Diagnostics Archive

Monday, September 28, 2009

Using the Xbox 360 for Cardiac Research

Microsoft Xbox 360 not only can stimulate your mind, but it also is now being used to investigate cardiac abnormalities.

Dr. Simon Scarle, a University of Warwick researcher, has detailed his work in using the Graphical Processing Unit (GPU) of an Xbox 360 to model and simulate cardiac arrhythmia in the hopes of understanding their initiation and propagation, so as to develop better treatments. While computer modeling has been around for decades, the breakthrough in this work is using a faster, cheaper, and commercially mass produced computer to accurately model the complex cardiac electrical system. Normally this type of modeling is constrained to supercomputers and must compete for computational time with a whole host of other important scientific modeling applications.

Snapshot of the graphical image display showing the outward action potential passing around a cardiac block and the return of the action potential. (Image from Scarle; 2009)

Scarle undertook this work while a software engineer at Microsoft's Rare Studio and modified the GPU to display tracking data of how electrical signals in the heart move around damaged cardiac cells. This creates a visual model of tissue to allow clinicians to identify cardiac conditions such as arrhythmia.

"These game consoles aren't just glorified toys. [They] are pieces of very powerful computing hardware," Scarle says. "I can see this ... being most useful for students and early-career scientists to just quickly and cheaply grab that extra bit of computing power they otherwise wouldn't be able to get."

Scarle developed this project as a fusion of his background as a software engineer in gaming and his past experiences with performing electrocardio-dynamics research at the University of Sheffield. He says that the idea for this heart-modeling project came from a "little shooter game" he developed while at Microsoft in which the player would gun down enemies in an arena that resembled a heart.

Now, if you will excuse us, we will be getting back to our ground breaking cancer research by playing HALO...

University of Warwick press release: Researchers using parallel processing computing could save thousands by using an Xbox...

Time : How Xbox Can Help Fight Heart Disease...

Microsoft Research : Implications of the Turing Completeness of Reaction-Diffusion Models, informed by GPGPU simulations on an XBox 360: Cardiac Arrhythmias, Re-entry and the Halting Problem...

Flashback : Dr. Halo: XBox Based "Care Consoles" to Invade Hospitals

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Tuesday, July 21, 2009

MicroEye Real Time Blood Monitoring System

The Engineer Online reports on Probe Scientific, a firm out of Bedford, UK, that has developed a continuous blood composition monitoring device that doesn't draw blood from the patient. The MicroEye system connects via most venous catheters and is already approved in Europe.

From the product page:

The MicroEye is intended for intravenous use for periods of up to 48 hours and is inserted via an 18G blood catheter. The range of substances that can be monitored using the MicroEye is vast including:
Electrolytes (such as potassium, magnesium etc.)

Energy metabolites (e.g. glucose, lactate, pyruvate, etc.)

Amino acids (glutamate, GABA, etc.)

Hormones and neurotransmitters (such as dopamine, serotonin (5-HT) etc.)

Inflammatory mediators and growth factors (e.g. cytokines, etc.)

Drugs and their metabolites (unbound 'free' fraction and / or total)

Product page: MicroEye...

(hat tip: The Engineer Online)

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Monday, July 13, 2009

Inkjet Printer Recruited to Print Toxin Detecting Paper Biosensors

Scientists at McMaster University have come up with a new methodology to create cheap biosensors using an inkjet printer. By applying a "lateral flow" sensing paradigm commonly seen in pregnancy test strips, the developers showed how one can implement a FujiFilm Dimatix Materials Printer to create sensors that can detect the presence of toxins, specifically acetylcholinesterase (AChE) inhibitors such as paraoxon and aflatoxin B1.

From a statement by McMaster:

The process involves formulating an ink like the one found in computer printer cartridges but with special additives to make the ink biocompatible. An ink comprised of biocompatible silica nanoparticles is first deposited on paper, followed by a second ink containing the enzyme, and the resulting bio-ink forms a thin film of enzyme that is entrapped in the silica on paper. When the enzyme is exposed to a toxin, reporter molecules in the ink change colour in a manner that is dependent on the concentration of the toxin in the sample.
This simple and cost-effective method of adhering biochemical reagents to paper is expected to bring the concept of bioactive paper a significant step closer to commercialization. The goal for bioactive paper is to provide a rapid, portable, disposable and inexpensive way of detecting harmful substances, including toxins, pathogens and viruses, without the need for sophisticated instrumentation. The research showed that the printed enzyme retains full activity for at least two months when stored properly, suggesting that such sensor strips should have a good shelf life.

Portable bio-sensing papers are expected to be extremely useful in monitoring environmental and food-based toxins, as well as in remote settings in less industrialized countries where simple bioassays are essential for the first stages of detecting disease.

Press release: Toxin detection as close as an inkjet printer ...

Abstract in Analytical Chemistry: Development of a Bioactive Paper Sensor for Detection of Neurotoxins Using Piezoelectric Inkjet Printing of Sol-Gel-Derived Bioinks ...

Image: This is topography of inkjet-sprayed PVAm, and AChE (50 U/mL) and DTNB doped sodium silicate (SS) thin films on paper. Credit: McMaster University

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Tuesday, June 23, 2009

Under Development: Micromagnetic-Microfluidic Blood Filter

The Ingber Lab at Harvard Medical School and Children's Hospital Boston has developed a magnetic blood filtering system to get rid of microbes from blood in situ. This system works by adding plastic-coated iron-oxide beads that are coated with antibodies for a specific pathogen. The beads will then strongly adhere to the pathogen in the blood and when passed through an electromagnet, the bead-pathogen complex can be separated from the rest of the blood. The end goal is to minimize the pathogen concentration to a level where drugs can be more effective at eliminating the remaining pathogen in the blood and reduce the mortality associated with sepsis.

In initial testing, the Ingber lab combined Candida albicans with blood and the antibody coated iron beads. The solution was then filtered through their system, a dialysis like device with electromagnets and up to 80 percent of the bead-pathogen complex were removed.

Image from Yung, C. W., et al, "Micromagnetic-microfluidic blood cleansing device" Lab Chip, 2009, 9, 1171-1177

This chart shows (a) the multi-fluorescence labeling of magnetic beads coated with antibodies for Candida albicans and (b) the effectiveness of the filtration of the bead-pathogen complex.

These types of microfluidic filter systems have the advantage of selective separation of the pathogen complexes from the flowing blood without the need for a filter membrane which can restrict flow and induce clotting while providing a large surface area to increase the efficiency of the entire prcoess. Dr. Don Ingber MD PhD, lab director, reports that animal testing is to commence this fall.

Popular Science : A Magnetic Machine Plucks Pathogens from Blood...

Lab Chip : Micromagnetic-microfluidic blood cleansing device...

Harvard Medical School and Children's Hospital : The Ingber Lab

Flashbacks: Sepsis Microfilter Being Developed ; Manipulating Cellular Signaling with Magnetic Fields

(hat tip: Gizmodo)

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Tuesday, April 28, 2009

Programmable Lab-On-A-Chip Devices Coming Soon

Lab-on-a-chip devices have the promise of delivering advanced diagnostics for all sorts of clinical and life science applications, bringing with them ease of use and potential reduction in costs. One major stumbling block of the technology is the production process of such devices, which requires that each lab-on-a-chip be designed specifically for every unique task. To overcome the problem, Purdue engineers have been working on a programmable lab-on-a-chip system that can become a ubiquitous multi-purpose product for a wide range of uses.

"With conventional technology, you have to design the individual layout of the chip, fabricate it, test it and then redesign it when testing uncovers problems," Wereley [Steven T. Wereley, associate professor of mechanical engineering at Purdue] said. "You are talking about a lot of time, effort and expense that could be dramatically reduced by having a multipurpose programmable chip."

For the life scientists who primarily use the technology, the devices are labor-intensive to develop and use.

"Imagine if running a word processing application on your computer required you to go to the lab and design your own microprocessor for that specific application," Amin [doctoral student Ahmed Amin] said. "Instead, wouldn't it be better if you could just buy a multipurpose chip and download the software you needed? That's what we're going to do -- make it easier to use so that the life scientists using the chips can concentrate on their own work instead of chip design."

Researchers at the Massachusetts Institute of Technology first suggested the idea of applying computer programming concepts to lab-on-a-chip technology in 2004.

"They have focused on programming-language aspects, while we're taking the idea to realization by focusing on the hardware and the software-hardware interface," Amin said. "We have developed the software compiler and the runtime system that would automatically understand a program and convert it into signals to control more complex chips."

The new chip is made out of a rubber-like polymer, called polydimethylsiloxane, instead of the rigid glass or silicon wafers often used. The flexible material is needed because pumps used to direct the flow of fluid operate with moving diaphragms.

Most other chips have the polymer layer sandwiched between two glass layers.

"We chose to build the whole chip out of the PDMS polymer, which makes it easier to fabricate and reduces cost over other alternatives, such as silicon or glass," Chuang [doctoral student Han-Sheng Chuang] said.

The Purdue-designed chip is able to mix, store, heat and sense what the sample is made of, whereas previous programmable chips have been limited to mixing and storing samples.

The researchers have demonstrated how the chip works using a mock sample and reagent dyed with food coloring.

The programmable chips are likely to be commercially available within five years, said Amin, a student in the School of Electrical and Computer Engineering who developed the programming language and "architecture," or interface between the hardware and software.

The language enables the "assay protocols" required for specific tasks to be downloaded to the chip.

Purdue has applied for a provisional patent on the technology.

"What we eventually aim to do is create different classes of chips, where each class can run multiple assays from a few related life-science domains," Amin said.

Press release: Innovation could make lab-on-a-chip devices easier to use, cheaper to make ...

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Wednesday, January 28, 2009

Dry Reagents Lead to Better Infectious Disease Tests for Developing World

Delivering on-site diagnostic tests for common diseases is a serious problem in the developing world. Reagents used in today's tests for diseases like malaria and typhoid are typically liquid and require refrigeration. Now researchers at the University of Washington have created a method to dry reagents in a malaria assay for easy transportation anywhere.

From University of Washington:

Results showed that malaria antibodies dried in sugar matrices retained 80 percent to 96 percent of their activity after 60 days of storage at elevated temperatures.
The goal of the long-term project is to develop a system with which a clinician can spot a drop of a patient's blood onto a card and feed it into an instrument that gives a yes/no answer for a panel of infectious diseases in 20 minutes or less. Tests with the prototype malaria card reached a result in less than nine minutes using an immunoassay, or antibody-based, approach.

The malaria-test card is being developed as part of an automated diagnostic system informally called the DxBox, the Dx being medical shorthand for diagnosis. The DxBox team is led by Yager and includes UW bioengineering professor Patrick Stayton; collaborators at PATH, a Seattle-based nonprofit focused on global health; Micronics Inc. of Redmond, Wash.; and Nanogen Inc. of San Diego.

The DxBox consists of a portable, fully automatic reader being developed by Micronics that will process the card-based disposable tests. The UW prototype cards look for the presence of malarial proteins, but the team is also working on other kinds of protein tests as well as a second kind of test for each disease that looks for the pathogen's DNA or RNA.

The UW's malaria cards use features of common lab tests and take into account portability, automation and easy storage. The cards rely on microfluidics, the manipulation of liquids at very small scales. Thin channels crisscross the Mylar sheets, and syringes are used to pump different liquids for the tests through the channels. "It's like plumbing, only the pipes are less than a millimeter wide," Yager said.

Microfluidics not only save space and resources, but working with liquids on such a small scale allows the researchers to do more. "It's not just about making big things small," Yager said. "It's also about doing things that are only possible at that very small scale." The diagnostic tests in the DxBox system run much faster than conventional tests in part because the liquids involved behave differently, a key factor for clinicians who have limited time to spend with their patients.

Currently, the researchers look for colored spots on the card that indicate the presence of malaria proteins. The hue of the color indicates the intensity of the disease. The DxBox can read these small spots automatically, reducing the chance for human error.

While the prototype developed by the UW researchers only tests for malaria, Yager and his collaborators are working towards cards that also will test for five other diseases that, like malaria, cause high-fever symptoms: dengue, influenza, Rickettsial diseases, typhoid and measles.

Press release: 'Astronaut food approach' to medical testing: Dehydrated, wallet-sized malaria tests promise better diagnoses in developing world

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Monday, January 26, 2009

Coming Up: Injectable Under Skin Glucose Sensors

Scientists at Draper Laboratory, a research company out of Cambridge, Massachusetts, are developing an injectable nanomaterial that fluoresces under infrared light in the presence of predetermined amounts of glucose. The idea is to make something like a tattoo that can provide constant monitoring for diabetics. So far, investigators at Draper have developed a version that can detect sodium, and are now working to transfer the technology to glucose.

MIT Technology Review reports:

The material consists of 120-nanometer polymer beads coated with a biocompatible material. Within each bead is a fluorescent dye and specialized sensor molecules, designed to detect specific chemicals, such as sodium or glucose.
When injected into the skin, the sensor molecule pulls the target chemical--say, sodium--into the polymer from the interstitial fluid, which surrounds cells. To compensate for the newly acquired positive charge of a sodium ion, a dye molecule releases a positive ion, making the molecule fluoresce. The level of fluorescence increases with the concentration of the chemical target. Scientists can swap in different recognition molecules to measure different targets, including chloride, calcium, and glucose. The range of concentrations that the sensor can detect can be varied by altering the ratio of the components, depending on whether it is important to measure precise concentrations or more broad variability.

The sodium sensor, which could one day be used to monitor dehydration, has shown early success in animals. When injected into rodents' skin, the beads stay put and fluoresce in response to saline injections. The researchers have developed a glucose sensor that works via a similar mechanism. It has been shown to work in a solution but has not yet been tested in animals.

Video of cells injected with the new material fluorescing in the presence of sodium:

Monday, December 22, 2008

New Technology Promises Compact High-Intensity Therapeutic Ultrasound

A Cornell graduate student in biomedical engineering has overcome one of the problems that has kept ultrasound devices large and bulky. By building a transducer that almost doubles in efficiency, George K. Lewis and adviser William L. Olbricht were able to build a pocket-sized high-intensity therapeutic ultrasound. The researchers hope that their new technology, now undergoing animal trials, one day will make it into portable clinical devices that could "stabilize a gunshot wound or deliver drugs to brain cancer patients."

Tinkering in his Olin Hall lab, George K. Lewis, a third-year Ph.D. student in biomedical engineering and a National Science Foundation fellow, creates ultrasound devices that are smaller, more powerful and many times less expensive than today's models. Devices today can weigh 30 pounds and cost $20,000; his is pocket-sized and built with $100. He envisions a world where therapeutic ultrasound machines are found in every hospital and medical research lab.
Lewis suggests that his technology could lead to such innovations as cell phone-size devices that military medics could carry to cauterize bleeding wounds, or dental machines to enable the body to instantly absorb locally injected anesthetic.

Lewis miniaturized the ultrasound device by increasing its efficiency. Traditional devices apply 500-volt signals across a transducer to convert the voltage to sound waves, but in the process, about half the energy is lost. In the laboratory, Lewis has devised a way to transfer 95 percent of the source energy to the transducer.

His new devices are currently being tested in a clinical setting at Weill Cornell Medical College. Under the direction of Jason Spector, M.D, director of Weill Cornell's Laboratory for Bioregenerative Medicine and Surgery and assistant professor of plastic surgery, Peter Henderson, M.D., the lab's chief research fellow, is using one of the devices in experiments that aim to minimize injury that occurs when tissues do not receive adequate blood flow.

Their lab is performing tests in animals to determine whether low doses of the chemical hydrogen sulfide, known to be toxic at high doses, might be able to minimize such injury by slowing cellular metabolism.

Doctors are hopeful that the ultrasound from Lewis' portable device will enable hydrogen sulfide to be targeted to specific parts of the body, allowing doctors to use less of it, and cutting down on toxicity risks, Henderson explained.

From the article abstract in Review of Scientific Instruments:

We have developed a portable high power ultrasound system with a very low output impedance amplifier circuit (less than 0.3 Omega) that can transfer more than 90% of the energy from a battery supply to the ultrasound transducer. The system can deliver therapeutic acoustical energy waves at lower voltages than those in conventional ultrasound systems because energy losses owing to a mismatched impedance are eliminated. The system can produce acoustic power outputs over the therapeutic range (greater then 50 W) from a PZT-4, 1.54 MHz, and 0.75 in diameter piezoelectric ceramic. It is lightweight, portable, and powered by a rechargeable battery. The portable therapeutic ultrasound unit has the potential to replace “plug-in” medical systems and rf amplifiers used in research. The system is capable of field service on its internal battery, making it especially useful for military, ambulatory, and remote medical application

Abstract in Review of Scientific Instruments...

Cornell press release: Grad student develops pocket-size, inexpensive ultrasound device...

Images: Top: George K. Lewis with his newest portable ultrasound device. Bottom: Ultrasound waves created by one of Lewis' devices leave the transducer, submerged under water, causing the water to bubble, spray and turn into steam.

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Monday, December 8, 2008

Bio-Seeq System IDs Microbes with LATE-PCR

Smiths Detection, part of Smiths Group, plc, is developing a portable pathogen identification system based on technology called LATE PCR (Linear After The Exponential Polymerase Chain Reaction).

From The Engineer Online:

It is based on a special type of polymerised chain reaction, a process for analysing nucleic acids and DNA. The version Smiths uses amplifies just one side of the DNA double helix, producing a single-strand product. This has significant advantages, principally that it can easily have parallel tests carried out so more characteristics can be examined.
The platform comes in three parts. The main instrument that carries out the analysis sits on a desk. A consumable called a sample preparation unit (SPU) receives any sample type using a universal preparation method. The third component is an assay-specific reagent pack, which contains the various chemicals to detect the specific organism.

'The user takes an SPU, adds the reagents to turn it into a specific assay, puts the lid down to seal the sample in, then places it on the machine which can read a unique barcode and automatically carry out the analysis,' said Lewington. The barcode contains all the information about the sample, the method of how to run the test, and the analytical procedure to carry out.

Friday, December 5, 2008

Chip-on-a-Pill, and Other Micro-Electro-Medical Devices

Proteus Biomedical, a biomedical technology company out of Redwood City, California, has been selected as one of this year's World Technology Forum's Technology Pioneers. The company develops MEMS (microfabricated, multicomponent electronic components) devices for medical applications, small enough to be attached to pills to be used as "ingestible event markers", as well as potential permanently embedded blood glucose monitoring chips. Back in March, we had a post about this company's technology.

A statement by the company:

"Proteus has developed a unique approach to personalizing therapy," said Andrew Thompson, Proteus CEO and co-founder. "We embed micro-sensors into existing drugs and devices, which transmit information, securely, to a person’s cell phone via the Internet. A person can understand how their body is responding to their therapy, and, if they choose, share this information with a family member, physician or friend to help them stay healthy. We are delighted that the World Economic Forum has recognized the immense potential of this approach and look forward to actively participating in their programs."

Check out this video interview with Andrew Thompson:

Proteus Biomedical, Inc. ...

Press release: Proteus Biomedical Honored by World Economic Forum ...

More from SFgate.com: 5 Bay Area firms named 2009 Technology Pioneers...

Flashback: NextGen Pharmaceuticals: Pills That Talk, Sensors That Listen

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Wednesday, December 3, 2008

Zonare Shows Off Proprietary Ultrasound Technology

At the RSNA 2008 conference this week, ZONARE Medical Systems out of Mountain View, California is showing off its latest ultrasound transducers and image processing software for improved image quality. The company describes its z.one ultrasound system as "smaller, lighter, more maneuverable, and nimbler than any system of equivalent image quality."

From the press release:

New Transducer Technology The C4-1 is a small footprint, curved array transducer designed by ZONARE's acoustic engineers. It offers physicians improved access and imaging performance resulting in improved penetration with sensitive Doppler imaging. All ZONARE customers worldwide have access to this new technology on their current z.one ultrasound platform.
ZONARE is also showing its new L14-5w high resolution, high frequency transducer, which offers broad bandwidth for improved imaging of small parts, breasts and superficial anatomy. Its wide field of view has an aperture of 55mm offering virtual apex capability, and it has 10 frequencies including three fundamental, one tissue harmonic, two compound imaging and two each for color Doppler and PW Doppler modes.

Elastography and 3D Imaging
The z.one ultrasound system will feature new elastography applications that enable qualitative visual assessment of the mechanical stiffness properties of tissue. The high resolution elastography images are generated and visualized using a variety of grayscale and colorized maps and the L10-5 and L14-5w transducers are supported. Clinicians using the new applications report that this technique may provide significant new diagnostic information.
The comprehensive 3D ultrasound imaging capabilities are available for the z.one ultra system with primary applications for obstetrical imaging during the second and third trimester. The new C8-33D curved linear transducer offers mechanical sweep array, 3D fetal surface rendering, 3D Multi Planar rendering and additional diagnostic tools. The new 3D imaging capabilities are also available for general abdominal ultrasound imaging. ZONARE's 3D ultrasound imaging expands the clinical utility of the z.one ultra system and may reduce exam time, enabling physicians to spend additional time on patient care.

Proprietary Software
The difficult-to-image patient population makes up a large percentage of patients examined with ultrasound today and includes people who are overweight, elderly, muscular, or who have a thick body wall. Traditionally, a definitive ultrasound diagnosis for this patient group was challenging and often these patients were referred for more expensive testing. ZONARE has engineered new proprietary software for ZONE Sonography technology and, when combined with the company's new C4-1 transducer, clinicians have a new tool to image their most technically difficult patients with advanced image clarity.

Press release: ZONARE Medical Systems Introduces Advancements for z.one Ultrasound Platform at RSNA ...

Product page: z.one Ultrasound Platform ...

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Monday, December 1, 2008

Nano Technology Helps Detect Lung Cancer in Breath

Dr. Hossam Haick and colleagues from the Israel Institute of Technology have published an article in Nano Letters describing their technology for detecting lung cancer markers in human breath.

From the National Cancer Institute:

Dr. Haick and his collaborators first created individual devices consisting of random networks of single-walled carbon nanotubes coated with 1 of 10 different insulating nonpolymeric organic materials. The investigators used standard microprocessor fabrication techniques to create the sensors. Thanks to the different organic materials used to coat the nanotubes, each sensing device provided a unique response when exposed to wide variety of the more than 200 volatile organic chemicals present in human breath.
To calibrate the devices, the investigators captured the breath of 15 nonsmoking healthy patients and 15 individuals with stage 4 lung cancer. Next, they concentrated the organic compounds in each breath sample using a method known as solid phase microextraction and then analyzed each sample using gas chromatography-mass spectrometry (GC-MS). GC-MS is a highly accurate technique that is too expensive and time consuming to find use as a routine diagnostic assay. The researchers then ran the same samples through their sensor array; the electrical output of the test devices changed in a way that was characteristic of the exact mixture of organic compounds found in the breath samples.

From these data, the investigators were able to distinguish between two response patterns from each of the 10 array members. There was no overlap in the response patterns between the healthy and lung cancer patients in these first tests. The researchers are now testing their system on a much larger group of patients and healthy subjects.

Press release: Carbon Nanotubes Detect Lung Cancer Markers in the Breath ...

Abstract: Detecting Simulated Patterns of Lung Cancer Biomarkers by Random Network of Single-Walled Carbon Nanotubes Coated with Nonpolymeric Organic Materials

Image: Lung cancer cells. Wellcome Images.

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Tuesday, November 25, 2008

Magnotech Point of Care Lab Testing

Philips has developed new lab-on-chip technology, dubbed Magnotech, that utilizes magnetic nanoparticles that the company believes can lead to bedside immunoassay results as good as from the lab.

From Philips:

Integrated into a disposable biosensor cartridge that inserts into a hand-held analyzer, Magnotech uses magnetic nanoparticles to measure target molecules in very low (picomolar) concentrations in blood or saliva - in just a few minutes. The disposable cartridge automatically fills itself from a single drop of blood or saliva. Once filled, no other fluid movement is required. Currently, measuring very low concentrations of biomarkers for the diagnosis of disease (for example, cardiovascular disease) requires laboratory analysis, large sample volumes and a time-to-result delay of between 30 and 60 minutes.
The Philips' Magnotech handheld technology has the potential to deliver:

Small sample volume (fingerpick drop of blood or saliva)

Ease of use (potentially applicable for home testing)

Multi-analyte (several analytes can be measured simultaneously, depending on the application)

Lab-quality sensitivity

Speed (measurement in 1-5 minutes depending on the application)

The underlying technology

The magnetic nanoparticles are preloaded into the cartridge during its manufacture and automatically disperse into the sample as the cartridge fills with saliva or blood. Coated with appropriate ligand molecules, the nanoparticles quickly bind to target molecules in the fluid sample.

An electromagnet situated under the cartridge brings the magnetic nanoparticles, including the captured target molecules, into contact with the active detection surface of the biosensor in order to achieve fast specific binding at this active surface. A second magnetic field then pulls any unbound magnetic nanoparticles away from the active surface, enabling measurement of the remaining target molecules. The measurement is done using an optical technique based on frustrated total internal reflection.

Philips has demonstrated proof-of-concept for its new biosensor technology in a variety of biological assays, including sandwich assays for the detection of cardiac Troponin I (cTnI)[2] and parathyroid hormone (PTH)[1], and inhibition assays to detect several drugs-of-abuse molecules (amongst others, morphine). Cardiac Troponin is a blood-borne protein that at elevated levels provides a useful biomarker for the diagnosis of myocardial infarction (heart attack). The morphine assay represents the first test of the technology in drugs-of-abuse testing.

During these proof-of-concept tests, Philips' Magnotech technology was shown to speed up assays by a factor of more than 100 when compared to simply letting the nanoparticles diffuse to the sensor's active surface. Furthermore, the technology improves ease of use by eliminating fluidic washing steps. With cTnI, the assay successfully detected minute (picomolar) concentrations in under five minutes.

Press release: Philips breakthrough Magnotech technology set to transform global point-of-care testing...

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Monday, November 17, 2008

Identifying Protein Presence Quickly and Cheaply

A microfluidic chip that uses a novel technology to identify the presence of circulating proteins in a minuscule blood sample may lead to a new generation of quick and accurate diagnostic tests. The chip's technology is being developed by Caltech professor of chemistry Dr. James Heath and by Dr. Leroy Hood, the founder of the Institute for Systems Biology, in Seattle.

MIT Technology Review explains:

Heath and Hood's device, described in this week's issue of Nature Biotechnology, starts the analysis process with some simple microfluidics. A drop of blood is pulled down a microscale channel by the application of a small external pressure. This first channel branches off into narrower ones, which exclude blood cells and admit the protein-rich blood serum. In typical blood tests, this separation step requires a centrifuge.
The narrower channels are patterned with what Heath calls a protein bar code--lines of DNA bound to antibodies that capture proteins of interest from the serum. After the serum and cells are flushed out, antibodies bound to red fluorescent proteins are flushed in, lighting up captured blood proteins. The protein bar codes can be read under a fluorescent microscope or a gene-chip scanner. The identity of the captured blood proteins can be determined by the location of red lines in the bar code relative to a green fluorescent reference line.

By measuring how much light radiates from a particular protein's spot in the bar code, Heath and Hood can quantify its concentration in the blood. Heath notes that the chip can measure blood proteins present over a wide concentration range, making it possible to measure not only plentiful blood proteins created by the immune system, but also rarer proteins originating in organs such as the brain. The device is as sensitive as conventional protein tests, and Heath and Hood can measure any proteins they're interested in by making custom chips with the right antibodies.

Friday, November 14, 2008

Optical Tweezers to Pick Out Pathogens from Blood Samples

The National Institute of Standards and Technology has licensed its optical tweezer technology to Haemonetics out of Braintree, Massachusetts to develop it into a practical method of performing highly sensitive blood tests.

Optical tweezers are actually tightly focused laser beams. They can trap certain objects, such as latex microspheres or biological cells, and move them around in water. This occurs because the lasers' electric fields interact with electric charges on the objects.
To detect disease-causing agents, researchers can coat a microsphere with antibody particles and then touch it to a surface containing infectious particles (antigens). The antigens then stick to the antibodies on the sphere, reminiscent of Velcro, in which loops on one strip combine with hooks on the other. By determining how much laser power is required to pull the microsphere away from the surface, one can then calculate the amount of force needed to break off the antibodies from the antigens and thus count the number of individual antigens that were bound to the sphere. This in turn can detect and count biological antigens at extraordinarily low “femtomolar” concentrations—roughly equivalent to one antigen particle per quadrillion (1,000,000,000,000,000) water molecules.

Full story: 'Femtomolar Optical Tweezers' May Enable Sensitive Blood Tests ...

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Monday, November 3, 2008

Project to Develop Wearable Battlefield "Hospital"

A team at the University of California San Diego has received a grant from the U.S. Office of Naval Research to develop a "hospital-on-a-chip" system that will, in the far off distant future, have a wearable device to sense the body's biochemical changes, which will then be linked through a computer controller to a unit that can administer medicine based on the sensor's findings. Hopefully one day this technology will provide initial treatment to soldiers wounded in the field, and may very well find itself in commercial applications such automated systems for diabetics.

To realize their “field hospital on a chip” idea, the engineers will need to build a minimally invasive system that monitors multiple biomarkers simultaneously and uses the system’s “smarts” to process all this biomarker information and tease out accurate, automated diagnoses. These diagnoses would immediately trigger drug delivery or other medical intervention.
“Today’s insulin and glucose management systems for patients with diabetes don’t include smart sensors capable of performing complex logic operations,” said Wang, who helped to develop the first noninvasive system for monitoring glucose from a patient’s sweat. “We are working on a system that will be different. It will monitor biomarkers and make decisions about the type of injury a person has sustained and then begin treating that person accordingly,” said Wang.

To reach this level of automated diagnostic dexterity, the researchers plan to build upon “enzyme logic” breakthroughs recently demonstrated by Evgeny Katz, a Co-PI on the grant and the Milton Kerker Chaired professor of Chemistry and Biomolecular Science at Clarkson University.

Katz and colleagues demonstrated recently that enzymes can not only measure biomarkers, but also provide the logic necessary to make a limited set of diagnoses based on multiple biological variables.

Lactate, oxygen, norepinephrine and glucose are examples as the kinds of injury biomarkers that will serve as biological input signals for their prototype logic system. Electrodes containing a combination of enzymes will serve as sensors and provide the logic necessary to convert the biomarkers to products which may then be picked up by another enzyme on the electrode for further logic operations. The electrodes will also act as transducers that produce strings of 1s and 0s that will activate smart materials that release medication based on predetermined treatment plans.

“We just want the ones and zeros. The pattern of ones and zeros will reveal the type of injury and automatically trigger the proper treatment,” said Wang.

For example, if an injured soldier were to enter a state of shock, enzymes on the electrode would sense rising levels of the biomarkers lactate, glucose and norepinephrine. In turn, the concentrations of products generated by the enzymes would change—higher hydrogen peroxide, lower norepi-quinone, higher NADH and lower NAD+. This will cause the built-in logic structure to output the signal “1,0,1,0” which points to shock and will trigger a pre-determined treatment response.

Read: Field-Hospital-on-a-Chip Project Awarded to NanoEngineer from UC San Diego...

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Friday, October 24, 2008

Continuous MicroCHIPS Glucose Monitoring Shows Promise

Popular Science is reporting on the work of MicroCHIPS, a Bedford, Massachusetts firm that's designing under-skin implantable devices to measure chemicals and deliver drugs. The exciting news is that the firm will be performing clinical trials next year on its glucose detecting microchip, a device that has apparently shown positive results when studied on animals.

From the company technology page:

MicroCHIPS' technology is based on proprietary reservoir arrays that are used to store and protect chemical sensors or potent drugs within the body for long periods of time. These arrays are designed for compatibility with preprogrammed microprocessors, wireless telemetry, or sensor feedback loops to provide active control. Individual device reservoirs can be opened on demand or on a predetermined schedule to precisely control drug release or sensor activation.
Our reservoir-based platform can also be used in passive control systems without microprocessors or power sources. MicroCHIPS' passive systems are designed to release or expose their contents based on the controlled degradation of polymeric matrices over time. These systems form the basis for miniature insertable devices that provide maximum flexibility for device placement.

Thursday, October 23, 2008

Tomophase OCT System and the Future of Pulmonary Diagnostics

Optical Coherence Tomography (OCT), like Star Trek's USS Enterprise, is setting its sights to boldly go where no medical gadget has gone before. We've followed this technology's journey through the retinal layers, coronary arterial plaque layers, and other tissues at the sub-micrometer level. OCT is able to achieve incredibly detailed images by collecting near infrared (NIR) light reflected back from tissue structures, much like an ultrasound relies on reflected ultrasonic waves. Because the frequency of NIR light is orders of magnitude smaller than that of ultrasound waves, resolving power is greatly amplified but depth of penetration is greatly reduced (but U/S level of depth penetration is not required to image sub-cellular details).

Now, Tomophase Corp. of Burlington Mass., is ready to take OCT to distant pulmonary recesses in the lung. Presenting at the CHEST meeting in Philadelphia, Oct. 27th through Oct. 29th, Tomophase will demonstrate their Investigational Airway & Pulmonary Tissue Imaging Systems, which consists of a flexible catheter that inserts through the working channel of a bronchoscope.

From the press release:

"Our goal at Tomophase is to use our proprietary optical technology to help clinicians image subsurface pulmonary tissue at a level of resolution currently unavailable, while not exposing the patient to potentially harmful radiation, UV light or contrast agents," commented Dr. Peter Norris, CEO of Tomophase. "Much of the structure in the airways beneath the epithelial layer is essentially invisible to clinicians. Providing real-time access to this information could provide major benefits to both diagnostic and therapeutic approaches to many pulmonary diseases. We believe this research collaboration with Beth Israel Deaconess is an important first step in establishing the utility of this breakthrough technology in both research and the clinic."
The Tomophase system is designed to enable the high-resolution visualization of bronchial and pulmonary tissue cross-sections without biopsy. Its design features include:

Subsurface Microanatomy Visualization (within 2-3 mm)

Real-Time Operation

Micron Scale Resolution

Superior Image Clarity to other OCT Technologies

No Radiation, UV light or Contrast Agents

Sample Site Morphology Information Retained

Both Forward and Side Scan Imaging (in development)

Tissue Metabolic/Biochemical Information (in development)

Press release: Tomophase To Exhibit First Cross-Sectional Images Of Human Bronchus Using Proprietary OCT System...

Tomophase technology page...

Bottom image from Tomophase website: Normal human pulmonary tissue; field of view 1.5 mm x 4 mm.

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DARPA Nose Competition

DARPA (Defence Advanced Research Projects Agency) is sponsoring a new competition to develop "... a highly versatile and sensitive broad-spectrum device capable of detecting odorants under the challenge of real-world conditions". Obviously the military and security implications are immense, but so is the potential to develop further knowledge about the inner workings of one of the most primitive CNS pathways.

Like the X-Prize devoted to Healthcare we reported on earlier, DARPA's projects attract some of the top scientists from around the world and leverages their knowledge and inspiration to produce exponential gains in the field.

Evolved Machines, Inc. (Palo Alto, CA) has been selected as a prime contractor to engineer an artificial olfaction system incorporating "brain-like" neural pattern recognition. In their press release, DARPA labeled the project "RealNose", and the agency emphasizes that it will be "the first program to tackle the separation of multiple odorants in the presence of unknown backgrounds that characterize the detection problems presented in real-world settings."

As with so many advances in medicine which evolved from military initiatives, the potential for medical gain goes beyond just the increased knowledge of neural networks, it could provide "simplified" detectors for cancers, infectious diseases, diabetes, and many other illnesses shown to be detectable by canines (among other animals).

Darpa Press Release at SAIC...

Evolved Machines Website

MIT News Release: Sniffing Out Success...

Flashbacks: No, Not Another Electronic Nose! ; Nanowire-based Electronic Nose; E-nose to Detect Lung CA; SPOT-NOSED: A Hi-Tech Nose For Disease Detection; "Electronic Nose" to Aid Asthma Diagnosis; Detecting Infection With E-nose