.

But until now, simultaneous optogenetic stimulation and recording of brain activity rapidly across multiple points within a brain microcircuit of interest has proven difficult. Doing it requires a device that can both generate a spatial pattern of light pulses and detect the dynamical patterns of electrical reverberations generated by excited cellular activity. Previous attempts to do this involved devices that cobbled together separate components for light emission and electrical sensing. Such probes were physically bulky, not ideal for insertion into a brain. And because the emitters and the sensors were necessarily a hundreds of micrometers apart, a sizable distance, the link between stimulation and recorded signal was ambiguous.

The new compact, integrated device developed by Nurmikko’s lab begins with the unique advantages endowed by a so-called wide bandgap semiconductor called zinc oxide. It is optically transparent yet able readily to conduct an electrical current.

“Very few materials have that pair of physical properties,” Lee said. “The combination makes it possible to both stimulate and detect with the same material.”

Joonhee Lee, with Assistant Research Professor Ilker Ozden and Professor Yoon-Kyu Song at Seoul National University in Korea, co-developed a novel microfabrication method with Nurmikko to shape the material into a monolithic chip just a few millimeters square with sixteen micrometer sized pin-like “optoelectrodes,” each capable of both delivering light pulses and sensing electrical current. The array of optoelectrodes enables the device to couple to neural microcircuits composed of many neurons rather than single neurons.

Such ability to stimulate and record at the network level on spatial and time scales at which they operate is key, Nurmikko says. Brain functions are driven by neural circuits rather than single neurons.

“For example, when I move my hand, that’s an example of action driven by specific network-level activity in the brain,” he said. “Our new device approach gives scientists and engineers a tool in applying the full power of optogenetics as a means of neural stimulation, while providing the means to read activity of perturbed networks at multiple points at high spatial precision and time resolution.”

Ozden led the initial testing of the device in rodent models. The researchers looked at the extent to which different light intensities could stimulate network activity. The tests showed that increasing optical power led to distinct recruitment of neuronal circuits revealing functional connectivity in the targeted network.

“We went over a range of optical power that was large–over three orders of magnitude–and in so doing we got a range of network-related responses, in particular we could replicate an activity pattern naturally occurring in the brain.” Ozden said. “It gave us a new insight into how optogenetics operates on the network level. This gives us encouragement to go ahead and extend the repertoire and application of the device technology.”

Nurmikko’s group together with the Song lab in Seoul plan to continue further development of the device, ultimately include an access via wireless means. Their next steps anticipate the use of the new device technology as chronic implant in non-human primates at potentially hundreds of points and, depending on progress in worldwide research on optogenetics ahead, perhaps even one day in humans.

“At least, the initial building blocks are here,” Nurmikko said, who conceived the idea with his Korean colleague Song.

Study Advances Possibility of Mind-Controlled Devices

Mon, 10/12/2015 – 10:50amby Ryan Bushey, Associate Editor, R&D

A study published in the journal Nature Medicine has shown a possible path to creating effective neural prosthetics.

http://www.mdtmag.com/blog/2015/10/study-advances-possibility-mind-controlled-devices

The study’s subjects, only listed as T6 and T7, have Amyotropic Lateral Sclerosis (ALS). The scientists performed surgery on them one year ago to place a “neural recording device” in the part of the brain in charge of controlling hand function, notes Bloomberg.

The test documented in the study required T6 and T7 to perform a variety of tasks, such as moving a cursor to hit different targets on a computer screen. The device receives electrical impulses from the brain and morphs them into a computer signal to operate the cursor.

Both test subjects had the highest published performance so far, and even doubled the results of the previous clinical trial participant, according to the study.

The hope is that these devices can improve quality of life for people suffering from paralysis.

You can watch how T6 performed in her test below.

https://youtu.be/9P-qsiIORVU

Removing 62 Barriers to Pig–to–Human Organ Transplant in One Fell Swoop

Mon, 10/12/2015 – 9:09amby Wyss Institute for Biologically Inspired Engineering

The largest number of simultaneous gene edits ever accomplished in the genome could help bridge the gap between organ transplant scarcity and the countless patients who need them

http://www.mdtmag.com/news/2015/10/removing-62-barriers-pig%E2%80%93%E2%80%93human-organ-transplant-one-fell-swoop

Never before have scientists been able to make scores of simultaneous genetic edits to an organism’s genome. But now in a landmark study by George Church, Ph.D., and his team at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard Medical School, the gene editing system known as “CRISPR–Cas9” has been used to genetically engineer pig DNA in 62 locations – an explosive leap forward in CRISPR’s capability when compared to its previous record maximum of just six simultaneous edits. The 62 edits were executed by the team to inactivate retroviruses found natively in the pig genome that have so far inhibited pig organs from being suitable for transplant in human patients. With the retroviruses safely removed via genetic engineering, however, the road is now open toward the possibility that humans could one day receive life–saving organ transplants from pigs.

Church is a Wyss Core Faculty member, the Robert Winthrop Professor of Genetics at Harvard Medical School (HMS) and Professor of Health Sciences and Technology at Harvard and MIT. The advance, reported by Church and his team including the study’s lead author Luhan Yang, Ph.D., a Postdoctoral Fellow at HMS and the Wyss Institute, was published in the October 11 issue of Science.

The concept of xenotransplantation, which is the transplant of an organ from one species to another, is nothing new. Researchers and clinicians have long hoped that one of the major challenges facing patients suffering from organ failure – which is the lack of available organs in the United States and worldwide – could be alleviated through the availability of suitable animal organs for transplant. Pigs in particular have been especially promising candidates due to their similar size and physiology to humans. In fact, pig heart valves are already commonly sterilized and de–cellularized for use repairing or replacing human heart valves.

This artistic rendering shows pig chromosomes (background) which reside in the nucleus of pig cells and contain a single strand of RNA, and the Cas9 protein targeting DNA (foreground). The CRISPR–Cas9 gene editing system works like molecular scissors to precisely edit genes of interest. A new advance reported in Science by Wyss Core Faculty member George Church and his team used Cas9 to make 62 edits to the pig genome to remove latent retroviruses, presenting a solution to one of the largest safety concerns that has so far blocked progress in making pig organs compatible for xenotransplant in humans. (Credit: Wyss Institute at Harvard University)

But the transplant of whole, functional organs comprised of living cells and tissue constructs has presented a unique set of challenges for scientists. One of the primary problems has been the fact that most mammals including pigs contain repetitive, latent retrovirus fragments in their genomes – present in all their living cells – that are harmless to their native hosts but can cause disease in other species.

“The presence of this type of virus found in pigs – known as porcine endogenous retroviruses or PERVs – brought over a billion of dollars of pharmaceutical industry investments into developing xenotransplant methods to a standstill by the early 2000s,” said Church. “PERVs and the lack of ability to remove them from pig DNA was a real showstopper on what had been a promising stage set for xenotransplantation.”

Now – using CRISPR–Cas9 like a pair of molecular scissors – Church and his team have inactivated all 62 repetitive genes containing a PERV in pig DNA, surpassing a significant obstacle on the path to bringing xenotransplantation to clinical reality. With more than 120,000 patients currently in the United States awaiting transplant and less than 30,000 transplants on average occurring annually, xenotransplantation could give patients and clinicians an alternative in the future.

“Pig kidneys can already function experimentally for months in baboons, but concern about the potential risks of PERVs has posed a problem for the field of xenotransplantation for many years,” said David H. Sachs, M.D., Director of the TBRC Laboratories at Massachusetts General Hospital, Paul S. Russell Professor of Surgery Emeritus at Harvard Medical School, and Professor of Surgical Sciences at Columbia University’s Center for Translational Immunology. Sachs has been developing special pigs for xenotransplantation for more than 30 years and is currently collaborating with Church on further genetic modifications of his pigs. “If Church and his team are able to produce pigs from genetically engineered embryos lacking PERVs by the use of CRISPR-Cas9, they would eliminate an important potential safety concern facing this field.”

Yang says the team hopes eventually they can completely eliminate the risk that PERVs could cause disease in clinical xenotransplantation by using modified pig cells to clone a line of pigs that would have their PERV genes inactivated.

“This advance overcomes a major hurdle that has until now halted the progress of xenotransplantation research and development,” said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences. “The real value and potential impact is in the number of lives that could be saved if we can one day use xenotransplants to close the huge gap between the number of available functional organs and the number of people who desperately need them.”

The remarkable and newly demonstrated capability for CRISPR to edit tens of repetitive genes such as PERVs will also unlock new ways for scientists to study and understand repetitive regions in the genome, which has been estimated to comprise more than two–thirds of our own human genome.

Contributors to the work also included: co–lead authors Marc Güell of the Wyss Institute and Harvard Medical School Department of Genetics, Dong Niu of HMS Dept. of Genetics and Zhejiang University’s College of Animal Sciences, and Haydy George of HMS Dept. of Genetics; and co–authors Emal Lesha, Dennis Grishin, Jürgen Poci, Ellen Shrock, and Rebeca Cortazio of HMS Dept. of Genetics, Weihong Xu of Massachusetts General Hospital Department of Surgery, and Robert Wilkinson and Jay Fishman of MGH’s Transplant Infection Disease & Compromised Host Program.

Novel Gut-on-a-Chip Nearly Indistinguishable from Human GI Tract

Fri, 10/09/2015 – 1:17pmby University of North Carolina Healthcare

http://www.mdtmag.com/news/2015/10/novel-gut-chip-nearly-indistinguishable-human-gi-tract?et_cid=4876632&et_rid=535648082

A team of researchers from the University of North Carolina at Chapel Hill and NC State University has received a $5.3 million, five-year Transformative Research (R01) Award from the National Institutes of Health (NIH) to create fully functioning versions of the human gut that fit on a chip the size of a dime.

Such “organs-on-a-chip” have become vital for biomedical research, as researchers seek alternatives to animal models for drug discovery and testing. The new grant will fund a technology that represents a major step forward for the field, overcoming limitations that have mired other efforts.

The technology will use primary cells derived directly from human biopsies, which are known to provide more relevant results than the immortalized cell lines used in current approaches. In addition, the device will sculpt these cells into the sophisticated architecture of the gut, rather than the disorganized ball of cells that are created in other miniature organ systems.

This is a picture of a schematic of colonic epithelial tissue. Crypt units are pointed down, flat surface faces center of the gut tube. Stem cells are red, progenitor cells are pink, differentiated cells are grey, blue and green. Yellow cells are stem cell niche cells. Lumenal surface is above crypts. (Credit: Scott Magness, PhD, UNC School of Medicine)

“We are building a device that goes far beyond the organ-on-a-chip,” said Nancy L. Allbritton, MD, PhD, professor and chair of the UNC-NC State joint department of biomedical engineering and one of four principle investigators on the NIH grant. “We call it a ‘simulacrum,’ a term used in science fiction to describe a duplicate. The idea is to create something that is indistinguishable from your own gut.”

Allbritton is an expert at microfabrication and microengineering. Also on the team are intestinal stem cell expert Scott T. Magness, PhD, associate professor of medicine, biomedical engineering, and cell and molecular physiology in the UNC School of Medicine; microbiome expert Scott Bultman, PhD, associate professor of genetics in the UNC School of Medicine; and bioinformatics expert Shawn Gomez, associate professor of biomedical engineering at UNC-Chapel Hill and NC State.

The impetus for the “organ-on-chip” movement comes largely from the failings of the pharmaceutical industry. For just a single drug to go through the discovery, testing, and approval process can take as many as 15 years and as much as $5 billion dollars. Animal models are expensive to work with and often don’t respond to drugs and diseases the same way humans do. Human cells grown in flat sheets on Petri dishes are also a poor proxy. Three-dimensional “organoids” are an improvement, but these hollow balls are made of a mishmash of cells that doesn’t accurately mimic the structure and function of the real organ.

Basically, the human gut is a 30-foot long hollow tube made up of a continuous single-layer of specialized cells. Regenerative stem cells reside deep inside millions of small pits or “crypts” along the tube, and mature differentiated cells are linked to the pits and live further out toward the surface. The gut also contains trillions of microbes, which are estimated to outnumber human cells by ten to one. These diverse microbial communities — collectively known as the microbiota — process toxins and pharmaceuticals, stimulate immunity, and even release hormones to impact behavior.

These are fluorescent images of the side view of two synthetic crypts. Blue: nuclei of the cells. Red: proliferating stem cells in similar location to those in the human colon. (Credit: Scott Magness, PhD, UNC School of Medicine)

To create a dime-sized version of this complex microenvironment, the UNC-NC State team borrowed fabrication technologies from the electronics and microfluidics world. The device is composed of a polymer base containing an array of imprinted or shaped “hydrogels,” a mesh of molecules that can absorb water like a sponge. These hydrogels are specifically engineered to provide the structural support and biochemical cues for growing cells from the gut. Plugged into the device will be various kinds of plumbing that bring in chemicals, fluids, and gases to provide cues that tell the cells how and where to differentiate and grow. For example, the researchers will engineer a steep oxygen gradient into the device that will enable oxygen-loving human cells and anaerobic microbes to coexist in close proximity.

“The underlying concept — to simply grow a piece of human tissue in a dish — doesn’t seem that groundbreaking,” said Magness. “We have been doing that for a long time with cancer cells, but those efforts do not replicate human physiology. Using native stem cells from the small intestine or colon, we can now develop gut tissue layers in a dish that contains stem cells and all the differentiated cells of the gut. That is the thing stem cell biologists and engineers have been shooting for, to make real tissue behave properly in a dish to create better models for drug screening and cell-based therapies. With this work, we made a big leap toward that goal.”

Right now, the team has a working prototype that can physically and chemically guide mouse intestinal stem cells into the appropriate structure and function of the gut. For several years, Magness has been isolating and banking human stem cells from samples from patients undergoing routine colonoscopies at UNC Hospitals. As part of the grant, he will work with the rest of the team to apply these stem cells to the new device and create “simulacra” that are representative of each patient’s individual gut. The approach will enable researchers to explore in a personalized way how both the human and microbial cells of the gut behave during healthy and diseased states.

“Having a system like this will advance microbiota research tremendously,” said Bultman. “Right now microbiota studies involve taking samples, doing sequencing, and then compiling an inventory of all the microbes in the disease cases and healthy controls. These studies just draw associations, so it is difficult to glean cause and effect. This device will enable us to probe the microbiota, and gain a better understanding of whether changes in these microbial communities are the cause or the consequence of disease.”

On-Chip Optical Sensing Technique Detects Multiple Flu Strains

Tue, 10/06/2015 – 10:11amby University of California – Santa Cruz

http://www.mdtmag.com/news/2015/10/chip-optical-sensing-technique-detects-multiple-flu-strains?et_cid=4876632&et_rid=535648082

A schematic view shows the optical waveguide intersecting a fluidic microchannel containing target particles. Targets are optically excited as they flow past well-defined excitation spots created by multi-mode interference; fluorescence is collected by the liquid-core waveguide channel and routed into solid-core waveguides (red). (Credit: Ozcelik et al., PNAS 2015)

New chip-based optical sensing technologies developed by researchers at UC Santa Cruz and Brigham Young University enable the rapid detection and identification of multiple biomarkers. In a paper published October 5 in Proceedings of the National Academy of Sciences, researchers describe a novel method to perform diagnostic assays for multiple strains of flu virus on a small, dedicated chip.

“A standard flu test checks for about ten different flu strains, so it’s important to have an assay that can look at ten to 15 things at once. We showed a completely new way to do that on an optofluidic chip,” said senior author Holger Schmidt, the Kapany Professor of Optoelectronics in the Baskin School of Engineering at UC Santa Cruz.

Over the past decade, Schmidt and his collaborators at BYU have developed chip-based technology to optically detect single molecules without the need for high-end laboratory equipment. Diagnostic instruments based on their optofluidic chips could provide a rapid, low-cost, and portable option for identifying specific disease-related molecules or virus particles.

In the new study, Schmidt demonstrated a novel application of a principle called wavelength division multiplexing, which is widely used in fiber-optic communications. By superimposing multiple wavelengths of light in an optical waveguide on a chip, he was able to create wavelength-dependent spot patterns in an intersecting fluidic channel. Virus particles labeled with fluorescent markers give distinctive signals as they pass through the fluidic channel depending on which wavelength of light the markers absorb.

“Each color of light produces a different spot pattern in the channel, so if the virus particle is labeled to respond to blue light, for example, it will light up nine times as it goes through the channel, if it’s labeled for red it lights up seven times, and so on,” Schmidt explained.

The researchers tested the device using three different influenza subtypes labeled with different fluorescent markers. Initially, each strain of the virus was labeled with a single dye color, and three wavelengths of light were used to detect them in a mixed sample. In a second test, one strain was labeled with a combination of the colors used to label the other two strains. Again, the detector could distinguish among the viruses based on the distinctive signals from each combination of markers. This combinatorial approach is important because it increases the number of different targets that can be detected with a given number of wavelengths of light.

For these tests, each viral subtype was separately labeled with fluorescent dye. For an actual diagnostic assay, fluorescently labeled antibodies could be used to selectively attach distinctive fluorescent markers to different strains of the flu virus.

While previous studies have shown the sensitivity of Schmidt’s optofluidic chips for detection of single molecules or particles, the demonstration of multiplexing adds another important feature for on-chip bioanalysis. Compact instruments based on the chip could provide a versatile tool for diagnostic assays targeting a variety of biological particles and molecular markers.

The optofluidic chip was fabricated by Schmidt’s collaborators at Brigham Young University led by Aaron Hawkins. The joint first authors of the PNAS paper are Damla Ozcelik and Joshua Parks, both graduate students in Schmidt’s lab at UC Santa Cruz. Other coauthors include Hong Cai and Joseph Parks at UC Santa Cruz and Thomas Wall and Matthew Stott at BYU.

In another recent paper, published September 25 in Nature Scientific Reports, Schmidt’s team reported the development of a hybrid device that integrates an optofluidic chip for virus detection with a microfluidic chip for sample preparation.

“These two papers represent important milestones for us. Our goal has always been to use this technology to analyze clinically relevant samples, and now we are doing it,” Schmidt said.

Boom in Gene-Editing Studies amid Ethics Debate over Its Use

Mon, 10/12/2015 – 1:54pmby Lauran Neergaard, AP Medical Writer

http://www.mdtmag.com/news/2015/10/boom-gene-editing-studies-amid-ethics-debate-over-its-use-0

The hottest tool in biology has scientists using words like revolutionary as they describe the long-term potential: wiping out certain mosquitoes that carry malaria, treating genetic diseases like sickle cell, preventing babies from inheriting a life-threatening disorder.

It may sound like sci-fi, but research into genome editing is booming. So is a debate about its boundaries, what’s safe and what’s ethical to try in the quest to fight disease.

Does the promise warrant experimenting with human embryos? Researchers in China already have, and they’re poised to in Britain.

Should we change people’s genes in a way that passes traits to future generations? Beyond medicine, what about the environmental effects if, say, altered mosquitoes escape before we know how to use them?

“We need to try to get the balance right,” said Jennifer Doudna, a biochemist at the University of California, Berkeley. She helped develop new gene-editing technology and hears from desperate families, but urges caution in how it’s eventually used in people.

The U.S. National Academies of Science, Engineering and Medicine will bring international scientists, ethicists and regulators together in December to start determining that balance. The biggest debate is whether it ever will be appropriate to alter human heredity by editing an embryo’s genes.

“This isn’t a conversation on a cloud,” but something that families battling devastating rare diseases may want, Dr. George Daley of Boston Children’s Hospital told specialists meeting this week to plan the ethics summit. “There will be a drive to move this forward.”

Laboratories worldwide are embracing a technology to precisely edit genes inside living cells — turning them off or on, repairing or modifying them — like a biological version of cut-and-paste software. Researchers are building stronger immune cells, fighting muscular dystrophy in mice and growing human-like organs in pigs for possible transplant. Biotech companies have raised millions to develop therapies for sickle cell disease and other disorders.

The technique has a wonky name — CRISPR-Cas9 — and a humble beginning.

Doudna was studying how bacteria recognize and disable viral invaders, using a protein she calls “a genetic scalpel” to slice DNA. That system turned out to be programmable, she reported in 2012, letting scientists target virtually any gene in many species using a tailored CRISPR recipe.

There are older methods to edit genes, including one that led to an experimental treatment for the AIDS virus, but the CRISPR technique is faster and cheaper and allows altering of multiple genes simultaneously.

“It’s transforming almost every aspect of biology right now,” said National Institutes of Health genomics specialist Shawn Burgess.

In this photo provided by UC Berkeley Public Affairs, taken June 20, 2014 Jennifer Doudna, right, and her lab manager, Kai Hong, work in her laboratory in Berkeley, Calif. The hottest tool in biology has scientists using words like revolutionary as they describe the long-term potential: wiping out certain mosquitoes that carry malaria, treating genetic diseases like sickle-cell, preventing babies from inheriting a life-threatening disorder. “We need to try to get the balance right,” said Doudna. She helped develop new gene-editing technology and hears from desperate families, but urges caution in how it’s eventually used in people. (Cailey Cotner/UC Berkeley via AP)

CRISPR’s biggest use has nothing to do with human embryos. Scientists are engineering animals with human-like disorders more easily than ever before, to learn to fix genes gone awry and test potential drugs.

Engineering rodents to harbor autism-related genes once took a year. It takes weeks with CRISPR, said bioengineer Feng Zhang of the Broad Institute at MIT and Harvard, who also helped develop and patented the CRISPR technique. (Doudna’s university is challenging the patent.)

A peek inside an NIH lab shows how it works. Researchers inject a CRISPR-guided molecule into microscopic mouse embryos, to cause a gene mutation that a doctor suspects of causing a patient’s mysterious disorder. The embryos will be implanted into female mice that wake up from the procedure in warm blankets to a treat of fresh oranges. How the resulting mouse babies fare will help determine the gene defect’s role.

Experts predict the first attempt to treat people will be for blood-related diseases such as sickle cell, caused by a single gene defect that’s easy to reach. The idea is to use CRISPR in a way similar to a bone marrow transplant, but to correct someone’s own blood-producing cells rather than implanting donated ones.

“It’s like a race. Will the research provide a cure while we’re still alive?” asked Robert Rosen of Chicago, who has one of a group of rare bone marrow abnormalities that can lead to leukemia or other life-threatening conditions. He co-founded the MPN Research Foundation, which has begun funding some CRISPR-related studies.

So why the controversy? CRISPR made headlines last spring when Chinese scientists reported the first-known attempt to edit human embryos, working with unusable fertility clinic leftovers. They aimed to correct a deadly disease-causing gene but it worked in only a few embryos and others developed unintended mutations, raising fears of fixing one disease only to cause another.

If ever deemed safe enough to try in pregnancy, that type of gene change could be passed on to later generations. Then there are questions about designer babies, altered for other reasons than preventing disease.

In the U.S., the NIH has said it won’t fund such research in human embryos.

In Britain, regulators are considering researchers’ request to gene-edit human embryos — in lab dishes only — for a very different reason, to study early development.

Medicine aside, another issue is environmental: altering insects or plants in a way that ensures they pass genetic changes through wild populations as they reproduce. These engineered “gene drives” are in very early stage research, too, but one day might be used to eliminate invasive plants, make it harder for mosquitoes to carry malaria or even spread a defect that gradually kills off the main malaria-carrying species, said Kevin Esvelt of Harvard’s Wyss Institute for Biologically Inspired Engineering.

No one knows how that might also affect habitats, Esvelt said. His team is calling for the public to weigh in and for scientists to take special precautions. For example, Esvelt said colleagues are researching a tropical mosquito species unlikely to survive cold Boston even if one escaped locked labs.

“There is no societal precedent whatsoever for a widely accessible and inexpensive technology capable of altering the shared environment,” Esvelt told a recent National Academy of Sciences hearing.

Researchers Use ‘Avatar’ Experiments to Get Leg Up On Locomotion

Mon, 10/12/2015 – 5:09pmby North Carolina State University

North Carolina State University scientists take a giant leap closer to understanding locomotion from the leg up

http://www.mdtmag.com/news/2015/10/researchers-use-avatar-experiments-get-leg-locomotion

Simple mechanical descriptions of the way people and animals walk, run, jump and hop liken whole leg behavior to a spring or pogo stick.

But until now, no one has mapped the body’s complex physiology – which in locomotion includes multiple leg muscle-tendons crossing the hip, knee and ankle joints, the weight of a body, and control signals from the brain – with the rather simple physics of spring-like limb behavior.

Using an “Avatar”-like bio-robotic motor system that integrates a real muscle and tendon along with a computer controlled nerve stimulator acting as the avatar’s spinal cord, North Carolina State University researchers have taken a giant leap closer to understanding locomotion from the leg up. The findings could help create robotic devices that begin to merge human and machine in order to assist human locomotion.

Despite the complicated physiology involved, NC State biomedical engineer Greg Sawicki and Temple University post-doctoral researcher Ben Robertson show that if you know the mass, the stiffness and the leverage of the ankle’s primary muscle-tendon unit, you can predict neural control strategies that will result in spring-like behavior.

“We tried to build locomotion from the bottom up by starting with a single muscle-tendon unit, the basic power source for locomotion in all things that move,” said Greg Sawicki, associate professor in the NC State and UNC-Chapel Hill Joint Department of Biomedical Engineering and co-author of a paper published in Proceedings of the National Academy of Sciences that describes the work. “We connected that muscle-tendon unit to a motor inside a custom robotic interface designed to simulate what the muscle-tendon unit ‘feels’ inside the leg, and then electrically stimulated the muscle to get contractions going on the benchtop.”

The researchers showed that resonance tuning is a likely mechanism behind springy leg behavior during locomotion. That is, the electrical system – in this case the body’s nervous system – drives the mechanical system – the leg’s muscle-tendon unit – at a frequency which provides maximum ‘bang for the buck’ in terms of efficient power output.

Sawicki likened resonance tuning to interacting with a slinky toy. “When you get it oscillating well, you hardly have to move your hand – it’s the timing of the interaction forces that matters.

“In locomotion, resonance comes from tuning the interaction between the nervous system and the leg so they work together,” Sawicki said. “It turns out that if I know the mass, leverage and stiffness of a muscle-tendon unit, I can tell you exactly how often I should stimulate it to get resonance in the form of spring-like, elastic behavior.”

The findings have design implications relevant to designing exoskeletons for able-bodied individuals, as well as exoskeleton or prosthetic systems for people with mobility impairments.

“In the end, we found that the same simple underlying principles that govern resonance in simple mechanical systems also apply to these extraordinarily complicated physiological systems,” said Robertson, the corresponding author of the paper.

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