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In Vivo Blood Pressure SensorA. Pillai and D. P. Nair

Introduction to Biosensors Final Report

ECE Dept., UMass Lowell,

AbstractBlood pressure measurement is an important diagnostic tool for ailments like dizziness, cardiac

arrest, strokes etc. Conventional methods, also called non-invasive methods are not accurate

when it comes to real time measurement of blood pressure. Hence, there is an urgent need for in-

vivo blood pressure sensors. The advantage of having an in-vivo sensor is that it is an attractive

proposition for continuous blood pressure monitoring and hence avoiding long term biological

effects. In this study, we began by reviewing existing in-vivo blood pressure sensors and then

found out what were the drawbacks for these pressure sensors. We are also proposing two

solutions to overcome the two problems that were affecting the performance of these sensors.

Keywords: Blood pressure, in-vivo, noise improvement, power dissipation

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IntroductionBlood pushing against the walls of the arteries causes a force, when the blood is pumped by the

heart. This is called Blood Pressure. Damage to the body can be caused in many ways if this

pressure rises and stays overtime. Coronary heart disease, Heart failure, Kidney Failure and

stroke are few of the symptoms of High blood Pressure (HBP) along with many other serious

health conditions.

It has been found that 1 in 3 adults in United States has a medical condition caused by High

Blood Pressure .Because HBP by itself shows no symptoms there is a good chance that a person

can have the disease for a long time without knowing about it. And during this time of

unawareness, the HBP can cause damage to the blood vessels, the Heart, kidneys and other vital

organs of the body. Checking and maintaining blood pressure numbers is important, even when

the person is feeling fine regardless of age and state of health. High blood pressure on the other

hand needs treatment and may prevent further damage of the vital organs. Low blood pressure

needs as much attention as high blood pressure, as it poses as many health risks as HBP.

One of the tricky things about BP is that it is never the same value. Activities like sleeping and

relaxing bring down the Blood pressure levels. Similarly blood pressure is expected to rise when

the person gets up or even gets excited, stressed out. or nervous. It is also high with levels of

activeness. If the numbers of BP remain above normal level even during moderate levels of

activity that is when there is a risk for health problems. Risk factors increase as the number

increases above 120/80 mm Hg or drop below 120/800 mm Hg.

A condition called "Prehypertension" basically states that there is a good chance a person will

end up having HBP unless steps are taken to prevent it . If a person is currently under treatment

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for HBP and show consistent readings in the normal range, the blood pressure is considered to be

under control. However, you still have the condition. You should see your doctor and follow

your treatment plan to keep your blood pressure under control. Your systolic and diastolic

numbers may not be in the same blood pressure category. In this case, the more severe category

is the one you're in. For example, Stage 2 HBP is when a person has a systolic number of 160

and a diastolic number of 80. If a person has systolic number is 120 and a diastolic number is

95, the condtion is called Stage 1 HBP. If the person has additional risk of having diabetes or

chronic kidney disease, HBP is defined as 130/80 mmHg or higher. Children and teenagers

exhibit different HBP numbers. Age is one main factor that influences HBP. Following a

healthy lifestyle is usually the best solution to delay or prevent HBP

In some cases, besides age and lifestyle, other diseases maybe responsible for raising blood

pressure. Problems such as chronic kidney disease, sleep apnea, thyroid disease, may cause

blood pressure to rise.. Medicines used to control certain diseases may also may raise a person’s

blood pressure. Asthma medicines and cold-relief products are few of the examples.

Damages caused to the body when the blood pressure numbers stay high over a long time include

the following:

An abnormal larger or weaker heart, leading eventually to heart failure. This is a

condition where in the heart cannot pump enough blood to meet the body's needs.

An abnormal bulge in the wall of an artery is a medical condition called aneurysm .The

main artery carries blood from the heart to the body; and these are the main spots for

aneurisms to occur. The brain, legs, and intestines all have arteries and this might cause

them to shut down. .

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Kidney failure may arise due to narrowing of the kidney vessels.

Affecting the arteries by narrowing them which are responsible, this limits blood flow

(especially to the heart, brain, kidneys, and legs). Causing medical conditions like heart

attack, stroke, kidney failure, or amputation of part of the leg.

Blood vessels in the eyes to burst or bleed. This may lead to vision changes or blindness.

When blood pressure is low, that is when another medical condition called Hypotension strikes.

It happens mostly because the body cannot bring the pressure back to its normal level at all, or

even fast enough. Low blood pressure sometimes occurs in some people all the time. This

usually means there are no signs or symptoms that cause them any discomfort, and a low blood

pressure s normal to them. In other people, certain conditions or factors cause abnormally low

blood pressure. Less blood and oxygen flow to the body organs is the result of this. For the most

part, hypotension is a medical concern only if it causes signs or symptoms or is linked to a

serious condition, such as heart disease. Signs and symptoms of hypotension may include

dizziness, fainting, cold and sweaty skin, fatigue (tiredness), blurred vision, or nausea (feeling

sick to your stomach).

The signs and symptoms of orthostatic hypotension and neurallu mediated hypotension (NMH)

are similar. They include:

Dizziness or light-headedness

Blurry vision

Confusion

Weakness

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Fatigue

Nausea

When low blood volume (from major blood loss, for example) or poor pumping action in the

heart (from conditions like heart failure, for example) causes shock:

The skin becomes cold and sweaty. It often looks blue or pale. If pressed, the color

returns to normal more slowly than usual. A bluish network of lines appears under the

skin.

The pulse becomes weak and rapid.

The person begins to breathe very quickly.

These two medical conditions are reason enough why measuring blood pressure is important.

Conventional Methods of Blood Pressure Measurement

NoninvasiveUnlike invasive techniques non invasive techniques are less expensive and virtually have no

complication at all. They are simpler and quicker, require less expertise and are least unpleasant

and less painful for patients. Their biggest disadvantage however lies in the fact that these

methods usually provide less accurate results with small differences in numerical values and also

cannot be used for long term continuous monitoring.. Routine examinations and monitoring

usually uses Non Invasive method of BP measurement.

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PalpationA minimum systolic value can be roughly estimated by palpation, most often used in emergency

situations. Historically, students have been taught that palpation of a radial pulse indicates a

minimum BP of 80 mmHg, a femoral pulse indicates at least 70 mmHg, and a carotid pulse

indicates a minimum of 60 mmHg. However, at least one study indicated that this method often

overestimates patients' systolic BP.

AuscultatoryThe auscultatory method (from the Latin word for "listening") uses a stethoscope and

a sphygmomanometer. This comprises an inflatable (Riva-Rocii) cuff placed around the

upper arm at roughly the same vertical height as the heart, attached to a mercury

or aneroid manometer. The mercury manometer, considered the gold standard, measures the

height of a column of mercury, giving an absolute result without need for calibration and,

consequently, not subject to the errors and drift of calibration which affect other methods. The

use of mercury manometers is often required in clinical trials and for the clinical measurement

of hypertension in high-risk patients, such as pregnant women.

Fig. 1: Auscultatory Method

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Oscillometric

The oscillometric method was first demonstrated in 1876 and involves the observation of

oscillations in the sphygmomanometer cuff pressure. which are caused by the oscillations

of blood flow , i.e., the pulse.  The electronic version of this method is sometimes used in long-

term measurements and general practice. It uses a sphygmomanometer cuff, like the auscultatory

method, but with an electronic pressure sensor (transducer) to observe cuff pressure oscillations,

electronics to automatically interpret them, and automatic inflation and deflation of the cuff. The

pressure sensor should be calibrated periodically to maintain accuracy.

Oscillometric measurement requires less skill than the auscultatory technique and may be

suitable for use by untrained staff and for automated patient home monitoring.

Fig. 2: Mercury Manometer

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Invasive

The most common techniques for monitoring blood pressure in small laboratory animals rely on

using an invasive catheter-tip transducer inserted into an artery. Tonometry is a minimally

invasive technique for a continuous measurement of pressure in blood vessels. The principle is

that if a vessel is pressed against a flat surface of a pressure sensor diaphragm until vessel

flattening occurs, according to Laplace’s law the pressure measured by the sensor will be equal

to the pressure inside the vessel.

In Vivo Blood Pressure Measurement

In vivo (Latin for "within the living") is experimentation using a whole, living organism as

opposed to a partial or dead organism, or an in vitro ("within the glass", i.e., in a test tube or petri

dish) controlled environment. Animal testing and clinical trials are two forms of in

vivo research. In vivo testing is often employed over in vitro because it is better suited for

observing the overall effects of an experiment on a living subject.

Two types of In Vivo Blood pressure Measurement1. Long-Term Implantable Blood Pressure Monitoring System2. Wireless Battery less In VIVO Blood Pressure

Sensing Micro system

Long-Term Implantable Blood Pressure Monitoring System

The system employs an instrumented elastic cuff, wound around a blood vessel, operating in a

linear “diameter v.s. pressure” region of the vessel for real time blood pressure monitoring. . The

elastic cuff is made of silicone or latex rubber, filled with low viscosity bio-compatible

insulating fluid with an immersed highly sensitive MEMS pressure sensor. The MEMS sensor

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enclosed in the cuff measures the pressure waveform, which represents a scaled version of the

blood pressure in the vessel, independent of the cuff bias pressure exerting on the vessel. This

method avoids vessel insertion, bleeding, and potential blood clotting. Furthermore, since the

cuff is made of soft elastic material such as latex or silicone rubber, and the stiffness of the cuff

can be much smaller than that of a blood vessel, the restrictive effect on the blood vessel is thus

substantially minimized while the soft cuff is in close contact with the vessel. This can reduce

the sliding-motion-induced signal drift, thus attractive for tolerating long-term implant variations

and minimizing adverse biological effects.

Wireless Battery less In VIVO Blood Pressure Sensing Micro system

A proposed wireless less-invasive implantable blood pressure sensing microsystem is depicted in

figure. The system employs an instrumented elastic circular cuff, wrapped around a blood vessel,

to sense real-time blood pressure waveforms. The elastic circular cuff is made of bio-compatible

elastomer and is filled with low viscosity bio-compatible insulating fluid, for example silicone

oil, with an immersed MEMS pressure sensor and integrated electronic system. The MEMS

sensor measures the pressure waveform in the cuff coupled from the expansion and contraction

of the vessel.

The measured waveform represents a down-scaled version of the vessel blood pressure

waveform and can be processed by a nearby integrated electronic system, consisting of a sensor

interface circuitry, an analog-to-digital converter (ADC), and a system configuration and control

unit for signal conditioning and coding, followed by a wireless data transmitter to an external

transceiver. The overall electronic system architecture is shown in the figure below. An adaptive

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RF-DC power converter is incorporated in the system design to provide a sufficient and stable

energy to the microsystem implanted in an un-tethered animal.

RF powering is used to eliminate the need of an implanted battery, thus substantially reducing

the overall implant size and weight. A miniature RF coil, can be employed to receive an

incoming RF energy to power the entire microsystem due to a low system power dissipation.

Fig. 3 Wireless in-vivo sensor

The adaptive RF powering capability was enabled to provide a reliable power supply for the

microsystem implanted in the freely moving laboratory mouse or rat. The measured digital blood

pressure information was transmitted to a nearby external receiver by the on-chip FSK oscillator

based transmitter.

The most common techniques for monitoring blood pressure in small laboratory animals rely on

using an invasive catheter-tip transducer inserted into an artery. Tail cuff devices require animal

restraint, thus resulting in a stress-induced signal distortion. Furthermore, tail cuffs can only

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obtain systolic and diastolic blood pressure levels instead of a continuous blood pressure

waveform with detailed signatures, which are desirable for advanced biomedical research. Both

technologies, therefore, are inadequate for real-time long-term monitoring. This is where

wireless, batteryless long term implantable blood pressure monitor is desirable.

Microsystem Architecture

Fig. 4 System architecture

The overall electronic system architecture is presented in Figure 4. An adaptive RF-DC power

converter is incorporated in the system design to provide a sufficient and stable energy to

the microsystem implanted in an un-tethered animal. RF powering is used to eliminate

the need of an implanted battery, thus substantially reducing the overall implant size and

weight. A miniature RF coil, can be employed to receive an incoming RF energy to

power the entire microsystem due to a low system power dissipation.

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Objectives

We found that there were two significant problems with the sensors that were specified in the

background:

a) Increased noise levels

b) Very high power dissipation

A) Increased noise levels:

The measurement data after animal implant recovery exhibits an increased noise level, which is

likely due to animal body vapor penetration through silicone coating to the capacitive MEMS

pressure sensor and the electrical connections between the sensor and IC chip. The top

electrode of the capacitive MEMS pressure sensor, which is implemented by a sensor

diaphragm, is connected to the C/V converter summing node. This high impedance node can

be highly sensitive to vapor penetration. Therefore, protection for moisture penetration is

required for the sensor diaphragm as well as the electrical connections between the sensor

diaphragm and IC chip.

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Fig. 5 Implementation of sensor inside a laboratory test subject

B) Very high power dissipation

An oscillator-based FSK transmitter was employed in the microsystem for data telemetry.

The transmitter was on throughout the entire operation in the prototype design, dissipating an

80% of the system power.

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Solutions proposed

A) For increased noise levels:

A passivation layer, such as silicon dioxide (SiO2 ) and silicon nitride (Si3N4 ), can be deposited

on the top of diaphragm; and encapsulant material with strong moisture resistance can be

used to protect the bond wires between the sensor and IC before applying silicone

passivation layer. Improved packaging methods are, therefore, crucial to enhance the reliability

of the micro system for long-term blood pressure monitoring.

B) For reduced power dissipation

To minimize the overall system power dissipation, a transmitter operating with a low

duty cycle scheme and an increased transmission bandwidth can be designed. For example,

the sampling frequency of the prototype system is 2 kHz with a data rate of 48 kbps,

corresponding to a 24 bits data frame per 0.5 ms. The transmitter can be designed to be on

for 0.05 ms for data transmission and off for the remaining 0.45 ms, resulting in one

order of magnitude power reduction at an increased data rate of 480 kbps. This corresponds to a

72% overall system power reduction.

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Timeline

Since we were only two project members each one of us took one of the objectives. In the first

four weeks of February we were researching in-vivo blood pressure sensors and were preparing

for report 1. We did find a lot of unique conventional blood pressure sensors but not many were

in vivo ones. However, in time for report one, we did find two in vivo blood pressure sensing

mechanisms. But the second design had two problems that were listed above and we chose our

objectives such that by first week of March we had the first objective ready. This was included in

the first report. And the second objective was researched upon and it was proposed in the final

report.

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Conclusions

The objectives of this research have been successfully achieved. A cuff-based less-invasive

blood pressure sensing technique was developed and demonstrated. This technique avoids vessel

penetration and substantially minimizes vessel restriction due to the soft cuff elasticity, thus

attractive for long-term implant. Wireless, batteryless, less-invasive, and implantable blood

pressure sensing microsystems with data telemetry and adaptive RF powering capabilities for

both laboratory rats and mice monitoring were designed and demonstrated.

The demonstrated wireless implantable technology will become an important research tool

for system biology research. It is expected that the proposed sensing technique with

microsystem engineering design will be desirable for future human-based health monitoring.

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