Weighing living cells

New MIT technique weighs single living cells.
For the first time, MIT researchers have found a way to measure the mass of single cells with high accuracy.

The new technique, which is based on a micromechanical detector, could allow researchers to develop inexpensive, portable diagnostic devices and might also offer a unique glimpse into how cells change as they undergo cell division.

Unlike conventional methods, the MIT technique allows cells to remain in fluid while they are being measured, opening up a new realm of possible applications, says Scott Manalis, senior author of a paper on the work that will appear in the April 26 issue of Nature.

In addition to weighing cells, the technology can be used to "weigh nanoparticles or sub-monolayers of biomolecules with a resolution in solution that is six orders of magnitude more sensitive than commercial mass sensor methods. One direction we're pursuing is mass-based flow cytometry, a way to weigh and count specific cells," said Manalis, an associate professor in MIT's Departments of Biological Engineering and Mechanical Engineering.

Current mass-measurement methods achieve a resolution down to a zeptogram (10 to the minus 21 grams) but only work with non-living things because the procedure must be performed inside a vacuum. So, the MIT researchers decided to turn the conventional system inside out.

In the traditional method, the molecules to be weighed are placed on top of a tiny slab, or cantilever, made of silicon. The slab vibrates at its resonant frequency (the frequency at which the material naturally tends to vibrate) inside a vacuum. When a molecule sits on the slab, the frequency changes slightly, and the mass of the molecule can be calculated by measuring that change.

This measurement must be performed in a vacuum to prevent air (or fluid) from interfering with the frequency of oscillation. However, cells cannot survive in a vacuum, so they must be measured in fluid, which diminishes the accuracy of the measurement.

The researchers solved this dilemma by placing the fluid containing the sample inside the silicon slab, which still oscillates within a vacuum surrounding it. The biological sample is pumped through a microchannel that runs across the slab, without impairing its ability to vibrate.

"The resonator is sealed in a tiny vacuum cavity inside the chip, so there is virtually no resistance to the vibration," said co-lead author Thomas Burg, a research associate in biological engineering. "This lets us measure a mass change, say 10 parts in a billion, of the already very light microcantilever."

So far, the researchers have weighed particles with a resolution down to slightly below a femtogram (10 to the minus 15 grams), but Manalis believes that with refinements, the sensitivity could potentially be lowered by several orders of magnitude within a few years. "Every step along the way will open up new possibilities."

The researchers can also measure the mass density of particles or cells "by varying the density of the surrounding solution," said Michel Godin, co-lead author.

The research team is already looking into several applications for the new technique. One area of great promise is creating a device that would mimic the cell-counting capabilities of flow cytometers. However, flow cytometry devices, which work by bouncing light off a flowing stream of cells, are too large and expensive to be useful in developing countries.

A tiny chip that could count cells using the new MIT weighing method would be a "cheap and robust" alternative to commercially available flow cytometers, which typically cost more than $20,000, Manalis said. "Since the device is batch-fabricated by conventional semiconductor processing techniques, it could potentially be used in a disposable format."

"Simply put, a cheap, simple CD4 counting device that can be used by a community health worker … would be a breakthrough advance in global health," according to Rodriguez.

Manalis is also planning a collaboration with MIT associate professor of biology Angelika Amon, who is interested in studying how the mass density of a single cell changes as it goes through cell division. Using the new method, scientists can ultimately trap a single cell and observe it over a long period of time. Changes in mass could correlate to production of proteins, offering a new way to study what the cell does during division, Manalis said.

Another application of the new technology is to measure small particles, or beads. It's important to know the size of particles used in paint, drug-delivery devices, coatings and nanocomposite materials, said Manalis, who added that the new technology could become the "gold standard" way to measure these particles one by one.

This illustration shows an artistic depiction of the concept that enables measuring the mass of a single bacterium and single nanoparticles in fluid with a very high resolution. A hollow resonator, represented by a hollow, fluid-filled guitar, vibrates while small particles, represented here by a bacterium, flow through it. As the particles flow through the resonator, they change the frequency (tone) of the vibration. (Credit: Image courtesy Thomas Burg)

Other authors on the Nature paper are Scott Knudsen, MIT postdoctoral associate in biological engineering; Wenjiang Shen, Greg Carlson and John S. Foster of Innovative Micro Technology in Santa Barbara, Calif.; and Ken Babcock of Innovative Micro Technology and Affinity Biosensors in Santa Barbara.

The research was funded by the National Institutes of Health Cell Decision Process Center, the Institute for Collaborative Biotechnologies from the U.S. Army Research Office, the Air Force Office of Sponsored Research, the National Science Foundation and the Natural Sciences and Engineering Research Council of Canada.
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The Max Planck Society Press Releases
Everything starts with Recognition 23rd April 2007
Asymmetry due to Perfect Balance 25th April 2007
Electrons Caught in the Act of Tunnelling 12th April 2007
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Mind, Body & Quantumness

Increasingly we are made aware that humans are composed of more parts than we can see or measure.

We have Stephen Hawking whose body suffers from a degenerative disorder yet is able to maintain a lucid (and brilliant) Mind. Of course we are aware that it is other parts of his body and not the brain, which are degenerating rapidly. The same with other degenerative conditions such as MS, where the 'person' is losing 'control' of the body, but retains an otherwise alert mind - unless of course they are struck by epilepsy or some other electrical imapct or damage to the neural system in the brain.

On the other hand we are becoming increasingly aware that in a 'modern' society like the US with over 5 million Alzheimer's sufferers, people with otherwise healthy or quasi-healthy bodies, and no discernible physical deterioration of the brain, are losing access to memory and memories.

Maybe there is information loss in black-holes. Of course it all depends what kind of information we are referring to, and which type of blackhole.

Though we may be able to look at the distant past and reconstruct a cosmological or geological picture of what might have been - we have absolutely no knowledge of peoples' thoughts (dreams, emotions, beliefs and memories) other than those carefully preserved in ancient scrolls, papirii or texts, and nowdays on 'record' (vynil) or tape (magnetic tape) or video tape, or more modern CDs, DVDs and the latest memory sticks.

Of course these are only but a fraction of any thoughts, or memories, or theories, which people have chosen to record or debate publicly whether thru course work or the internet.

We may even have some recorded mobile phone messages from 9/11 or those passengers on a flight before a crash, but in general most mobile phone conversations, like face to face conversations are discarded (or evaporate) into thin air as soon as they leave the speakers mouth.

But there is something more - we are increasingly becoming aware that man (or woman) is more than just their DNA. How the brain formed from that DNA, and is then educated or interacts with its environment - is what is commonly termed nurture (versus nature).

It has always been possible for a brilliant mind to be born into a severely disabled body, and equally it has always been accepted that a healthy body does not necessarily come accompanied by a smart brain, nor a healthy & lucid mind.

Furthermore it is increasingly becoming clear that is is not DNA or memory defines who we are. We cannot be selective with our DNA (yet) - we are born into it. But we are clearly selective with our memory, we can choose to keep (or romanticise) one memory whilst discarding another, and sometimes we cannot shake off a memory (pleasant or unpleasant) no matter how much we try. Though by enlarge few of us try to discard pleasant memories, since it seems we are seeking to create (or store) a selection & collection of pleasant memories and experiences. Bar in the few exceptions - which are not uncommon - where people strive for unpleasant, or painful and maccabre memories and experiences.

People often choose to remember or believe what they will.

Experimentalists probe the structure of the proton by scattering electrons (white line) off quarks which interact by exchanging a quantum of light (wavy line) known as a photon.
Visual QCD


So where am I leading with all this. It is to address the duality whereby some would like to believe that the DNA could carry not only our genes (always mutated) but some of our memory and the so called inherent abilities or skills (always truncated) - whilst others can more clearly see that one is independent of another. A king can be born the son of a carpenter, a musician can be born the son of a nuclear physicist, a painter can be born the son of a cleaner, and a Caesar can be born the son of a slave. All human hierarchies are purely artificial, imposed by the surrounding environment or society - and have nothing to do with Natural Law.

One still cannot give any verifiable testimony to the quantum leap 'life' makes from one lifeform (or lifetime) to the next. But this is only a mathematical equation. After all even the body you are in has already changed dramatically several times from the one you were in yesterday or yesteryear or ten and four score years ago.

The only thing that is clear upon death, is that there is something visible missing from the lifeless bofy or form. The lifeforce which gave it life.

And whilst all other information like memory, thoughts, feelings. emotions, may or not disappear down a blackhole (and reach a point of no return) it is clear that the lifeforce stripped of these continues thru Space and spacetime - to take up another form.

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Memory Restored In Mice Through Enriched Environment
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Mice whose brains had lost a large number of neurons due to neurodegeneration regained long-term memories and the ability to learn after their surroundings were enriched with toys and other sensory stimuli, according to new studies by Howard Hughes Medical Institute researchers. The scientists were able to achieve the same results when they treated the mice with a specific type of drug that encourages neuronal growth.

The results of the experiments suggest that the term "memory loss" may be an inaccurate description of the kinds of mental deficits associated with neurodegenerative diseases. "The memories are still there, but they are rendered inaccessible by neural degeneration," said the senior author Li-Huei Tsai, a Howard Hughes Medical Institute researcher at the Massachusetts Institute of Technology.

"I believe that these findings could have particular significance for treatment of people who already have advanced neurodegenerative disease," said Tsai. "Most current treatments seem to be aimed at affecting the early stages of the disease. But our mouse model shows that even when there has been a significant loss of neurons, it is still possible to improve learning and memory."

Memory Restored In Mice Through Enriched Environment
So doctor Tsai, can the mouse recognise its grandaughter?
Can the mouse memorise or remember how to play chess?
Can the mouse remember which bank it has an account with?
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Reversing Cancer Cells To Normal Cells
Multiple Sclerosis Is Increasingly Becoming A Woman's Disease
Brain Processes Sense Of Smell Better Than Previously Thought
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