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The disease detectors are composed of a nanoparticle metal core (orange), surrounded by a protective polymer (gray), with binding molecules attached to the surface (blue). These molecules bond to specific molecules on cancer cells, bacteria, or pollutants (green) in order to detect their presence.  (Source: T2 Biosystems)
New scanner provides cancer, diabetes, and bacterial detection in the palm of your hand; also useful for anti-terrorist efforts

Diabetics have convenient pin-prick hand-held testers to check their sugar levels.  What if a similar device could test for various viral, bacterial infections, and even skin or metastasized cancer cells?  That's exactly what American researchers at Harvard Medical School in Cambridge, Massachusetts, US intend.

The researchers have developed a device that can only be sufficiently described as an incredible breakthrough.  It may soon revolutionize many aspects of disease diagnosis.

To understand the new device, it is important to grasp how it works.

Many who have suffered through (or enjoyed) an organic chemistry class are familiar with Nuclear Magnetic Resonance (NMR) imaging machines -- bulky lab machines designed to detect certain groups of chemicals.  It's hard to imagine an NMR scanner being held in the palm of your hand, but that's precisely how researchers are approaching the problem.

Nuclear magnetic resonance imaging works by exposing atoms' nuclei to magnetic fields and then pounding them with radio waves causing them to wobble.  This wobble induces currents in the detector coil, which vary by molecule, allowing the scanner to detect certain molecular structures.  While NMR scanners are typically found in chemistry labs, they're also commonplace in hospitals. Magnetic resonance imaging (MRI) machines use this phenomena to provide a non-invasive peek inside people's bodies.

The new handheld device is slightly different from a traditional MRI, in that it does not produce images.  Rather it provides detection of various molecules.  The process starts with the collection of a small fluid sample, typically blood.  The sample is collected using microfluidics network, which grabs samples of a mere five millionths of a liter (5 microliters) -- some 60 times less than conventional systems.

Hakho Lee, lead author of the research states, "The smaller the system, the better the sensitivity in terms of absolute amount of sample that can be detected."

The sample is then carried through a series of coils.  Inside each of these coils magnetic nanoparticles, bonded to special detector molecules are inserted.  The detector molecules are designed to bond to molecules on, say a specific bacteria, or a molecule on the surface of a cancer cell.  Each coil can feature its own separate detection check.

The magnetic nanoparticles make the whole system work, as they are sensitive even weak magnetic fields from the smaller magnets in a handheld sensor.  This allows for a miniaturized NRM, previously infeasible.  Ralph Weissleder of Harvard Med School and his colleagues devised the new method and squeezed the electronics for detection onto a chip measuring a mere 2 mm2.

The current prototype features 8 coils and is 800 times more sensitive than current full-sized medical lab NMRs.  In preliminary tests, scientists were able to identify samples of infectious bacteria with as few as 10 bacteria.  They plan to publish additional tests showing that the other 7 coils can be easily tasked with identifying cancer and diabetes (via blood sugar).

Mr. Lee says the device will revolutionize diagnosis.  He states, "The biggest advantage is that we don't need sample preparation or purification steps.  This method could provide an easy and fast way to diagnose almost any kind of disease, such as bacterial infection or cancers in point-of-care settings – right next to the patient or in developing countries."

The device could eventually also be used to analyze water, to aid in public safety or even to check gaseous samples for airborne pathogens or pollutants.  This could aid in antiterrorism devices by offering rapid detection of biological or chemical warfare agents.

The new research is generating a great deal of respect and excitement in the scientific community.  Remarks Dusan Uhrin, an NMR spectroscopist at the University of Edinburgh, "If you came to my lab you would see that our spectrometers occupy whole rooms, and we are always struggling with sensitivity in NMR experiments.  They have been able to improve the sensitivity such that they can detect just a few bacteria. It's quite remarkable that they can detect down to that limit"

The Harvard team hopes to quickly bring the new device to market.  Dr. Weissleder has applied for a patent.  He has also founded a new company named T2 Biosystems to market the product.

DailyTech spoke briefly with T2 Biosystems CEO John McDonough.  Mr. McDonough says the product is roughly two years from the mark and will be available in tabletop and handheld versions.  He says the key to the product is its ubiquitous nature in that it can test any liquid specimen for virtually anything, anywhere given the proper chemicals.

He states, "T2 is utilizing the science and technology of our founders to develop rapid, accurate and portable diagnostics for nearly any health condition, in nearly any setting. In addition to our advantages of speed to result and ease of use, our miniaturized instrument can accurately identify almost any analyte, including proteins, nucleic acids, or enzymes; bacterial, cancer or other cells; viruses; or small molecule drug compounds within almost any sample, including whole blood, plasma, serum and urine."

If T2 can succeed in this ambitious goal, the future certainly seems bright for this exciting new technology.

 



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Gene Roddenberry would be proud...
By MrBlastman on 7/10/2008 10:13:28 AM , Rating: 2
So the device works by using a series of coils - each coil featuring its own detection check; Does each detection check represent a single molecule or perhaps a class of molecules?

I think, what I'm trying to suggest that it seems each coil can be programmed and processed separately with their own function - is the sensitivity of each coil check (or nanoparticle for that matter) able to distinguish more than just a single target molecule and then categorize it within a set category.

Or, does the device require an individual coil for each and every molecule? I would err towards it being able to detect and sort within a class rather than one coil per molecule. My hats go off to the researchers - time is a very valuable commodity in the emergency room and anything they can do to speed up the detection of harmful conditions only buy the doctors more time to devise (and in this case more accurately) come up with a diagnosis and a solution.

The last thing does down to cleaning. To make it cost effective - you would want a device which could have the coils flushed after each procedure, or provide a device with inexpensive coils which can be swapped out after each patient to prevent cross-contamination and false-positives.




RE: Gene Roddenberry would be proud...
By zelachang on 7/10/2008 11:38:09 AM , Rating: 2
I would think it depends on the generality of the molecular bonding of each detector. For example, in the "bacteria coil" you could have a compound that binds to gram-positive bacteria and one that binds to gram-negative bacteria which would cover most types of bacteria. However, to reduce false positives, both of the detector molecules must be very specific for the cell surface of bacteria or else random other events could trigger a hit. Putting too many different detector molecule types in a coil could potentially cause the detector molecules to bond to each other as well. I think the situation would change for every class depending on the state of knowledge regarding detectors and the desired substrate.

The short answer is, I'm sure in most cases they have an array of different detectors designed to bind to a general class of substrates because these detectors are probably pretty specific.


RE: Gene Roddenberry would be proud...
By geddarkstorm on 7/10/2008 2:00:34 PM , Rating: 2
Most likely they use antibodies which are attached to the beads. That gives you incredible (up to femtomolar) sensitivity. Using a polyclonal antibody, you can target whole suites of molecules, such as those found only in the surface of bacteria like lipopolysaccharide A--you could then detect specific species of bacteria using antibodies specific to certain receptors or proteins only those species have. Really, this technology is applicable to way more than we can think up right here in one sitting.

Also, you wouldn't get the antibodies binding each other, but you don't want too many different antibodies in the same coil as then you lose specificity in your signal: can't tell if you are detecting only molecule A or molecule B in a coil that detects both.


RE: Gene Roddenberry would be proud...
By zelachang on 7/10/2008 4:06:30 PM , Rating: 2
I didn't even think about antibodies, I feel pretty stupid now since it makes so much sense. Are these beads bound to the antibodies you speak of the magnetic field inducing objects? The article seemed to imply that each antibody was attached to its own metal cofactor. I really wish there was a paper that explained the methods available for reading but I'm sure they don't want to divulge their potential moneymaker.


By zelachang on 7/10/2008 4:09:32 PM , Rating: 2
Edit:
I didn't see the picture above, answered my own question. Did see the reference to T2Biosystems and checked their website out. They don't mention antibodies specifically but they mentioned "multiple analyte-specific binding agents" which sounds pretty much like antibodies.


By Biodude on 7/10/2008 12:34:47 PM , Rating: 2
Man am I impressed with this machine. Before reading the journal article I though for sure that the connection with NMR was just an attempt at a rough description of what it does, but dang it if they haven't put a crude resonance detector on a micro scale. Crude is not a slam in this case - it's an elegant application of a crude system. High field strength NMR can be used to identify the structure of a complex compound, but this system doesn't have enough power to detect water if it wasn't for the "amplification" gained by the iron oxide beads.

Yes, each coil would be used to detect a single molecule. With the multiple coils available per test there would be little reason to combine tests to go for a class. If you think of this in terms of antibodies (which will be extensively used for many tests, although not for all) binding to molecules, and those antibodies (which are very specific in what they bind to) themselves stuck to the iron particles, then you have particles in each coil that specifically bind to only one thing.

I'm guessing with the microfluidic channels that it would be much easier, and more cost effective, to just fabricate one shot tests that can be used and tossed. If you want to use a test from one person to another you have to not only clean it well but be able to verify that it has been cleaned - think in terms of sterilizing surgical instruments. This thing is so small that I'm betting they will be made in bulk.

Very exciting!


By Carter642 on 7/10/2008 1:18:51 PM , Rating: 2
This is a seriously cool bit of tech. I'm a little confused though as to whether the nanoparticles are added to the sample i.e in the sample container prior to being placed in the coils with sample + particles seperated from the coils when it's scanning? Or are the particles somehow in with the coils?

I can just see going to the doctor and having a drop or two of blood taken rather than a vial. The tech adds in the nanoparticles for a standard blood panel, shakes it up and pops the tiny vial into the detector hole and a minute later the lab results pop up on screen.

As a bioinformaticist this is very exciting as it could bring about the advent of 'fast' dna matching as well as more precise sequencing. This really depends tho on whether this technology can detect relative concentrations of compounds. I'm still hopeful though.

House's going to be pissed tho cause then he can't banish his minions to the lab when he wants them out of his hair lol.


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