Concept Design of a New Portable Medical Device for Lymphedema

Monitoring: A EIT Health ClinMed Summer School Project

Jordi Escuder Tisaire

, Elena Martín Rodrigo

, Sofia Ribeiro

2,3,

, Mariachiara Ricci

Juan Sebastian Cuellar

, Dimitrios Zeugolis

3,6

, Yves Bayon

and Isabel Rocha

Universitat de Barcelona (UB), Gran Via de les Corts Catalanes, 585, Barcelona, Spain

Medtronic, Sofradim Production, Avenue du Formans 116, Trevoux, France

Regenerative, Modular and Developmental Engineering Laboratory (REMODEL),

National University of Ireland Galway (NUI Galway), University Road, Galway, Ireland

Department of Electronic Engineering, University of Rome “Tor Vergata” (Rome), Via del Politecnico 1, Rome, Italy

Department of Biomechanical Engineering, Delft University of Technology, Mekelweg 2, Delft, The Netherlands

Science Foundation Ireland (SFI), Centre for Research in Medical Devices (CÚRAM),

National University of Ireland Galway (NUI Galway), University Road, Galway, Ireland

Faculty of Medicine and Cardiovascular Centre of University of Lisbon, Avenida Professor Egas Moniz MB,

Lisbon, Portugal

Keywords: Breast Cancer, Bioimpendance, Lymphedema, Screening, Self-Monitoring.

Abstract: Lymphedema is a chronic and progressive condition derived from impaired lymphatic system function.

Lymphedema is incurable, progressive, disfiguring, disabling and has adverse psychosocial effects. Upper

extremity lymphedema is mainly the consequence of breast cancer surgery. Several methods to diagnose

lymphedema exist; however, these diagnoses are performed once the disease is already close to an advanced,

irreversible stage. There is a need to monitor patients at risk with an efficient device. To solve this unmet

need, we propose a portable home-monitoring device for early diagnosis of lymphedema. This paper explores

all the aspects of the development of a new medical device, such as the assessment of the clinical need and

the state of the art, the specifications for the solution, the definition of the broad outlines of the development

plan and some considerations about the usability, the risk analysis, the market and the competitors.

1 CONTEXT

This work was born as a team project developed

during ClinMed 2018 summer school. ClinMed is a

summer school of EIT Health co-organized by

Inserm, Karolinska Institutet, University of

Grenoble-Alpes, University of Lisbon, Medtronics,

Becton Dickinson and Madopa. This summer school

aims to train participants on the technological

innovation in health by providing a global vision of

the maturation cycle of a medical device, i.e. from the

idea to the market, using the concept of experiential

learning. After an immersive stage at Rehabilitation

service at the Hospital Santa Maria (Lisbon, Portugal)

and the Pediatric Cardiology department at the

Hospital Santa Marta (Lisbon, Portugal), and in

collaboration with the clinicians, a real clinical need

*These authors contributed equally to this work.

was identified, and its solution explored during the

summer school.

2 INTRODUCTION

Lymphedema is a chronic and progressive disorder

which causes an accumulation of lymph fluid

(swelling) in parts of the body where lymph nodes or

lymphatic vessels are damaged or inadequate. It is

caused by an accumulation of fluid in the interstitial

tissues, due to the inability of the lymphatic system to

transport lymph fluid out of the affected area.

Lymphedema is classified as primary or secondary.

Primary lymphedema is rare, with an estimated

prevalence of 1 in 100,000 individuals and is caused

by lymphatic vascular anomalies (Grada and Phillips,

Tisaire, J., Rodrigo, E., Ribeiro, S., Ricci, M., Cuellar, J., Zeugolis, D., Bayon, Y. and Rocha, I.

Concept Design of a New Portable Medical Device for Lymphedema Monitoring: A EIT Health ClinMed Summer School Project.

DOI: 10.5220/0007696706110620

In Proceedings of the 12th International Joint Conference on Biomedical Engineering Systems and Technologies (BIOSTEC 2019), pages 611-620

ISBN: 978-989-758-353-7

611

2017). Secondary lymphedema is acquired and arises

because of an underlying systemic disease, trauma or

surgery (Kayiran et al., 2017).

Women who have undergone surgical or radiation

treatment for breast cancer, the most prevalent cancer

among women, are at a lifelong risk of developing

lymphedema. Some studies report an incidence of

lymphedema of 42% among the breast cancer

survivors (Norman et al., 2009). Lymphedema is a

significant problem in developing countries. It has

been reported that lymphedema affects as many as

200 million people worldwide and approximately 3

million people in the United States (Rockson and

Rivera, 2008).

The condition may result in physical and

psychological consequences, which can negatively

impact a woman's quality of life and compromise her

emotional well-being. It limits the range of motion, as

well as causing feelings of pain, heaviness, and

numbness. Psychologically, women may have

decreased self-confidence due to a disturbance in

body image, and experience negative emotions such

as anxiety, frustration, sadness, anger, and increased

self-consciousness (Taghian et al., 2014, Torres

Lacomba et al., 2010).

Lymphedema usually progresses through four

stages. At Stage 0, lymphatic flow is disturbed but

there is no apparent edema in the extremities; it is

possible to notice a difference in feeling, unusual

tiredness, or slight heaviness. At Stage 1, the

circumference of the extremities has increased but the

edema recedes with elevation because the skin and

tissues haven’t been permanently damaged. At Stage

2, the edema does not recede with elevation and may

present as pitting or nonpitting. Finally, at Stage 3 the

affected limb becomes very large and misshapen due

to the irreversible fluid collection(International

Society of Lymphology, 2003).

There is no cure for lymphedema. Treatments are

designed to reduce the swelling and the other

symptoms. The treatments include non-surgical

(complete decongestive therapy (CDT), compression

therapy, advanced pneumatic compression pumps

and exercise) and surgical options (physiological and

reductive methods), as shown in Table I.

These treatments, however, are only effective at

an early-stage of lymphedema (Kayiran et al., 2017,

Norman et al., 2009).

Therefore, it is essential to diagnose the condition

as soon as possible to prevent or minimize its

progression with the appropriate treatment (Network,

2011, Stout et al., 2012). Nowadays there are several

methods to diagnose lymphedema, however, most

cases arise after the symptoms are visible meaning the

disease is already at an advanced stage that could

become irreversible.

Recent research developments suggest that new

methods capable of detecting the underlying

deficiencies of the lymphatic transport system could

create a future where it is no longer necessary to wait

for the patient’s symptoms to become severe enough

to be detected. Although some of these methods are

already available in the market, they are far away to

become the new gold standard mainly due to its price.

Table 1: Lymphedema treatments.

Non-surgical treatments

Surgical treatments

Complete decongestive

therapy

Reductive techniques

Manual lymph drainage

Direct excision

Compression therapy

Liposuction

Exercise

Physiological techniques

Skin care

Lymphatic-lymphatic by-

pass

Compression garments

Lymphatic-venous by-pass

Advanced pneumatic

compression therapy

Lymph node transfer

Laser therapy

The quality of life of affected people would

increase considerably with an early diagnosis and

diligent care of the affected limb.

3 STATE OF THE ART

As mentioned previously, lymphedema should be

diagnosed as soon as possible. The goal of timely

intervention for breast cancer-related lymphedema is

decreased edema, smaller limbs, reduced joint aches,

muscle pain and tightness, decreased infection rates,

heightened patient desire to continue treatment,

decreased medical costs, and improved quality of life

(Soran et al., 2014). A delayed diagnosis or treatment

can result in rapid and unchecked progression of the

disease leading to complications, lack of mobility,

loss of function and disability, often leading to costly

emergency room visits and treatment (O'Toole et al.,

2013). It has been proved that progressive action can

diagnose lymphedema four times earlier compared to

the current diagnosis procedure (Soran et al., 2014,

Shih et al., 2009, Brunelle et al., 2015). To sum up,

the challenge facing clinicians is that there is no

reliable, affordable diagnostic capable of detecting

the disease before symptoms of lymphedema

develop.

Nowadays lymphedema diagnosis is made in a

clinical environment by thorough evaluation and

physical examination, by assessing volume and shape

ClinMed 2019 - Special Session on Designing Future Health Innovations as Needed

612

discrepancies and skin changes among the extremities

(Tahan et al., 2010, Kim et al., 2016). Volume

measurements can be done by including

circumferential measurement of the limbs with a non-

flexible tape, water displacement or perometry. The

perometry works similarly to computer-assisted

tomography, but uses infrared light instead X-rays

(O'Toole et al., 2013). Unfortunately, these methods

do not provide objective data about the localization of

the edema or the shape of the extremity, they are time-

consuming, difficult to perform and require

considerable experience from the clinician. They may

be difficult to use in individuals with large, loose skin

folds or in those with arthritis who cannot extend their

limbs.

New diagnostic approaches include non-invasive

measurements (tonometry, bioimpedance

spectroscopy) and imaging techniques

(lymphoscintigraphy, ultra-sonography, computed

tomography, and magnetic resonance imaging)

(Kayiran et al., 2017).

A tissue tonometer evaluates the tissue resistance

to compression. It can be used to assess the skin

pliability and fibrosis during lymphedema treatment.

While tissue dielectric constant can measure skin

texture and resistance, imaging techniques are able to

show the presence of extra fluid within the tissues

(Liu and Olszewski, 1992, Mayrovitz, 2009),

however they are expensive and inefficient. A

commercially available technology that use tissue

dielectric constant measurements is LymphScanner

by Delfin Technologies (Technologies).

Bioimpedance spectroscopy (BIS) is a non-

invasive technique that was first used by nutritionists

to assess body composition and has been used

recently as a reliable in early-stage diagnosis

technique of lymphedema since it assesses the

extracellular fluid compartment before visible

changes have settled (Cornish et al., 2001). BIS

involves applying a small electrical current at

frequencies ranging from 1-20 kHz to 1MHz through

the body and measures the opposition to the flow of

this current (defined as impedance). The electrical

current is primarily conducted by the water

containing fluids in the body; this water is contained

both within the cells, intracellular water, and external

to the cells, extracellular water. At low frequencies,

current passes through the extracellular fluid (ECF)

space and does not penetrate the cell membrane,

characterized by the theoretical resistance at zero

frequency (𝑅

). At high frequencies, however, the

current passes through both the intracellular fluid

(ICF) and ECF. Using this principle, a value of

impedance can be calculated. The measured

impedance is inversely proportional to the amount of

fluid (Erdogan Iyigun et al., 2015). An early report of

the use of this technique was published in 1996 where

it was shown that BIS technique is significantly more

sensitive than circumferential measurements and able

to detect small differences in the extracellular

volumes between the extremities of a patient (Cornish

et al., 2001). Recently, it has been shown that BIS

predicted the onset of lymphedema 10 months before

the condition could be clinically diagnosed, meaning

before there were visible symptoms (Erdogan Iyigun

et al., 2015).

Currently the existing commercially available

products using BIS as a diagnostic tool are

Lymphedema index (L-Dex) (Impedimed) and

SOZO® (SOZO) by Impedimed. A prospective

observational study demonstrated the impact of L-

Dex® measurements where it reduced the incidence

of clinical lymphedema from 36.4% to 4.4% in a

clinical practice (Soran et al., 2014). However, these

devices are costly and not portable. Only the most

specialized rehabilitation centres have access to

equipment that use BIS to obtain a more accurate

monitoring of the progression of lymphedema.

Performing the surveillance only at the hospital and

with big intervals between the check-ups leads to late

diagnosis and often lymphedema detection might be

done at an irreversible stage.

4 DESCRIPTION OF THE

DEVICE

Non-invasive regular patient monitoring in home

environment presents a high interest in healthcare

today. To follow regularly the patient’s health state, a

portable measurement device which is compact, low

cost, low power, and capable of performing

measurement with adequate accuracy is highly

desirable both for hospital and home use.

In this paper it is proposed a portable home-

monitoring device for early diagnosis of lymphedema

following breast cancer surgery. The device is

intended to be used regularly to monitor the patient

and detect in time the lymphedema.

The system, shown in Figure 1, comprises a BIS

device and a mobile application. The device includes

two adjustable bracelets, a belt and a

recording/controller module. Each bracelet includes

an active electrode for delivering AC current and a

passive electrode for performing impedance

measurement and an inertial measurement unit (IMU)

to measure the accelerations. The belt includes an

active electrode and a passive electrode.

Concept Design of a New Portable Medical Device for Lymphedema Monitoring: A EIT Health ClinMed Summer School Project

613

Figure 1: Detailed scheme of the operation: bioimpedance data, acquired by the wearable device, are transferred by Bluetooth

to a mobile phone application. After data analysis, biofeedback is sent to the patient and the clinicians. The device includes

two bracelets, a belt and a recording/controller module. Each bracelet includes an active electrode, a passive electrode and an

IMU. The belt includes an active electrode and a passive electrode.

The recording/controller module is designed to

send multi-frequency signals through the limbs, to

record the output and to process the signal to calculate

the lymphedema risk. The whole device is meant to

be portable using an internal rechargeable battery

encased into the recording/controller module.

To perform the upper limbs impedance

measurements, the user must wear the bracelets over

the wrists and the belt over the chest as shown in

Figure 2a. To perform the lower limbs impedance

measurements, the user must wear the bracelets over

the ankles and the belt over the hips as shown in

Figure 2b.

Figure 2: Electrodes’ positions to perform a measurement

with the device. For upper limb measurement (a), the

current passes from the wrist to the chest. For lower limb

measurement (b), the current passes from the ankle to the

hips.

Each limb is assessed separately by sending the

AC current from the belt to the bracelet by means of

active electrodes.

To avoid wrong measurements affected by

motion artefact the bioimpedance measurements are

only taken place once the level of activity measured

by the IMU is low. The bioimpedance measurements

are then stored to the memory card and sent via

Bluetooth module to the mobile phone.

The mobile application will provide the access to the

measured data, stored via Cloud, to the user. The app

will send notifications to remind the user to take the

measurement and alert the patient for increased risk

of developing the lymphedema.

4.1 Technical Requirements

The solution must: (1) provide multi-frequency

currents between two points located at the extremes

of the body parts of interest; (2) measure the related

bioimpedance and (3) store the measurements in a

flash memory and send them via Bluetooth module to

the mobile phone.

In addition, to avoid high signal noise by motion

or physical activity the bioimpedance measurements

can only take place once the activity level measured

is low. Therefore, an accelerometer sensor is included

as a technical aspect to control the measurement

process.

The schematic of our bioimpedance measurement

device is shown in Figure 3.

As said, in bioimpedance measurement system, a

small AC current passes through the body and the

opposition to the flow of this current (defined as

impedance) is measured. To achieve a suitable

accuracy is necessary that the output current is stable

and within safe magnitudes for a wide bandwidth.

For patient safety, a maximal AC-current of

0.5mA and frequency range between 1 kHz and

1MHz must be adopted.

Moreover, to keep the output current stable over

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614

Figure 3: Schematics of the bioimpedance measurement device.

the frequency range independently of load changes,

the output impedance should be maintained higher

than the load impedance, so that the major part of the

current is given to the output and the inner losses of

the source are reduced.

4.2 Hardware

The recording/controller module includes a signal

(sine wave) generator, a voltage controlled current

source (VCCS), two identical instrumentation

amplifiers, a Gain Phase Detector (GPD), an

Analogue Digital Converter (ADC) and a

microcontroller unit (MCU). The battery needed for

the system, is a common rechargeable of 5V.

The signal generator and the VCCS generate a

sinusoidal current at pre-programmed frequencies in

the range of 1 kHz to 1 MHz. The amplified voltage

drops across the tissue and the reference resistor Rs,

are fed into the GPD which outputs two voltages

proportional to their magnitude’s ratio and phase

difference, respectively. The gain and the phase

extracted are used to compute the impedances at each

frequency and then the values are displayed on the

screen, sent to Bluetooth module and stored in on-

board memory by MCU.

As mentioned in the requirement section, the

accuracy and conformity of the excitation current can

affect the quality of the measurements and also the

safety of patients. Therefore, the VCCS block plays

an important role in the design.

A high-performance current source for portable

bioimpedance spectrometer should have high

bandwidth, high output impedance over the chosen

frequency range, and stable and safe injected current

lower than 0.5mA.

Different topologies of VCCS have been

proposed such as current conveyors, Howland current

source or Tietze current source (Bragos et al., 1994,

Tietze et al., 2014, Horowitz and Hill, 2015).

Among the available configuration, we opted for

the modified version of the Howland current source

proposed by P. Horwitz and W. Hill (Horowitz and

Hill, 2015) and showed in Figure 4.

Figure 4: Modified Howland current source.

In this version of the circuit all four resistors in

the positive and negative feedback lines have equal

values, so the circuit works without any

amplification. The load current depends only on input

voltage and value of current forcing resistor RI and is

independent of the load resistance. To ensure a stable

and accurate voltage controlled current source the

operational amplifier should be selected carefully. In

particular, amplifier with high common mode

rejection ratio (CMRR), low input voltage noise and

acceptable wide bandwidth are preferred.

Concept Design of a New Portable Medical Device for Lymphedema Monitoring: A EIT Health ClinMed Summer School Project

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In order to verify the operation of the selected

circuit, computer simulation was per-formed with

Cadence

Pspice

Lite 16.6. The AD8021

operational amplifier was selected for its high low

input voltage noise (2.1 nV/√Hz) and wide bandwidth

(490 MHz). The current source was designed to

deliver sinusoidal current of maximum amplitude 150

µA for 0.6 V of input voltage, so the RI in this circuit

is 4 kΩ. Figure 5 shows the results of the output

current and output impedance of the circuits in

frequency domain varying the load impedance value

) from 100 Ω to 5 kΩ.

Figure 5: (a) Output current of VCCS for RL=100 Ω, 1 kΩ,

2 kΩ, 3 kΩ, 4 kΩ, 5 kΩ. (b) Output impedance of VCCS.

The measuring block comprises two

instrumentation amplifiers with high bandwidth and

high CMRR and a gain phase detector.

The GDP was chosen because it is fast in

measurement and simple in design as compared to

bridge method (Steendijk et al., 1993) or the

quadrature demodulation method (Pallás-Areny and

Webster, 1993). It measures the gain and phase

difference of two signals as voltage outputs. AD8302

from Analog Devices is chosen as GDP. The outputs

of GDP are feed into ADCs of the microcontroller

system. Also, the accelerometer’s signal from IMU is

sent to MCU.

4.3 Software

The signal processing takes place in the MCU. The

microcontroller system performs different tasks with

the on-board components. It interfaces with the signal

generator sweeping the frequencies, calculates the

impedances from the signals of the GDP, displays the

results on LCD screen, stores them on a FLASH

memory and sends them through Bluetooth to the

smartphone, which stores the measurements in a

cloud server.

Every 5 sec the total energy, which correspond to

the activity level, is computed from the raw

accelerometer signal. If the energy is below the fixed

threshold, the MCU initiate the bioimpedance

measurements.

The gain and the phase extracted from GPD are

used to compute the impedance at each frequency.

The last part of analysis is done by the mobile

phone since requires a higher computational cost.

The impedance data are used to predict the

impedance at zero and infinite frequencies that cannot

be measured directly. As mentioned before, the

impedance at zero frequency (R

) represents the

extracellular water (ECW) compartment while the

impedance at infinite frequency (R

∞

) represents the

total tissue water. Thus, the impedance at zero

frequency is a measure of the water volume, including

lymph. To derive the intracellular fluid (ICF) instead

the following formula is used:

· R

∞

− R

∞

(1)

and R

∞

are computed using the Cole model

(Kyle et al., 2004).

Different methods have been used to assess

lymphedema with bioimpedance measures. However,

none of these provides an absolute measure of

lymphedema but rather a comparison of the affected

limb with that of the unaffected one (Cornish et al.,

2001, Erdogan Iyigun et al., 2015, Ward et al., 2011).

Clearly, there are some cases in which the

lymphedema presents in both limbs where this

approach cannot be used.

Therefore, the approach implemented in our

device is double. Instead of comparing the two limbs

at the same time, a measure of the patient at the time

of diagnosis, prior to surgical intervention can be

stored providing a baseline for computing the ratio.

This allows for the natural asymmetry that patient

may have between their arms to be accounted and

detect the bilateral lymphedema as well.

ClinMed 2019 - Special Session on Designing Future Health Innovations as Needed

616

Alternatively, if the measure at baseline is not

available, the ratio 𝑅

/𝑅

𝑤

can be computed. In fact,

the intracellular fluid volume is not affected by

lymphedema since it is an accumulation of an

extracellular fluid. A previous study has shown that

this ratio differs significantly (Ward et al., 2011).

Independently by the method used to calculate the

ratio, the incoming measure is compared to the stored

baseline to provide an alert to the user when it

exceeded the threshold. As reported in other studies,

the criterion indicative of lymphedema is set at the

mean +3 standard deviation of the control population

(Erdogan Iyigun et al., 2015, Cornish et al., 2001,

Ward et al., 2011).

The smartphone application will also show the

trends of the bioimpedance measurements.

4.4 Consideration about Usability, Risk

Analysis and Essential

Requirements

The intended use of our device is to monitor the

limb’s volume through bioimpedance. The target

users are the population that have undergone breast

cancer surgery, at risk of developing lymphedema.

The usage involves the examination of parts and

battery status of the device, the placement of the

sensors and the disposition into resting position. The

resting position requires the patient to sit

comfortably, stay awake but relaxed and to extend

his/her arms on a medium-height table. Prior to the

bioimpedance measurement, a 1-minute stabilization

period is held on. The measurements take 10 minutes

to be carried out during which the patient must stay

relaxed in the resting position. As well, consistency

among measurements is required.

The device we proposed is a result of a design

process, where consideration about the wearability,

electrodes position and easy-to-use were considered

in light of unsupervised environments use.

Figure 2 represents the intended position of the

electrodes since lymphedema commonly appears in

the limbs. The bracelets and the belt are adjustable

and made with Velcro in order to provide a general

solution for fitting people of different sizes, without

influencing the comfort by tightness.

To ease the system setup and improve usability,

before the start of the measurements, a tutorial is

shown to the user to inform about the correct use and

position of the device. The interface also provides the

automatically check of the correct skin contact.

The identification of hazards derives from the

known and foreseeable hazards associated with the

medical device in both normal and fault conditions.

The hazards have been categorized into the following

groups:

 Energy hazards: electrostatic discharge and

external electromagnetic fields influence, metallic

implant in region of measurement, electric

implant/pacemaker, burn due to external tattoo in

the evaluation area.

 Biological/chemical hazards: pregnancy,

irritation of skin due to previous lesion, usage

during coagulant/anticoagulant medication.

 Operational hazards: lesion due to difficulty to

adapt sensors, irritation due to pressure, humidity

and/or temperature, contact with liquids during

normal use.

 Information hazards: misuse due to incomplete

instruction, labelling or packaging.

The assessment of acceptability is based upon the

criteria for the acceptance of the combinations of

harm probability and harm severity. A semi-

quantitative risk evaluation matrix is presented in

Annex Table 1 along with the definitions of

occurrence probability levels of hazards and harm

severity.

5 FROM CONCEPT TO

PRODUCT

As is well known, the translation of novel ideas into

a product faces many challenges. The idea must be

aligned both with the clinical and market needs. It is

therefore essential to establish if the product meets

the unmet needs and that there is a clear path to

penetrate the market.

Lymphedema is a significant problem, that affect

3-5 million of Americans and 4 million people in

Europe, where three-quarters of lymphedema cases

are at stage 0 and 1, that is more than ALS, Cystic

Fibrosis, Multiple Sclerosis, Muscular Dystrophy,

and Parkinson’s Disease combined. Moreover, only

in early-stage lymphedema, the conservative

treatment has been shown to be effective. Thus, there

is a clear clinical need.

From the economic prospective, the early

intervention reduces the need for intensive

rehabilitation and it costs five times less. According

to the International Lymphedema Framework, the

financial impact of lymphedema in Europe is about

€4 billion in loss of earnings, close to 1 billion € in

health and social welfare bill and about 2 billion to

treat cellulitis (International Lymphedema

Framework). Shih et al (Shih et al., 2009) found that

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the 2‐year mean costs for women with lymphedema

were a significant $23,167 higher than for patients

with breast cancer without lymphedema. Stout et al.

(Stout et al., 2012) reported that the cost to manage

early-stage lymphedema is $636.19 vs. $3,124.92 per

patient per year in the more advanced stages,

requiring intensive therapy.

This means that for the healthcare payers’ point

of view, less associate cost; for the patients, an

increased quality of life and for the clinicians’

perspective, a deeper understanding of the

phenomenon and reduced time for the visits.

Options regarding funding have being explored

and structured around a combination of grants, loans,

investors and equity shares. Given the social impact

of breast cancer and the prevention of an associated

chronic condition, a crowdfunding campaign could be

expected to obtain funding to a certain extent.

The development plan for the product presented

in this paper can be summarized in: data acquisition,

data extraction, software component. Data

acquisition mainly involves the design of the

hardware that will achieve a proper acquisition of the

measurements, good usability and testing. Data

extraction concerns the validation of optimized signal

processing. Software component involves the design

of easy-to-use mobile application.

The design reviews will take place throughout the

product development process to evaluate the design

against technical specifications, small- and large-

scale manufacturing, risk assessment and usability.

Throughout the development, interviews on the

design of the device with professionals and patient

associations will be performed from the early stages

to the market launch.

An important milestone is obtaining the proof of

concept that will demonstrate the effectiveness, safety

and usability of the device. This involves the in vitro

testing, side by side testing with other BIS devices,

pilot clinical trial, usability and acceptability studies

with both patient and healthcare providers.

Once a functional device has been developed the

next logical step would be to obtain clinical

validation, regulatory approval, IP protection and

finally scalability and launch.

6 DISCUSSION

The device presented in this paper is the first medical

device that permits accurate monitoring of

lymphedema progression by the user.

In addition to the time needed for medical

appointments, other solutions require the acquisition

of expensive equipment and/or certain level of

medical expertise and have to be used at the hospital.

Measurement of limb volume with water

displacement can be cumbersome and difficult to

perform in the physician’s office; circumferential

measurement of limb volume using a tape is

unreliable; the use of infrared perometry is limited by

the fact that the equipment is not portable and requires

individuals to come into a clinic. BIS, instead, is a

direct measurement of extracellular fluid volume.

This technique has been studied as a tool to detect

early signs of subclinical lymphedema. The existing

commercially products using BIS as a diagnostic tool

are costly, not portable so they are available only in

specialized rehabilitation centres. The capital cost of

the L‑Dex U400, SOZO® is £7,500 £8,000 per unit

respectively and can be used only by trained nurse or

physiotherapist, as a part of routine screening.

The solution presented is easy to implement and

affordable to patients

The method proposed for the measurements can

be applied to every part of the human body

independently of anatomical characteristics of

specific individuals (e.g. body weight, size, etc.).

The risk analysis shows that any potential damage

is very unlikely thus making the operation of the

device safe for individual use without any

surveillance or support.

Future usability and acceptability studies should

be performed involving patients in order to optimize

the interface between the device and the user.

All the added values of this new design make it a

highly competitive solution compared to all existing

alternatives.

ACKNOWLEDGEMENTS

The authors would like to thank all the organizers of

the EIT Health ClinMed 2018 summer school.

Without them this project would have never born.

Special thanks for all the mentors who helped us

to improve and better define this work.

The authors would also like to thank the

Rehabilitation service at the Hospital Santa Maria

(Lisbon, Portugal) and the Pediatric Cardiology

department at the Hospital Santa Marta (Lisbon,

Portugal) for hosting and enables us to have a broader

view of the different healthcare providers which

allows us to implement all this knowledge to design a

better solution.

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618

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ANNEX

Table 2: Semi-quantitative risk evaluation matrix. In red, the unacceptable residual risks and not allowed usage for those

risks’ conditions.

Risk Severity Frquency Control measures

Irritation due to pressure, temperature

and/or humidity

Minor Occasional -

External electromagnetic fields influence Negligible Remote -

Electrostatic discharge Minor Remote

Make sure the patient is not touching

metal and that there is no skin-skin

contact

Contact with liquids during normal use Serious Remote

Specify avoidance of liquids near the

sensors in the instructions of use

Usage during coagulant/anticoagulant

medication

Catastrophic Improbable -

Lesion due to difficulty to adapt sensors Minor Probable

Reevaluation of the instructions and

adjustable sensors

Mismeasurement due to difficulty to adapt

sensors

Minor Probable

Reevaluation of the instructions and

adjustable sensors

Incorrect skin contact Minor Probable

Alert message to rearrange the sensors

of the device

Metalic implant in region of measurement Serious Probable

Useage not allowed in the region where

there is a metallic implant

R10

Misusage due to incomplete instructions Serious Occasional

Reevaluation of the instructions of use

with patient and doctors feedback

R11

Burn due to external tattoo in evalution area Serious Occasional

metallic tattoos, usually older, in the

region of evaluation are banned

R12 Usage during pregnancy Catastrophic Remote Usage not allowed during pregnancy

R13 Patient has an electric implant/pacemaker Catastrophic Occasional

Usage not allowed in the presence of

pacemakers

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