PAIN AND EFFICIENCY IN NEONATAL BLOOD SAMPLE

SCREENINGS

New Devices for Reducing Pain and Improving Blood Sample Quality

Bruno Wacogne, Christian Pieralli

Institut FEMTO-ST, Département d'Optique P.M. Duffieux, UFR Sciences et Techniques

Route de Gray, 25030 Besançon cedex, France

Gonzalo Cabodevila, Nolwenn Baron

Institut FEMTO-ST, Département MN2S, Avenue de l'Observatoire, 25030 Besançon cedex, France

Sandrine Marioli

Service de Pédiatrie 1, CHU Saint Jacques, 2 place Saint Jacques, 25030 Besançon cedex, France

Lionel Pazart

Centre d'Investigation Clinique en Innovation Technologique,CHU Saint Jacques

2 place Saint Jacques, 25030 Besançon cedex, France

Keywords: Neonatal screening, pain evaluation, micro-needles arrays, image processing.

Abstract: Neonatal blood sample screening is recognised as a difficult gesture and painful to the newborns. The

number of detected diseases is still relatively low and depends on the country where it is performed. There

is a real need for new techniques that reduce pain, facilitate the blood sampling, increase the quantity of

sampled blood and improve the collection of blood of the cardboard blotter actually used. In this paper, we

present systems that are currently developed in Besançon (France) in collaboration between the FEMTO-ST

Institute and the University Hospital. They mainly concern micro-needles arrays and pressure free blood

sampling devices. The choice of these systems has been dictated by a study of the pain that newborns feel

during the gesture. The ulterior motive of this work is to improve neonatal blood sample screenings and

therefore, to increase the number of screened diseases and try to generalise this technique to places where it

is not yet done.

1 INTRODUCTION

The blood sample screening of several congenital

diseases (phenylketonuria, hypothyroidism, adrenal

hyperplasia, ...) is performed routinely at birth in

many countries. The number of detected diseases

depends on the screening policy of the country and

the technical limitations of the methods. For

neonates, techniques are mainly limited by the

difficulties of realisation of the sampling gesture, the

small volume of punctionable blood and the pain

caused by the gesture. Currently, the French

Association for the Detection and Prevention of

Handicaps for Children (AFDPHE), responsible for

organising the screening in France, favors (at the

third day of life) a collection of capillary blood after

a bite by a retractable lancet at the heel of the

newborn. This gesture is followed by successive

pressures on the heel in order to collect blood

droplets on a cardboard blotter. This gesture is

recognised as painful (Facchini, 2005), (Owens,

1984). It should be noted that in some places,

screenings are performed with venous blood instead

of capillary blood. In this case, the gesture is more

technical and it presents risks for both the nurse and

the newborn. In this paper, we restrict the discussion

to the case of capillary blood.

290

Wacogne B., Pieralli C., Cabodevila G., Baron N., Marioli S. and Pazart L. (2009).

PAIN AND EFFICIENCY IN NEONATAL BLOOD SAMPLE SCREENINGS - New Devices for Reducing Pain and Improving Blood Sample Quality.

In Proceedings of the International Conference on Biomedical Electronics and Devices, pages 290-295

DOI: 10.5220/0001776902900295

 SciTePress

The orientation of the present works is intended

to develop medical devices less painful and that

offer a higher potential screening of a larger number

of diseases in newborns, replacing technology

currently used.

The context of the study, together with the

evaluation of pain during the blood collection

gesture is presented in section 2. Section 3 deals

with the study of a painless micro-needles array

meant to replace the classical lancet. In section 3, we

present a device developed to obtain blood without

successive pressures on the newborn's heel.

Furthermore, this system can be used to efficiently

deposit the collected blood on the cardboard blotter.

Then, a conclusion and some perspectives will be

proposed at the end of this manuscript.

2 CONTEXT AND PAIN

EVALUATION

Screenings are achieved by nurses on the third day

of life. They require the use of an automatic, sterile

and disposable lancet that pierces the skin of the

heel. The heel is then pressed to obtain droplets of

blood that are collected on circles drawn on a

cardboard blotter (as seen on figure 1). Since the

blood flow is not sufficient, successive manual

pressures to the heel are required. Circles on the card

must be completely filled and the blood must cross

the card (this is not the case for all the circles in

figure 1). If the first attempt does not give enough

blood, a second is made on the same heel or on the

other one. In the same way, if the droplets do not

cross the screening card it is necessary to add blood.

This tracking is recognised as painful.

Newborns feel more or less pain during the

blood sampling gesture. Pain can be estimated using

various behavioural scales (Destuynder, 1991),

(Uyan, 2008). Both D.A.N. (Douleur Aiguë du

Nouveau-Né, Newborn Intense Pain ) and E.D.I.N.

(Echelle de Douleur et d’Inconfort du Nouveau-Né,

Newborn Pain and Discomfort Scale) scales are

adapted to the evaluation of newborn's pain. We

used the D.A.N. scale because it is more specific to

intense pain. It allows quoting three criteria: the

facial answer, the movements of the members and

the vocal answer. Each criterion is quoted either

between 0 and 3 or between 0 and 4. We evaluated

the pain at five different moments: before the

gesture, when the nurse takes the baby's heel, during

the lancet sting, when the nurse presses the heel and

after the gesture.

For a first analysis, we observed 55 children for

which 58 stings were needed. Indeed, no blood was

obtained in 3 cases at the first attempt.

Figure 1: Actual blood sampling technique (top) and

cardboard blotter used to collect blood.

The gesture proving to be painful for a majority

of children, we refined our study at three moments:

the taking of the heel, the sting, the pressing of the

heel. The results obtained showed that the taking of

the heel is not painful (only 1 case). The sting is

painful in 10 cases, what nearly represents 25 % of

the cases. The pressing of the heel is the most

painful moment (26 cases representing 68%).

Therefore, we oriented our works toward two

new systems of blood sampling. The first one is a

micro-needles array meant to reduce the pain during

the sting (in replacement of the lancet). The second

one is used after the heel has been stung with the

lancet. It is designed to collect enough blood without

any pressure on the heel. Moreover, this system

leads to a perfect impregnation of the cardboard

blotter.

3 MICRO-NEEDLES ARRAY

The goal of this work is to estimate the geometry a

micro-needles array used to collect blood at the

newborn's heel. This array should replace the lancet.

The goal is to penetrate the newborn's heel and to let

blood flow in the holes of the micro-needles by

capillarity. In a final version, a tank should be

designed to store the sampled blood. Various studies

concerning micro-needles have been published, but

PAIN AND EFFICIENCY IN NEONATAL BLOOD SAMPLE SCREENINGS - New Devices for Reducing Pain and

Improving Blood Sample Quality

291

very little on blood collection. For example, we can

mention the work presented by (Mukerjee, 2004). In

this case, a liquid is obtained after a relatively long

time but this liquid does not contain only blood.

Other systems, inspired by mosquitos morphology,

are presented but some complementary studies are

still required (Oka, 2001), (Sharaf, 2003). Figure 2

shows an example of a micro-needles array

fabricated in our laboratory. This particular

architecture was designed for drug delivery and not

for blood sampling.

Figure 2: Example of micro-needles array fabricated in our

laboratory.

For our specific application, the characteristics

of the micro-needles have to be rethought according

to the newborn's heel anatomy. The characteristics

we studied are the shape, the dimensions and the

number of micro-needles in a array. This work is

based on a capillaroscopy study of the newborn's

heels that helped to define the depth of the children's

capillary network (350 µm) and its density (70

capillaries by mm

). In what follows, we present the

conclusion drawn from our studies. The details of

numerical simulations can be obtained on demand.

Some parameters used in this study come from

the work conducted for several years in our

laboratory. Micro-needles are fabricated with

silicon. The silicon surface is oxidized in order to

make the device bio-compatible. The needles are

cylindrical. In order to improve their strength the

basis of the needles is conical. The tip of the needles

is bevelled in order to facilitate the penetration of the

stratum corneum. Finally, the needles exhibit a

longitudinal slit. It is used to maximize the contact

surface between the capillaries and the hole of the

needle. Figure 3 shows a schematic diagram of one

micro-needle.

Figure 3: Schematic representation of a micro-needle

dedicated for newborns blood sampling.

3.1 Dimensions of the Needles

The height L of the needles is fixed to 1200 µm to

ensure a penetration until the dermis of skin. The

inner and outer diameters (D

and D

) are 60 and 150

µm respectively. These diameters increase the

probability to meet a capillary.

The bevel exhibits an angle α = 41°. This value

is calculated considering that a third of the needle

penetrates the skin (400 µm) and that the hole of the

needle must be at the level of the capillaries (350

µm).

The slit must not extend outside the area where

the capillaries are located. In this way, we reduce the

risk to collect something else than blood. Its length

is therefore limited to L

= 200 µm. The width of the

slit doesn't have an influence on the needle strength.

Numerical simulations showed that the Von Mises

constraints are almost not influenced by this

parameter. For the moment, we consider a slit width

of 60 µm.

The basis of the needle is conical. This cone is

defined by its height H and its angular aperture β.

Numerical simulations showed that the Von Mises

constraints are minimized for a height H = 600 µm

and an angular aperture β < 30°.

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3.2 Probability to Collect Blood with

the Needles

To summarize, the micro-needles are cylindrical

with a conical basis. They exhibit an opening used to

collect blood. This opening consists of the hole of

the needle and the longitudinal slit. When the micro-

needle has penetrated the skin, two surfaces can be

defined: the total surface of the needle in skin and

the surface of the opening that is susceptible to be in

contact with the capillaries. The ratio between these

two surfaces allows estimating the probability to

collect blood.

Studies showed that an array of 8 needles gives a

probability to collect blood equal to 67%. It is

necessary to increase the number of needles up to 24

to reach a probability of 96%. We consider that the

distance between two needles must be at least equal

to 1 mm. Below this size, the needles may not

penetrate the skin (fakir effect). Therefore, a 24

needles array is about 4*6 = 24 millimetre square,

which is quite large. Another possibility is to use a 8

needles array (8 millimetre square) three times on

three different parts of the heel.

3.3 Perspectives

To conclude this section, we have to mention that

we are actually working on capillarity studies that

should answer the question: how long will it take to

collect enough blood ? It is indeed possible that a

pumping system will be required in order to reduce

the gesture duration.

Another aspect that must be addressed concerns

the penetration of the needles into the skin.

Techniques developed in the frame of other projects

should be transposable to the specific anatomy of

newborn's heel.

4 PRESSURE FREE

COLLECTION SYSTEM

We recall that most of the children feel pain when

their heel is pressed. The pressure on the heel is

necessary to get the required quantity of blood in

order to correctly fill the circles of the cardboard

blotter. There are two main difficulties:

1. the quantity of the sampled blood with respect

of the felt pain

2. the impregnation of the card circles; blood must

cover the whole surface of the circles and the

rear face of the card must be correctly

impregnated.

To bring some solutions to these two constraints,

a particular tip is studied (figure 4). This tip is fixed

to the extremity of a reversed syringe that is not

represented on the figure. The tip consists of a

transparent bell onto which a micro-grid is stuck. A

flexible interface is fixed on the micro-grid. The

latter must be removable. It consists of thick disc

with an aperture in its centre. We proceed as

follows.

Figure 4: Principle of the pressure free system.

1. We pierce the newborn's heel with the

conventional lancet.

2. We apply the device onto the cut. The flexible

interface ensures the bloodproofness of the

whole system and prevents the skin to be in

contact with the micro-grid. Without this

interface, the probability that the cut coincides

with a few micro-apertures of the grid would be

very weak and the quantity of sampled blood

likely insufficient.

3. We start the aspiration by means of the reversed

syringe. The pressure on the heel is no longer

required.

4. Blood fills the transparent bell. The volume of

the bell is fixed to 1 ml. We stop the aspiration

when the bell is filled.

5. We withdraw the device from the heel.

6. We remove the interface. The dimension of the

grid apertures is calculated so that blood

remains in the bell during these operations.

PAIN AND EFFICIENCY IN NEONATAL BLOOD SAMPLE SCREENINGS - New Devices for Reducing Pain and

Improving Blood Sample Quality

293

7. We apply the tip on the card. The apertures of

the grid fill the whole surface of the circles

printed on the card. By stamping, the circles are

correctly filled. The capillarity forces are

sufficient for blood to distribute efficiently.

Grids are micro-machined by Deep Reactive Ion

Etching. Three characteristic dimensions of the

apertures have been considered: 300 µm, 200 µm

and 75 µm. Two grid thicknesses have been tested:

300 µm and 525 µm.

The results presented here only concern the tests

of homogeneity of the blood deposited on the cards.

The blood aspiration through the grid will be tested

subsequently. An example of grid attached to the

transparent bell is shown in figure 5.

Figure 5: View of a micro-machined grid fixed on a

transparent bell.

We analyzed the uniformity of the blood

collection with the help of a light source equipped

with a diffuser that permits to illuminate the

cardboard blotter in a homogeneous manner. A CCD

camera is used to acquire pictures of the different

blood impregnated circles. Finally, a suitable image

processing is used to measure the uniformity of

blood. An example of impregnated card is presented

on figure 6 (top). In this case, only 800 µl was

necessary to completely fill the circles. Besides, no

pressure on the syringe was required, the capillarity

forces being sufficient. The homogeneity of the

blood is clearly observed. Also, we can note that

blood completely crosses the card as it can be seen

in figure 6 (bottom). In all, six cards have been

impregnated with grids of different thicknesses and

apertures of various dimensions.

Two steps are required to evaluate the

homogeneity by image processing. The first one

consists in semi-automatically detecting the circle

that contains blood. The second one consists in

evaluating the homogeneity of the blood. To do this,

the pictures are convolved with a test window of 5x5

then of 25x25 pixels. We calculate the standard

deviation on the considered window; the lower the

standard deviation, the better the homogeneity. A

typical result is given in figure 7 where the

homogeneities obtained with apertures of 300 and 75

µm are shown. In abscissa we have the number of

the card and in ordinates the value of the

homogeneity indicator.

Figure 6: Picture of both front and rear side of a cardboard

blotter impregnating with the pressure free device.

Figure 7: Experimental estimation of the homogeneity of

the cardboard blotter impregnation for two aperture sizes.

The conclusion seems obvious. For equal micro-

grid thicknesses, homogeneity is better for large

apertures than for small ones. The grid thickness has

no influence. 300 µm apertures seem interesting for

two reasons. First, the apertures are small enough so

that the blood doesn't escape from the grid before the

latter is in contact with the cardboard blotter.

Secondly, such a dimension is compatible with the

industrial machining. The manufacture of such tips

will therefore be cost-effective.

5 CONCLUSIONS

In this paper, we have presented new medical

devices that reduce pain and should allow screening

a larger number of diseases in newborns. They are

meant to replace the technology currently used in

BIODEVICES 2009 - International Conference on Biomedical Electronics and Devices

294

neonatal blood sample screening. The origin of this

work is a study of the pain felt by the newborns.

This has highlighted that both, the sting and the

pressure required for the blood collection where

painful. We therefore studied a micro-needles array

as well as a system that suppresses pressures on the

children's heel. The ulterior motive of this work is to

improve neonatal blood sample screenings and

therefore to increase the number of screened

diseases and try to generalise this technique to a

places where it is not yet done.

ACKNOWLEDGEMENTS

This work is supported by the French Health

Ministry through a Hospital Protocol for Clinical

Research.

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Improving Blood Sample Quality

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