WHOLE BLOOD PLASMAPHERESIS USING ACOUSTIC SEPARATION CHIPS

Author ： Andreas Nilsson, Filip Petersson and Thomas Laurell Dept. of Electrical Measurements, Lund University, P.O. Box 118, S-221 00 Lund, SWEDEN

Reporter: Wun-Hao Wu (Wun-Hao Wu ( 吳文豪吳文豪 )) 12/26, 2007

Outline

Introduce Theory Fabrication Result References

IntroduceThe need for pure blood plasma is of interest in diagnostic applications and in blood banking e.g. plasmapheresis. Blood plasma is usually generated by centrifugation or filtration. Plasmapheresis as realized by centrifugation in blood bank processes has hitherto not been addressed by μTAS solutions as throughput is a major issue. This paper describes a method of extracting pure blood plasma from whole blood based on previously reported ultrasonic standing wave separation technique , offering a potential of up-scaling throughput to clinically relevant levels.

Figure A single plasmapheresis chipactuated by a piezoceramic from thebackside.

Theory

An acoustic standing wave is commonly described according to eqn. (1).

(1)

If the acoustic field is in the form of a standing wave, eqn. (1) can be rewritten in terms of pressure eqn. (2).

p = p0 ·sin(kx)· cos(wt)

According to the acoustic force theory presented by Yosioka and Kawasima the force on a particle can be expressed in the following way eqn.(3).

Vc is the volume of the particle, p0 is the pressure amplitude from

eqn. (2) and φ is defined by eqn. (4). The density of the

medium and particles are denoted ρw and ρc respectively and

the corresponding compressibilities βw and βc.

(2)

(3)

(4)

Theory

Φ < 0 ex. lipid particles Φ -0.3≦

Φ >0 ex. Erythrocytes Φ 0.3≧

Fabrication

Si

UV

PR

Si

PR

Si

PRKOH1.

2.

3.

Si

Glass bonding

4.

示意圖

Result

Fig. Particle enrichment in the micro channel. The bands show the enriched particles in resonance mode, 1st, 2nd and 3rd harmonic with 2, 3 and 4 bands respectively, A) top view microscope photographs and B) principalseparation channel cross-sections. Channel

width: 750 μm, channel depth:250 μm.

Fig. a. Cross-type structure with a two band formation. b. 45°-structure with a two band formation.

Received 24th October 2003, Accepted 11th December 2003First published as an Advance Article on the web 9th February 2004

Result

Fig. 8 (a) Milk flowing through the 350μm separation chip with ultrasound turned off. (b)

Milk flowing through the 350 μm separation chip with ultrasound turned on. (c) A mixture

of milk and blood flowing through the 350 μm separation chip with ultrasound turned on.

Fig. 11 Lipid particles separated from erythrocytes at the

trifurcation of 350 μm separation chip with ultrasound turned on.

Received 16th April 2004, Accepted 21st June 2004First published as an Advance Article on the web 18th August 2004

Result

Figure . The eight channel separator. The topview to the right shows a channel segment withultrasound turned off. The lower right viewshows the acoustically controlled plasmaextraction. White lines have been added tooutline the separator channels.

Figure . Sequential plasma extraction fromwhole blood. The plasma fraction from the firststep is the input to the second step and so on.

Result

Figure . The diagram shows the removal efficiency of erythrocytes vs hematocrit (HCT) level. The HCT after each extraction step is followed by the step function. The process starts with whole blood of 40 % and end up with a plasma fraction containing less than 1 % erythrocytes.

References

1. Nilsson, A., et al., Acoustic control of suspended particles in micro fluidic chips.

Lab on a Chip, 2004. 4(2): p. 131-135.2. Petersson, F., et al., Separation of lipids from blood utilizing ultrasonic standing waves in microfluidic channels. Analyst, 2004. 129(10): p. 938-943.3. Jonsson, H., et al., Particle Separation Using Ultrasound Can Radically Reduce Embolic Load to Brain After Cardiac Surgery. The Annals of Thoracic Surgery,

2004.78(5): p. 1572-15774. K. Yosioka and Y. Kawasima, Acoustic radiation pressure on a compressible sphere, Acustica, 1955, 5, 167–173.