7.5.

2007

Body implanted MST

AS-74.3136 Introduction to Microsystems
Markus Hartikainen 77777M

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Body implanted MST...........................................................................................................................1

1. Introduction..................................................................................................................................3
2. The overall picture in using MST on future’s medical devices .......................................................4
3. Body implantable MST....................................................................................................................5
3.1 An implantable drug delivery system for treating diabetes .......................................................5
3.2 Implantable sensor systems........................................................................................................9
3.3 Neurotechnology for restoring neural functions ......................................................................10
4. Sources ...........................................................................................................................................12

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1. Introduction
Microsystem is referred to as a system in which as many functions as possible are realized within a
very small amount of space and which has at least one micromechanically manufactured component
[1, p.1]. The development in the field of Microsystems technologies have been evolving rapidly
since the past decades. Lots of that contribution has happened thanks to the micro chips. Scientists
have tried to make smaller and smaller microchips with more and more transistors packed inside the
circuit. The techniques of manufacturing different kind of microsystems from silicon have
simultaneously given ideas for many new packaging and production techniques.

NEXUS

Microsystems are a matter of definition within

the many technologies they connect

microelectronics

nano techniques MST

optics

Precision mechanical
“milli” techniques

August 1, 2002 Presentation of the NEXUS Market Analysis 2000-2005 3

MST can be applied to many areas such as medical technology, automation technology, robotics,
metrology, chemical analysis, car manufacturing, electronics etc. This article narrows down to just
one specific field of the applications that can be implanted in the human or animal bodies. There are
already few applications in the medical field that are considered to be microsystem technology.

Minimal invasive surgery/therapy solutions are becoming more common. Natural orifices and small
incisions have been used in endoscopy since the late 1980’s. First just for diagnostic, but later on to
minimal invasive surgeries, too [1, p.27]. In endoscopy, digital cameras and other manipulators and
actuators can be inserted so the surgeon can see what is happening inside the human body and with
a great accuracy. Endoscopy though, can in some cases be replaced with a swallowable tiny pill

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which has a camera inside it. It travels through the human digestive tract and takes pictures and
sends those outside the body via radio connection to the operator.

A pacemaker has been a breakthrough in medicine. It’s one of the smallest artificial organs yet. In
the USA, 120 000 of these systems are needed per year [1, p.30]. Hearing aids are quite commonly
known, too. These products can still be vastly improved by using MST. The biggest problems with
prostheses are microactuators and energy supply. MST in producing microactuators isn’t yet so
evolved technology than in many other fields of it. Human organs use chemical energy but when it
comes to implanting an artificial system in a human body, other energy sources are required.

2. The overall picture in using MST on future’s medical devices

The development of MST can be categorized into three sections: computerization, miniaturization
and molecularization according to the article in MST News (volume February 1/06) [2, p.6].
Progress in these areas have been successful. The enhanced computing power will result into
telemetric solutions to monitor various physical parameters in a human body from a remote location
(home care for elderly, patient area network, electronic patient data card) [2, p.6]. The
miniaturization gives possibilities for different delivery- and therapy systems. Molecularization
means intelligent biohybrid body implantable systems including manmade electronics combined to
biocomponents (cells etc.). According to Dr. Robert Farkas [2, p.7], diagnostics is currently more
focused in field than therapeutic solutions. The economic forecasts for the year 2007 predict ca. 30-
50 million € for drug delivery as one example of therapeutic innovation while the estimated
turnover for diagnostic biochips is about 450 million € in the year 2005. Despite of these figures,
the development of new MST technology often requires many years of research without any
guarantees for the profit before it can be commercialized.
The future’s innovations depend on the interdisciplinary research and the skills for
productize those ideas. The Microchips are produced smaller and smaller via the evolving silicon
processing techniques. At the same time the dimensions of systems are being miniaturized. Small

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applications require more efficient computing and storage power from the processors. New
manufacturing techniques are needed for shrinking the dimensions.
Many MST manufacturing techniques already exist: Layer techniques, thin/thick film
techniques, micromechanics, integrated- and fiber optics. There are also many methods for
producing micromechanical components: Silicon fabrication techniques, Doping, Lithography,
Etching techniques, Lift-off technique, Surface and bulk micromachining and LIGA technology just
to name few. Those methods can be studied in the pioneering MST book written by Sergej Fatikow
and Ulrich Rembold in 1997.

3. Body implantable MST

In this section I try to give different kind of examples of the existing and oncoming body
implantable applications. There’s already market area worth billions of euros in the world for these
kinds of therapy and monitoring solutions.
The uses of MST in future’s medical devices are often case-specific. Researchers can
get an idea about one field they want to concentrate in and that project work can give a new solution
or even a new product. Many times though, those ideas just can’t necessarily be applied in other
fields. This decentralizes the R&D of MST to various fields even just in one field: implantable
devices.

3.1 An implantable drug delivery system for treating diabetes

There are already insulin pumps in the market using ambulatory infusion
pumps. These gadgets require regular and expensive maintenance [3,
p.17]. Nowadays infusion pumps are particularly more common among
the children who suffer from diabetes.
A piezo-electric pump with a flow sensor ensures an
accurate delivery of the drug liquid. The drug compound liquid is held in a
reservoir integrated in the package among everything else. A patient
carries the device on her/his belt.

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There’s a shut-off valve between the patient and the device that will work if the
pump’s control signal is saturated or if it works outside a safe flow level. The device is controlled
with a microcontroller. The flow sensor senses the flow using a pressure sensor.

The insulin pump is used to deliver basal insulin continuously and bolus insulin manually at
meal times. A single blood glucose value is entered as a "snapshot" when bolusing to
bring the blood glucose level back to the target value.

The biggest problem using an insulin pump outside the body is that one has to change
the liquid inline spot at least after every four days to avoid the infections. Besides, nowadays the
device doesn’t measure the blood glucose level itself but the patient has to tune the pump’s flow to
an accurate level that suits her/himself. These reasons can make the pump impractical to use.
Despite of this constant manual tuning problem there were 500 persons in Finland using this kind of
device according to the Diabetes magazine’s article in 3/1999 [4]. In Germany 9000 users existed
and in the North America the numbers of the users were approximately 32000.

An implantable subcutaneous drug delivery system for the people who are suffering
from diabetes is one vast and challenging project for the researchers. The system could be called
artificial pancreas. So far, there are at least three considerable approaches to this challenge: The
medical equipment approach, the bioengineering approach and gene therapy [5]. The medical
equipment actually isn’t being placed under the skin but the continuous glucose sensor transmits the
data by using radio frequencies.

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1 - Continuous glucose sensor monitors blood sugar level

2 - Data transmitted for the computer programme to work out insulin dose
3 - Insulin pump delivers the dose

The benefits of the continuous blood glucose level monitoring are quite obvious. The
whole monitoring can be made automatic without the user’s action. Trends monitoring and saving
for the use in future are important in the prediction of the glucose level peaks and lows during the
day. The continuous monitoring means closed loop control and the ordinary insulin pump treatment
is considered to be an open loop system.
The continuous sensors require calibration few times a day. The user has to then enter
the right blood glucose values for a sensor correction. The continuous sensors measure the
interstitial glucose and therefore there is a time delay between the sensor data and the true blood
glucose.
The basal and bolus rates can be controlled with a feedback loop and using adaptive
filtering techniques, the unique required drug rates for the person can be learned as a function of the
time of day [5].

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If the whole device was being put under the skin, the challenges are the refilling of the
device without operating on the patient (required amounts of insulin drug liquid compound for a
person per month are close to 10-30 ml). This includes many additive ingredients and injection
liquids. Besides there are many kinds of artificially produced insulin available and it’s very case-
specific what suits whom.
Normally one needs two differently affecting insulin. The bolus compound works as
rapidly affecting (starts working 10-20 minutes after injection and has an effect to 3-5 hours after
injection) and basal works for longer periods (one takes it usually in the mornings and evenings;
two times a day).
So the insulin drug compounds may have to be stored subcutaneously in two separate
containers and both containers have differently working control loops. Those loops should contain
glucose sensors and controllable dosing MST pumps. If you think that this is still easy to handle,
this drug delivery system should work robustly 24 hours a day for years with very little
maintenance.
The user should be able to change the control modes on the fly. This is because a
person’s need for the insulin is strongly dependent on how much the person exercises. For example
if you think of going jogging you have to stop keeping the blood glucose level at the 4.0-6.0 mmol/l
hours before the exercise. You either have to change the reference value of the drug delivery system
manually or in the system itself is programmed the person’s usual work out hours. That could be
done using a wrist watch or a laptop that is connected to the device using radio signals or bluetooth.
The wrist watch’s User Interface could contain several different control modes: normal (4.0-6.0
mmol/l), sport (6.5-9.0), extreme (7.5-11.0).
One solution for overcoming this refilling problem described in the Fatikow’s and
Rembold’s book [1, p30] is a swallowable capsule which can be destroyed by external signals. That
could work in other illnesses but not in treating diabetes. This is so, because insulin has to be
injected in the muscle so that it disperses gradually to every part of the body. Another idea to tackle
this obstacle is to place the system underneath the skin so that the user can do the refilling with
more traditional way by using the insulin pen for example two times a month.
First clinical tests on implantable insulin pumps were started in the beginning of 2007
in France and in the United Kingdom. The implantable sensor is inserted into a neck vein leading to
heart. The sensor is connected by wire to the insulin pump. In 95% of cases the sensor measured
accurately compared with values obtained by finger sticks. The desired blood glucose levels were
maintained more than 50% of the time. The pumps’ lifetime is approximately eight years and the
sensors’ nine months.

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I think that this would make the diabetic’s life much easier and controlled. The biggest
problems with this disease according to diabetics aren’t the injections but the lack of continuous
measuring and a feedback loop in a form of a drug delivery control system that makes the automatic
monitoring and treating possible.
Still the system’s energy consumption has to be very low and even though batteries
can last for several years, it’s too big task to replace those by the means of a surgery. Rechargeable
batteries that use chemical energy or recharge themselves from the human body movement could
offer a way to avoid the battery replacement by a surgery.

3.2 Implantable sensor systems

Implantable sensor systems can be handy when you need permanent monitoring of various physical
parameters such as blood pressure, heart beat rate, temperature and so on. All these measuring
devices should be very reliable, inexpensive and biocompatible so that a human body does not
reject the device’s existence. Many steps have to be taken until these demands are met. The medical
field includes the responsibility issues: if something goes wrong who is then responsible for it. This
slows down the development of the medical MST devices. Though the progress is inevitable.

Multi-site pressure sensing catheter

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3.3 Neurotechnology for restoring neural functions

Scientists have tried to restore some neural functions in the human body by using microstructured
neuronal connections between regenerating peripheral nerves and external electronics. There a
silicon microstructure serves as a neuronal interface. There are holes in the silicon chip which are
surrounded by electrodes. Those electrodes allow recording and stimulation of individual axons.

Scientists have managed to make an electrode arrangement in which they implanted

the cut ends of rats’ peripheral taste fibers and nerve fibers functionally regenerated through the
micro holes. These neuronal interfaces could be used in motorized/sensory prostheses. It will be
possible to control a prosthesis by the functional electrical stimulation. For spinal cord injuries
involving severed nerves it should be possible to bridge over the interrupted nerve paths allowing
affected body parts to be directly stimulated [1, p.33]. This interface works as bidirectional
connectors between the peripheral human nervous system and external devices.
After the neurochip is implanted, neural cells grow through the holes making a
mechanical and electrical connection between the neurons and the control electronics. The chip is
integrated into a guiding channel that allows the growing of axons and the fixture of the chip. After
the connection between the electrodes and nerves is established, the control signal for the prosthetic
device has to be generated. This is done by transforming and decoding the neural signals into
electronic data and vice versa with an external electronic device to process data flows in both

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directions. The last and probably the most challenging task then is to develop an intelligent control
system that can reliably interpret biological signals and act on them [1, p.34].

In these days in the hospital of Töölö, surgeons use neurosurgery on a daily basis. For
example it’s already possible to do the local anesthesia by searching the right nerve axon with a
weak electric current applied on a patient that controls the wanted part of the body (a finger for
example) and inject the anesthetic there (in this finger example, the axons are in the armpit area).
The markets are wide and profitable for neurotechnology after a fully functional device has been
developed.

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4. Sources
[1] Sergej Fatikow and Ulrich Rembold, Microsystem Technology and Microrobotics, 1997
Springer, Berlin Germany

[2] MST News, Integrated Microsystems for biomedicine, February 1/06, VDI/VDE Berlin,
Germany

[3] MST News, Biomedical and Pharmaceutical applications, Number 4/00 September 2000,
VDI/VDE Berlin, Germany

[4] Diabetes-lehti, Insuliinipumppu tyypin 1 diabeetikon hoidossa,

http://www.diabetes.fi/sivu.php?artikkeli_id=495

[5] Wikipedia, Artificial Pancreas. 5.4.2007. [Referenced 22.4.2007]. Accessible at:

http://en.wikipedia.org/wiki/Artificial_pancreas

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