A paper thin sensor to check on your cardio-vascular system

It really looks like a plain bandage but if you detach it you’ll discover a patch, not bigger that a stamp that is able to sense variations of tension on your skin with a very high precision.

You can see it in the photo on the side (credit: L.A. Cicero/Stanford University): it has been designed to monitor not just your heart but also the cardio-vascular system as a whole.

When our heart beats it sends a pressure wave that is detected by the sensor under the bandage. Its strength and periodicity can provide important information on your heart workings. That first pressure wave is followed by a much tinier set of waves generated by the tissue response to the first wave (like a spring that is compressed by the first wave and then bounces back once the pressure wave is gone). These further waves can tell a lot about our vascular system: a sclerotic vein, or artery, generates a different response to the pressure wave than a normal vessel. By being able to capture and measure the tiny variations of these waves the sensor can provide most useful information on the status of our cardio vascular system. Obviously, the sensor is just picking up the variations of skin tension but these variations are transmitted to a computer, the one in your smart phone would be perfect, for analyses and comparison with previous sets of measurements so that even more meaning can be derived.

Notice that the cell phone might act as an integrator (this is my speculation, not presented by the researchers at Stanford), picking up information about your movement, as an example: if you are jogging (and this can be inferred by the cell phone accelerator, or if you are walking in a city rather than in a forest, by the seaside or on a mountain (and this is known through the positioning system in your cell phone) the data coming from the sensor lead to a different sort of information and all together, taken in different situations, can provide an amazingly accurate picture of the health of your cardio vascular system.

To create such a precise, flexible and unobtrusive sensor researchers at Stanford have overlaid on a thin rubber sheet two electrodes. The whole is thinner than a dollar bill. The rubber band is composed of tiny pyramids. Variation in the tension of the skin produces a variation in these pyramids, just a few microns each, and in turns changes the distance between the two electrodes leading to a variation in the electromagnetic field. Et voila! these is the data provided by the sensor to the computer for analyses.

The system is both sophisticated (a very precise distribution of the pyramids) and simple and so it is easy to manufacture at a very low cost. We can expect to find these kinds of monitoring devices on our body in the near future with our cell phone acting as the local interpreter of what is going on and as a relay point to more sophisticated analyses.

Today the evolution of diagnostic methods and intervention is in the direction of less and less invasive procedures. Biopsies are often made using needles and catheters thus minimising tissue trauma.

Look at the micro gripper, the yellow-orange speckle on the side of the tip of a catheter

Well, apparently there is still room for less traumatic procedures.

Researchers at the John Hopkins have developed an ingenious system using smart materials to create tiny pinchers, the size of dust, that can be swallowed or introduced in vessels.

The idea is to introduce hundreds of them and have them swarming through your (our) cavities. You can see one of them in the photo on the side and if you look well you can see a sort of 6 legs that are, as a matter of fact, pinchers that closes on the surface of a tissue and grab a few cells removing them from the surface.

This is done in a random way and having hundreds of them creates a good statistical sampling of the tissue needed to be biopsied.

Each micro-gripper is built using a smart material that changes its shape when heated. And indeed they are introduced as frozen bits that warm up once the get inside the body.

To remove them and retrieve the biopsies (the cells) the doctor uses a magnetic field. Since they embed a magnetic particle they are sensitive to magnetic field, and like iron filings they follow the magnet.

Hundreds of micro grippers in a vial

The researchers have demonstrated the viability of the system by putting it at work in the esophagus and colon of a pig (gastrointestinal tissue of pigs is quite similar to the one of humans).

The goal is both to decrease the invasiveness of biopsies and to increase their reliability. In many procedures, like in the case of esophagus and colon, the number of samples that are taken today (30-40) is not high enough to provide a good statistical value, in other terms the doctors may miss a cancerous area with dire consequences.

Multiplying the samples reduces the risk without prolonging the procedure and using smaller number of cells for each sample.

Of course, I can imagine that this is going to multiply the data that are being accrued on each procedures and over time we can see our digital self growing in size.

3D printing is already being used in health care for skin and more recently bones. Scientists have promised that by the end of this decade technology will allow the printing of whole organs. And, looking at the news appearing on scientific journals it looks like they are going to make it.

Cross-section of multi-cellular bioprinted human liver tissue, stained with hematoxylin & eosin (H&E) (credit: Organovo)

In a NewScientist article we can read that Organovo, a California company, has announced the availability of  liver tissue printed using a 3D printer (and related software). It is the first time that a perfectly working liver tissue has been created.

The photo on the left hand side shows the liver cells and the space between the cells that is formed by cells that are on the internal lining of blood vessels.

So far Organovo has managed to create a thin layer of liver cells half a mm thick and 4 mm in length. It has been obtained by growing hepatocytes and stellar cells in culture and then using them as the “ink” for the 3D printer that has created the liver structure (also inserting the lining to allow perfusion). The 3D printer prints one layer over the other, a total of 20 of them, creating the correct 3D structure.

Up to now aggregates of liver cells where all what was available to researchers studying the effects on drugs “in vitro”. Those aggregates, however, are not really working as a liver and survive for just two days.

On the contrary, the liver tissue created by Organovo behaves like a normal liver, processing metabolites and producing albumin, cholesterol and a few enzymes and can function normally for 5 days. This is ideal for researchers experimenting the effects of drugs.

The company is selling this tissue to pharmaceutical company but the long term objective is to produce a normal liver for transplant. The idea is to use a few cells, still working properly, from the person needing a new liver and culture them till there is a sufficient number to “print” the brand new liver.

If this is likely to require at least 10 years, they expect to be able to produce a part of a liver that can be implanted to supplement the fading functionality of a compromised liver.

Have you ever heard people saying: “a bulb light moment!”. You got cartoon showing the bulb shining light over your head and in Italy we go as far as saying that “a light has lighten up in my brain”.

Tiny LED on the tip af an optical fibre

Well, it appears that scientists have taken this slang for real and have been working to really light up the brain and to see what happens!

They discovered that neurones can be made sensitive to light, by manipulating the genes, in what is called optogenetics. By inserting an optical fibre in the brain of a rat whose neurones were conditioned to be sensitive to light, it was possible to influence, through light pulses, the reactions of neurones. They proved that light pulses stimulate neurones to produce dopamine and in turns this chemical changes the overall processing of neurones. In the experiment scientists stimulated the pleasure areas of the brain rat.

The optical fibre terminating with a LED was specially developed by a team at the university of Illinois, it is thinner than a human hair.

Having assessed that the next step was to invent a device that could be implanted in the brain and that could generate pulses of light. This is what they managed to do.

A LED amongst kidney cells

As you can see in the photo they managed to create a tiny LED that can be radio controlled and whose dimensions are similar to the dimension of a neurone (in the figure the LED is compared to kidney cells, and their size is similar to that of neurones).

So far the technology developed has been used to understand brain connections but in the future the researchers expect it to be applied to a variety of situations, extending also to other organs.

A first application is foreseen in the management of chronic pain, inserting LEDs that can interact with peripheral nerves to block pain signals.

They also expect that by using different colours it can be possible to activate different “circuits” in the brain, hence increasing the level of control possible.

Whilst application in health care is important, the growing understanding of the brain and the possibility to control it raises ethical issues that we never have to face before.

The dream of sending tiny vehicles inside a human body to deliver medicine or perform micro-surgery is not new at all. But it is just now that we can see this dream turning into reality, at least moving the first steps into reality.

A team of researchers at the University of California have presented the results of their work on self propelled rockets and motors at the micro and nano scale, so small that they can travel within a human body.

The idea is to have engines that can use as fuel body fluids. As an example, a micro-rocket designed to operate in the stomach can use the HCl (hydrochloride  acid). Indeed that is what the team did. They managed to create molecules that act as enzymes decomposing the HCl into H and Cl: this creates a jet stream of tiny bubbles of H that propels the rocket. See drawing on the left – Credit: Credit: Wei Gao and Joseph Wang, Ph.D.

Similarly, but using different fluids/molecules, the designed micro-rockets that can operate in blood vessels and intracellular fluid, including the cerebra-spinal fluid. These use as fuel glucose (sugar) molecules and by decomposing them they create droplets of water that are exhausted and propels the rocket forward.

The important thing is that both the fuel and the exhaust material produced are normal presence in the body, therefore they are not interfering with the body metabolism.

It is clear that these are just tiny steps towards the fulfilment of the dream, but they are necessary ones. Having a truck is not enough to deliver your payload. You need to load the truck, provide directions on where to go and how to get there. make sure that the payload is delivered at the right location undamaged and so on. All these different components of the puzzle are under study and we are no longer dreaming but designing a complex system knowing what we have and what we are missing.

Researchers foresee a different area of application (that may actually happen sooner): cleaning oil spills by using oil as a fuel at the microscopic level, decomposing it into harmless molecules.

Electronics is slowly but steadily make ways in our bodies. Microchips to release drugs, sensors to detect a variety of conditions are already part of the landscape.

The crucial problem to solve remains the powering of these devices. As electronics evolution (Koomey’s law) keeps decreasing the demand for power new approaches are becoming feasible, such as the one proposed by Jia Hao Cheong, a professor at the A*START Institute of Microelectronics in Singapore.

He is addressing the problem of monitoring grafts in the body that surgeons are implanting to create an artificial blood vessel (or substitute a faulty one). The problem with these grafts is that they may become clogged and it is important to monitor what is going on. The solution proposed is to insert in the graft material nanowires that change their resistance as they are stretched, somthing that happens when the blood pressure increases. A sensor can measure this pressure increase by detecting the change in resistance of the nanowires but of course the sensor needs to be powered.

Cheong has found the solution by sending the power wirelessly from the reading device that the doctor holds in her hand, like it is done when reading RFID tags.

As shown in the figure the graft (in this case used in people with kidney failure that need to have dialyses every few days and have a graft implanted to avoid pricking the veins with possible damage and infection) is being monitored by a tablet like device that is sending wireless power sufficient to activate the sensor for both reading the strain in the graft and sending the information, wirelessly, to the tablet.

The power transmitted by the tablet is absorbed also by the body tissue but it is sufficient to power a 12.5 microW sensor up to a depth of 50mm, which is plenty for a graft inserted in arm.

The tiny implant

EPFL has announced the development of a “sensors” that can be embedded under the skin to test blood. It communicates via radio to a patch on the skin that provides also the energy. This latter transmit via Bluetooth the information to the cell phone where an apps provides to transmit it to the doctors computer.

The impact, a few cubic millimetre, contains a sensing array able to detect a variety of molecules, not just the ones in the blood, also the ones that percolate in the intracellular fluid. And of course, you can expect that this is just the start. More and more substances will be detected in the future!

The implant is set a few millimetre under the skin, and can be placed there using a special injector in a matter of seconds. A patch is then positioned over the skin. This patch contains a microchip to manage the communications with the sensor and the one with the cellphone. It also contains the battery to power the chip and the sensor (via radio waves).

The patch shall be charged every few days (or more often depending on the frequency of measurements).

I really see a changing medicine unfolding where telecommunications is a key enabler.

The microchip array with 1,500 pixels plus some used for testing purposes.

Just a week ago I posted the news of the first FDA approval for an eye implant to mimic (partly) the retina. Now I stumbled upon another news reporting the achievement of German and Hungarian researchers that have created and implanted a retina prosthetics with a resolution of 1,500 pixels, and this is quite a lot if you are comparing to the first prosthetics that had just 16 pixels.
With this kind of resolution the 9 blind persons that have received the implant have been able to read a few letters as shown in the clips you can see here. One of them pointed out that his name was misspelled!

The implant, shown in the photo on the left, is placed under the retina in the fovea region. Each of the 1,500 photosensors captures the light and generate a tiny spike, mimicking the behaviour of a retinal sensor (a cone or a rod). This spike is relayed to the brain via the optical nerve. The implant is 3*3 mm and is connected to a coil placed in the ear region that serves as an antenna to receive power from an external battery.

Notice that in this case the implant replaces part of the non functioning retina but still uses part of the retina to communicate with the optical nerve.

It is the implant that receives the light coming through the eye and the spikes generated are processed by the remaining two layers of the retina, still functioning.

The brain, therefore, continues to receive the information from the eye itself and from the muscle of the eye (saccadic movement) as in the norma functioning sight. Of course this is better but also makes this kind of prosthetic possible only in those situation where part of the retina still works.

Bio-printing is already a reality, being used to print skin for patients having suffered from burns. We have had last year the first 3D printing of a mandible to substitute one affected by cancer.

3D printer in the process of printing a ear

Now researchers at Cornell University have announced the development of a process to print ears, using 3D printers.

Even though we may not consider our ears as a sophisticated device, just a piece of skin -right?!, they are. Their shape is the result of hundreds of thousands of years of evolution to come up with the right form, ensuring a good capturing of sounds.

There are thousands of children born without a fully developed ear, a congenital deformity called microtia, that can benefit from this research, in addition to people who had lost their ears because of an accident or cancer.

The researchers are using a gel with embedded living cells (from cartilage tissue) taken from rats and cows (click on the link to see a detailed description of the process used). Once implanted, the gel will be replaced by that person cells. The cartilage tissue (cells) don’t need to be vascularised, hence there are no problem with a patient rejecting the ear. However the researchers are working to be able to use as initial cells some taken form the patient to avoid any problem.

The 3D printer creates an ear that is basically indistinguishable from a natural one, using a 3D model created by laser scanning. The whole process can be done in a few weeks. So far there have been no implants but researchers are expecting this to happen within the next three years.

In the last decade scientists forecasted that within ten years they would be able to create a bionic eye, that is to implant in an eye that has lost the capability to “see” a chip that can recreate that function. There are many people who have lost their sight, many after having been hit by retinitis pigmentosa, a degeneration of the retina leading to blindness.

Schematics of a retinal implant

Scientists have followed two approaches to restore sight: implanting electrodes on the visual cortex to simulate signals received by the eyes and implanting a chip on the faulty retina to connect directly to the optic nerve. The latter is by far the better approach, but it is also the most difficult one.

It is therefore a great news to see that the FDA has granted the first approval to a chip for implant in the eye, the Argus II.

The chip is part of a system to provide visual stimuli to the optic nerve: a pair of glasses embed a video camera that sends the images being captured to a tiny computer worn by the person. In the future we can expect to have this computer embedded in the glasses (the critical issue here is the size of the battery).

The computer transforms the images into signals that are brought back to the glasses to be transmitted via an antenna to the chip implanted on the retina. The transmission is also providing the power for the chip to capture the signal and relay it to the optic nerve.

The signals are not exactly the same as the ones that a normal functioning retina would provide to the optic nerve but they are close enough to let the plasticity of the brain to interpret them. After a while the brain rewires itself and accepts these signals as the “usual” visual signals recreating the image on the visual cortex.

The images that are perceived are quite a long shot from the images that a normal retina is able to create. Here the person is able to see light in different shades and so become aware if it is dark or not and can recognise forms well enough to find her way in a room without bumping on a chair or a table. There is no way, today, to recognise a face, nor to read a book.

But this is TODAY! The biggest issues have been resolved and now it is a matter of evolving to increase the resolution and the variety of signals. And we know very well that evolution is an intrinsic property of electronics. I am therefore quite confident that by the end of this decade we will be able to implant a chip that would allow a blind person to read a book and to recognise her friends. And this looks more like magic than technology!