An Automated Medical Device for Ultimate ABO Compatibility Test

at the Patient’s Bedside

Towards the Automation of Point-of-care Transfusion Safety

Karine Charrière

, Alain Rouleau

, Olivier Gaiffe

, Pascal Morel

, Véronique Bourcier

Christian Pieralli

, Wilfrid Boireau

, Lionel Pazart

and Bruno Wacogne

1,2

INSERM CIC 1431, Besançon University Hospital, 25000 Besançon, France

FEMTO-ST Institute, UMR CNRS 6174, 15 B Avenue des Montboucons, 25030 Besançon cedex, France

Etablissement Français du Sang Bourgogne/Franche-Comté, 25000 Besançon, France

Hemovigilance Service, Besançon University Hospital, 25000 Besançon France

Keywords: Biosensor, Surface Plasmon Resonance, Human Red Blood Cells, Automated ABO Compatibility Test,

Optical Detection, Opto-Fluidic Prototype.

Abstract: In blood transfusion, accidents still occur because of ABO mismatch between donor and patient’s blood.

These errors, sometimes lethal, are principally due to wrong identification of patient and/or blood product or

to human errors. The best way to avoid these errors is to perform an ultimate ABO compatibility test at the

patient’s bedside immediately prior to transfusion. Ideally, this test should be performed automatically,

without human interpretation and with minimum blood exposure for nurses. This ideal and ultimate method

is not yet employed because of the lack of suitable device. In this paper, we propose a system that may fulfil

the above mentioned requirements. It is based on selective blood capture on biochip surfaces in a device

which automatically drives the different fluids, performs optical detection of captured red cells and finally

interprets the optical reading in terms of ABO compatibility. So far, our device achieved blood

compatibility test with 99.3 % sensitivity and 97.9 % specificity.

1 INTRODUCTION

In the field of blood transfusion, in all countries, a

concordance verification test is performed at the

patient’s bedside (concordance regarding the

patient’s identity and various elements that had

allowed the blood product delivery). In most

countries, a laboratory cross-match test is performed

before the concordance test. However, it becomes

useless when an error occurs after the delivery (the

wrong blood bag to the wrong patient, the most

frequent case). In very few countries (in France for

example), a second blood compatibility test is

performed at the patient’s bedside.

In countries where a unique test is performed at

the patient’s bedside and for which the hemo-

vigilance is reliable, the ratio of adverse effects due

to ABO incompatibility approaches 1/40000 red cell

concentrate (RCC). This was the case in France

before 2003 when only ABO compatibility was

tested. This is still the case in some countries where

only the concordance test is considered. After 2003

in France, the use of both concordance and ABO

tests at the patient’s bedside reduced the adverse

effects to about 1/600000 (in those very few cases,

concordance test had been omitted).

Based on these data, most countries are seeking a

second test at the patient's bedside in order to reduce

their number of ABO errors. However, the ABO test

cards used in France rely on delicate manual

operation and require a long and specific training.

Therefore, they appear difficult to be rapidly

employed worldwide. Furthermore, the

compatibility card still requires a human

interpretation of the agglutination test. Although iso-

group compatibility does not require difficult

interpretation of the agglutination test, non iso-group

compatibility is still subject to interpretation errors.

Indeed, the use of the current card is relatively

difficult and is the source of several errors as

illustrated later.

Charrière K., Rouleau A., Gaiffe O., Morel P., Bourcier V., Pieralli C., Boireau W., Pazart L. and Wacogne B..

An Automated Medical Device for Ultimate ABO Compatibility Test at the Patient’s Bedside - Towards the Automation of Point-of-care Transfusion Safety.

DOI: 10.5220/0005248700580067

In Proceedings of the International Conference on Biomedical Electronics and Devices (BIODEVICES-2015), pages 58-67

ISBN: 978-989-758-071-0

 2015 SCITEPRESS (Science and Technology Publications, Lda.)

All these facts highlight the need for a point-of-

care device able to automatically perform an

ultimate compatibility test with minimum

manipulation and without human interpretation. This

becomes urgent when considering the increase of

blood product distributed during the last decade. For

example in France an increase of the RCC delivery

of almost 24% has been observed between 2000 and

2011 (EFS, 2012). In 2011, more than 2.3 millions

of RCC where distributed (ANSM, 2012).

Several methods have been proposed for blood

typing. They are mainly based on gel agglutination

(Cid, 2006 – Langston, 1999). SPR (Malomgre,

2009 – Quinn, 2000 – Quinn, 1997) and Surface

Plasmon Resonance imaging (SPRi) (Berthier, 2011

– Boozer, 2006 – Campbell, 2007 – Mansuy-

Schlick, 2006) techniques can also be used.

However, these studies demonstrate the possibility

to detect captured cells with commercial laboratory

apparatuses. Therefore, a direct translation to the

patient’s bedside may be difficult because the entire

device used should be re-thought for point-of-care

use.

Recently, long-range surface plasmon-polaritons

to detect red blood cells (RBC) selectively captured

by the surface chemistry was demonstrated (Krupin,

2014). However, because packed RBC must be

diluted in a buffer of controlled refractive index,

translation of the device to clinical use is still

challenging.

Techniques based on image processing on plate

test have been reported (Ferraz, 2010 – Ferraz,

2013). In this case, image processing is used to

objectively observe and interpret red cell

agglutination obtained manually. Issues concerning

blood and antibodies manipulation still exist.

Spectroscopic methods have also been reported

(Ramasubramanian, 2008 and 2009). However, the

use of an optical spectrometer to measure absorption

of diluted red cells may be difficult in clinical

practice.

In fact, although these new devices are able to

realize blood typing by objectively reading

agglutination, they still require hard translational

research work before to be installed in the patient’s

room.

In this paper, we present a mobile device meant

to address the above mentioned issues. The main

idea is to replace the four reaction zones of the

manual compatibility card with four IgMs grafted

biochips (two for the patient and two for the RCC)

inspired from Surface Plasmon Resonance (SPR)

and SPRi biochips. Hemagglutination is therefore

replaced by red cell capture. The detection of

capture red cells does not rely on SPR anymore. A

simple optical absorption technique is used.

Biochips are inserted in a mobile reader/actuator that

drives the fluids (blood, RCC and physiological

serum) and performs the optical reading and final

interpretation.

Overall, research actions to set-up what we

named SmarTTransfuser include four main steps.

The first series of test consisted in studying the IgMs

grafting and red cell capture using SPR and SPRi

methods with homemade biochips. This has been

previously reported (Charrière, 2011 and 2012) and

will be briefly mentioned.

The second set of experiments consisted in

translating the SPR biochip to biochips inserted into

cartridges and to detect the capture of red cells in

these half-bulk conditions together with the

correlation between the number of captured cells and

optical reading (article in press).

The third part of the experiments is the subject of

the current publication. It consists in using a large

number of whole blood (WB) and RCC samples to

test the automated fluid flow control, optical reading

and software interpretation of the ABO

compatibility result. The goal is to determine

sensitivity and specificity of the device together with

the blood group concordance between what is

expected and what the device reads. We also studied

the performance of the device according to the age

of RCC.

The last part of the work will consist in inserting

the mobile device directly into the transfusion line

and to test the fluid flows and device compatibility

in a clinical-like situation before to envisage clinical

trials. This will be reported later.

In what follows, we present the general

SmarTTransfuser concept. We then briefly recall

biochips fabrication and testing using SPR and SPRi

techniques. In section 4, we will present the

SmarTTransfuser device before to present the

experimental studies and corresponding results.

Then, a conclusion and future work will be

proposed.

2 GENERAL CONCEPT

2.1 Current Card Test Technique and

Sources of Errors

Figure 1 shows the principle of current ABO

compatibility cards.

The principle consists in hydrating four reactive

zones. Two for the patient are coated with anti-A

AnAutomatedMedicalDeviceforUltimateABOCompatibilityTestatthePatient'sBedside-TowardstheAutomationof

Point-of-careTransfusionSafety

and anti-B IgMs, the same for the RCC. Blood is

sampled from the patient using a special needle. The

blood drop must be carefully deposited on the

patient's corresponding collection area. The same

holds for RCC aliquot. Once both bloods are

deposited in corresponding areas, the four antibody

zones must be hydrated using physiological serum.

Doing this, cross-contamination between antibodies

of different nature must be avoided.

One spatula is used to transfer the right quantity

of patient's blood to its corresponding anti-A zone.

The right blood volume must be taken at the first

attempt. A new spatula must be used for each of the

four blood transfers to avoid cross-contamination.

After this, the card is slightly shaken until a

possible hemagglutination is observed.

Figure 1: Current ABO compatibility cards.

Finally, the compatibility rules are applied to

interpret the results: for the same antibody zones,

positive reaction on RCC reaction zone and negative

on patient reaction zone forbids transfusion.

interpreting the card,

nurses decide if transfusion is

allowed or not. This method is the source of various

errors.

- Manipulation errors: cross contamination while

transferring bloods or hydrating antibodies.

- Reading errors: hemagglutination may be difficult

to observe, especially with patients requiring

transfusion.

- Interpretation errors.

- Risk of blood exposure when sampling patient's

blood.

Recently, cards a bit easier to use have been

proposed (ABTEST CARD®), but manipulation,

blood exposure and interpretation issues remains.

2.2 Concept of SmarTTransfuser

The general SmarTTransfuser concept is depicted in

figure 2. This concept is currently protected by two

patents (Pazart, 2011-1 and 2011-2).

As previously mentioned, two biochips are used to

test the patient’s blood. One is grafted with anti-A

IgMs the other one with anti-B IgMs. These two

biochips are inserted into a mobile cartridge.

Another similar cartridge is used to test the RCC.

The “patient” cartridge is connected to the patient’s

arm. Patient’s venous return is used to fill the

cartridge in order to minimise risks of blood

exposure. The “RCC” cartridge is connected to the

RCC.

Both cartridges are inserted into a mobile

reader/actuator. It is used to drive the fluids into the

cartridges (the measurement sequence will be

described later) and to perform the optical reading.

Embarked software is used to control ABO

compatibility. If bloods are compatible, the security

valve is opened and transfusion can be done.

Conversely, if bloods are not compatible, physicians

can either refuse the transfusion or force the security

valve to transfuse anyway (this may happen in

extreme cases).

Figure 2: General concept of SmarTTranfuser.

BIODEVICES2015-InternationalConferenceonBiomedicalElectronicsandDevices

3 BIOCHIP FABRICATION AND

TESTING

Here, we briefly recall the fabrication and testing of

biochips using SPR and SPRi techniques we

presented before (Charrière 2011 and 2012).

3.1 Chemical Functionalization and

SPR Experiments

Homemade chromium/gold biochips were

chemically functionalized as follows. The chemical

functionalization was obtained using a mixture of

11-mercapto-1-undecanol (11-MUOH) and 16-

mercapto-1-hexadecanoic acid (16-MHA)

(purchased from Sigma–Aldrich). The mixture of

11-MUOH/16-MHA (97/3 by mole) at 1mM in

absolute ethanol was sonicated for 10 min using an

Elma sonicator (power 90W, frequency 50/60 Hz).

Surfaces were rinsed by ethanol and ultra-pure water

and electrostatic preconcentration test was realized

with the Biacore™ 2000 apparatus at 25 °C at a rate

of 2 µL/min. Different immobilization pHs were

tested and the optimal pH conditions for promoting

functionalized antibody/surface interactions were

established. For each antibody, the best interaction

was obtained with pH 4.65.

Then, the carboxyl groups were activated using

240 µL of N-hydroxysuccinimide (NHS) at 10 mM

and 1-Ethyl-3-(3-dimethylaminopropyl) carbodi-

imide (EDC) at 48 mM (Amine Coupling Kit from

Biacore AB, Uppsala, Sweden) and incubated for 30

min at RT. Surfaces were rinsed by ultra-pure water.

This procedure prepares the chips for the

immobilization step.

The antibodies used were IgM anti-A or IgM

anti-B (DIAGAST, provided by the French Blood

Transfusion Center, Besançon). The running buffer

was saline phosphate buffer (PBS, 100 mM at

pH=7.4 with NaCl 50 mM). For each antibody, the

surface was nearly saturated after the first injection,

showing that our grafting conditions are optimized.

The grafting rate reaches 1500 IgMs/µm

average, which could potentially involve 100 000

antibodies for each captured red blood cell.

3.2 Red Cell Capture using SPR

Imaging

The biochip preparation was performed as described

above. Four spots of IgMs antibodies were grafted

onto the surface. Antibodies anti-A or anti-B were

diluted (1/10) in acetate buffer (0.1 mg/mL, pH=4.5)

and 2 spots of each specie (2 µL/spot) were

deposited on each surface and incubated for 1 hour

at room temperature in a humid chamber. Then a

blocking agent (Rat Serum Albumine 40 µg/mL,

pH=5.2) was used to passivate the surface by

incubation at room temperature for 30 min.

Incubation in ethanolamine (0.2 M) was then used to

target the free NHS entities in order to desactivate

the surface. Finally, the biochips were rinsed with

ultra pure water and used for SPRi experiments.

They were performed using a SPRi-Plex imager

(Horiba Scientific, France) equipped with a 660 nm

wavelength LED and a CCD camera.

Erythrocytes are captured according to the

compatibility rules: red cells from A group are

captured on the anti-A biochip only. B group red

cells are captured only on anti-B biochips. AB red

cells are captured on both anti-A and anti-B biochips

while O red cells are not captured at all.

Figure 3 shows SPRi images obtained with this

technique. This illustrates the ability of the biochips

to efficiently and selectively capture red blood cells

Figure 3: Selective capture of RBC using SPR imaging.

4 DESCRIPTION OF THE

DEVICE

Schematic views of the device are shown in figure 4.

Figure 4: Views of the device.

AnAutomatedMedicalDeviceforUltimateABOCompatibilityTestatthePatient'sBedside-TowardstheAutomationof

Point-of-careTransfusionSafety

The heart of the device consists of two

cartridges, one used to test the patient's blood, the

other for the RCC. Both of them contain two IgMs

grafted biochips, one with anti-A, the other with

anti-B antibodies. When blood (either WB or RCC)

is applied to the biochips, antigen-antibody

recognition occurs.

These microfluidic cartridges are placed into an

optical clamp that consists of blue LEDs and

photodetectors. Each biochip can then be

interrogated with its own LED/Detector pair. Red

cells trapped onto the biochip absorb light. The

detection principle consists in measuring the

transmission before red cells are driven onto the

chip, when physiological serum fills the circuitry,

(reference measurement) and after red cell/surface

interaction followed by washing with physiological

serum (final measurement). This is illustrated in

figure 5. The optical reading is therefore an

absorbance measurement given by:

absorbance = (reference-final)/reference (1)

Figure 5: Optical detection principle.

In what follows, positive chips are defined as

chips that have captured red cells, regardless of the

blood group. Conversely, negative chips correspond

to chip where no capture occurred.

Fluids (blood, RCC and physiological serum) are

driven by means of automated syringes controlled

via dedicated software. This software also drives the

optical measurement, human-machine interface and

USB connection to a PC for data recording and

processing.

Figure 6 shows an example of signal recording

corresponding to both positive (red curve) and

negative (blue curve) chips.

Figure 6: Example of recorded signal.

5 EXPERIMENTAL TESTING

The device was tested using 148 blood aliquots. This

represents 296 biochips and therefore 148 cartridges.

Blood comes from both RCC and WB. Samples

were provided by the French Blood Agency in

accordance with the ethic rules and with informed

consent obtained from donors.

Among these 296 chips, 4 are not taken into

account because errors occurred while assembling

the cartridges. The goal of this paper is to present de

behaviour of the device and not the ability to

correctly fabricate cartridges. Perfect fabrication of

cartridges will be the responsibility of the company

who eventually will fabricate the device according to

their own quality control policy.

Therefore, only 292 biochips were tested.

Remember that 2 biochips are required to test 1

sample. For two samples, inversions of the anti-A

and anti-B biochips were made. Although the

biochips behave correctly and are taken into account

for biochip testing, the corresponding samples were

not taken into account for compatibility testing. At

the end, 142 samples were tested for compatibility.

The repartition of samples in terms of RCC, WB

and blood group is given in table 1.

200

400

600

800

1000

1200

1400

1600

00:00 01:12 02:24 03:36 04:48 06:00 07:12 08:24

tage

(

Time

(

min

)

NaCl 0.9 % NaCl 0.9 %Blood

Negative

biochip

Positive

biochip

BIODEVICES2015-InternationalConferenceonBiomedicalElectronicsandDevices

Table 1: Number of samples used in this study.

Group A B AB O

RCC 19 25 14 20

17 13 20 14

In what follows, we present results concerning the

ability of the biochip to correctly capture red blood

cells regardless of the age of the blood, the

correlation between the red cell density on the chip

and the optical reading, the ability of the software to

interpret the result obtained from the optical reading

and the correlation between the tested blood group

and the blood group detected by the device.

5.1 Biochip Efficiency

Here, 292 biochips were tested. Figure 7 shows the

absorbance measured as a function of positive and

negative biochips for both RCC and WB. Positive

and negative biochips correspond to the 4 blood

group.

Figure 7: Absorbance versus positive or negative biochips.

Mean ± SD. Kruskal-Wallis test followed by Dunn’s

multiple comparison tests. *** p < 0.001. Negative values

are due to a slight drift of the electronics (also visible in

figure 9).

There is a strong difference between positive and

negative biochips. No statistical variation of the

absorbance was observed in negative biochips

(0.003 ± 0.001 for RCC neg and 0.007 ± 0.02 for

WB neg). Conversely, significant difference is

observed in positive biochips (0.36 ± 0.006 for RCC

pos and 0.18 ± 0.008 for WB pos). This result may

be related to the large difference of erythrocytes

number in samples (4.3x10

± 10

RBC/mL for RCC

and 10

C/mL for WB).

The best absorbance threshold to discriminate

between positive and negative biochip was set to

0.05 (minimization of mis-assignments). In this way,

only 4 errors occurred (red circles in the figure). One

biochip represents a false negative. For it, not

enough red cells were captured although the biochip

should have been positive. Indeed, red cell capture is

not homogenous on the surface, probably due to an

antibodies graft problem. This means that 1 patient

of group O was detected as A. Three other biochips

were false positive. For them a strong non-specific

retention of red cells was recorded due to washing

problem. This means that 1 patient of group O was

detected as A, 2 patients B detected as AB and 1

patient AB detected as A.

As seen in figure 8, this positive and negative

determination is obtained for A and B groups for

both RCC (0.38 ± 0.008 for RCC group A anti-A

and 0.0035 ± 0.003 for RCC group A anti-B; 0.003

± 0.004 for RCC group B ant-A and 0.35 ± 0.008 for

RCC group B anti-B) and WB (0.16 ± 0.014 for WB

group A anti-A and 0.001 ± 0.002 for WB anti-B;

0.024 ± 0.013 for WB group B anti-A and 0.17 ±

0.018 for WB group B anti-B). As expected, no

difference is observed between anti-A and anti-B

biochips for AB and O groups for both WB and

RCC. ).

Results given in figures 7 and 8 are in good

agreement with measurements made during the

second set of experiments described in the

introduction.

Figure 8: Absorbance versus blood group. . It shows the

absorbance as a function of the blood groups for both RCC

and whole blood. For each kind of sample, absorbance of

both anti-A and anti-B biochips are given. Mean ± SD.

Kruskal-Wallis test followed by Dunn’s multiple

comparison tests. *** p < 0.001.

AnAutomatedMedicalDeviceforUltimateABOCompatibilityTestatthePatient'sBedside-TowardstheAutomationof

Point-of-careTransfusionSafety

From these results, sensitivity and specificity of

the device can be calculated. For this, we consider

the following definitions.

- True positive chip (TP): red cells are present on

biochips when it should

- False positive chip (FP): red cells are present on

biochips when it should not.

- A true negative chip (TN) does not capture cells

when it should not.

- A false negative chip (FN) does not capture

cells when it should.

Now, sensitivity is defined as the probability to

record a positive test with positive biochips. It is

given by:

sensitivity = TP / (TP+FN) (2)

In the same manner, the specificity is defined as

the probability to record a negative test with

negative biochips. It is given by:

specificity = TN / (TN+FP) (3)

Table 2 presents the sensitivity and specificity of

biochips in terms of grafted antibodies for both RCC

and WB. Almost all sensitivities are 100%, except

for anti-B biochips (97%) used with WB (false

negative described earlier). It is the same for

specificities: all biochips are 100% specific, except

the anti-A biochips used with WB (3 false positives

described previously).

Table 2: System performance in terms of biochips.

RCC WB

Anti-A Anti-B Anti-A Anti-B

Number of

Biochips

82 78 68 64

Expected

positives

36 39 39 33

Recorded

positives

36 39 39 32

Sensitivity 100% 100% 100% 97%

Expected

negatives

46 39 29 31

Recorded

negatives

46 39 26 31

Specificity 100% 100% 89.7% 100%

Table 3 presents the same parameters regardless

of the blood type and for the entire device. At the

end, specificity of the device is 99.3% and

specificity is 97.9%. Improving fabrication of the

cartridges would probably resolve these mis-

assignments and improved sensitivity and

specificity.

Table 3: Performance in terms of antibodies and for the

entire device.

RCC + WB

Entire device

Anti-A Anti-B

Number of

Biochips

150 146 292

Expected

positives

75 72 147

Recorded

positives

75 71 146

Sensitivity 100% 98.6% 99.3%

Expected

negatives

75 70 145

Recorded

negatives

72 70 142

Specificity 96% 100% 97.9%

Biochips performance was also tested as a

function of the age of the blood donation. In this

case, only RCC were considered because WB is

meant to be fresh. For this test we used:

- 30 positive biochips with 6 to 8 days old

donations.

- 31 negative biochips with 6 to 8 days old.

- 29 positive with 43 to 44 days old.

- 40 negative with 43 to 44 days old.

Figure 9: Efficiency versus age in terms of

positive/negative.

Figure 9 shows the absorbance obtained in terms

of positivity/negativity while figure 10 refers to

blood groups. No difference was observed between

all kinds of positive biochips: 0.35 ± 0.011 for 6 to 8

days old RCC and 0.37 ± 0.01 for 43 to 4 days old

RCC. The same is observed between negative

biochips: 0.001 ± 0.002 for 6 to 8 days old RCC and

0.005 ± 0.002 for 43 to 44 days old RCC. Statistical

BIODEVICES2015-InternationalConferenceonBiomedicalElectronicsandDevices

Figure 10: Efficiency versus age in terms of blood groups.

analysis: Kruskal-Wallis test followed by Dunn’s

multiple comparison test.

It is quite clear that the age of the blood donation

does not impact biochips performances.

5.2 Correlation Between Red Cell

Concentration and Optical Reading

After each test, cartridges are dismounted and

biochips are observed with a microscope. Pictures of

five random zones of the chips are taken and the

number of red cells in each zone is counted using

ImageJ software. Figure 11 shows pictures of red

cells trapped on the biochip surface for both positive

and negative biochips.

Figure 11: Pictures of red cells capture for both positive

and negative biochips.

The percentage of surface occupied by red cells

is then calculated by averaging measurements in all

zones. Figure 12 shows the correlation between the

percentage of red cells captured on the biochips and

the absorbance measured for both RCC and WB.

Again, results given in figure 12 are in good

agreement with measurements made during the

second set of experiments described in the

introduction.

Figure 12: Correlation between percentage of captured

cells and optical reading.

5.3 Compatibility Interpretation

For this, 74 compatibility tests were performed. In

all cases the software delivered the right

compatibility information, perfectly coherent with

what happened at the biochip surface.

Of course, we mentioned cases where mis-

assignments occurred. However, this part of the test

concerns the fact that the device delivers the right

information from the result of the optical

measurement.

For example, with sample SO11 (WB of group

O), a strong non-specific RCC retention has been

observed on the anti-A biochip, with an absorbance

of 0.06 corresponding to a percentage of red cells of

21% on the biochip surface. This "patient" was

considered A group. When testing the compatibility

with B group RCC, the device concluded that the

transfusion should not be allowed. Therefore the

optical reading and the interpretation software work

properly.

This highlights the fact that mis-assignments

principally come from biochips dysfunctions.

5.4 Concordance Tests

The last experiment concerned the ability of the

device to correctly identify blood groups. Among

142 concordance tests performed 4 mis-assignments

occurred. The concordance performance is therefore

97% as detailed in table 4.

AnAutomatedMedicalDeviceforUltimateABOCompatibilityTestatthePatient'sBedside-TowardstheAutomationof

Point-of-careTransfusionSafety

Table 4: Detail of the concordance test (m-a: mis-

assignment).

Group A B AB O

RCC

N° of tests

19 25 14 20

Concordance

100 100 100 100

N° of tests

17 13 20 14

Concordance

100

84.6

2 m-a

1 m-a

94.4

1 m-a

All groups

RCC

+ WB

N° of test

142

Concordance

4 m-a

Mis-assignments reported here correspond to those

already mentioned in section 5.1.

6 CONCLUSIONS

In this paper, we presented a new device able to

semi-automatically perform an ultimate ABO

compatibility test. It is based on biochips grafted

with anti-A and anti-B antibodies. They are inserted

into disposable cartridges and placed into a mobile

and re-usable reader/actuator. The latter includes

embarked software that drives and controls the fluid

flows, performs the optical detection of captured red

cells and interpret the result in terms of ABO

compatibility.

In the current study, 292 biochips were tested.

The device exhibits sensitivity and specificity equal

to 99.3% and 97.9% respectively. We still need to

fully understand why 4

mis-assignments occurred

during these tests. However, for the 3 false positives,

washing was imperfect, probably due to a slight

motor dysfunction. For false negative biochips,

IgMs were probably not optimally grafted which

may explain the non-uniform red cells capture.

Optical reading and software interpretation are not to

be blamed. However, just after these 4 false results

have been observed, the same samples used with

new biochip were re-tested. This time, everything

worked correctly and no

mis-assignment was

observed.

Future work will consist in inserting the device

in the transfusion line and to control that RCC and

patient's blood are correctly driven onto the

biochips. Previous experiments (not shown here)

already demonstrated the efficient use of patient's

venous return in order to sample patient's blood with

minimum blood exposure risks.

To conclude, we believe that the

SmarTTransfuser concept may help enhancing blood

transfusion safety, not only in countries where a

double ultimate test is already performed, but also in

countries where only one test is considered.

Furthermore, such a device is meant to drastically

reduce non-compatibility accidents in countries

where the whole transfusion process (blood

donation, conservation, delivery and transfusion) is

not yet fully satisfactory.

ACKNOWLEDGEMENTS

This work was supported by the French

RENATECH network, the Etablissement Français

du Sang (EFS), the INSERM, the DGOS, the CNRS,

OSEO, the University of Franche-Comté

(“innovative project maturation” program) and the

European Community through the FEDER Program.

This work is developed in the frame of the Biom'@x

transversal axis at FEMTO-ST.

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AnAutomatedMedicalDeviceforUltimateABOCompatibilityTestatthePatient'sBedside-TowardstheAutomationof

Point-of-careTransfusionSafety