Figure 1. Air-liquid Cavity Acoustic Transducers
(ALCATs). The air is trapped within side
channels. The interface between the air and liquid
will vibrate when ultrasound is applied causing
streaming patterns indicated by the arrows. The
net flow of liquid is in the direction of the black
arrows. The swirling red arrows represent eddies
where erythrocytes are predominantly trapped.
RAPID BLOOD PLASMA SEPARATION WITH AIR-LIQUID CAVITY
ACOUSTIC TRANSDUCERS
Arlene Doria*
1
, Maulik Patel
1
, and Abraham P. Lee
1
1
Department of Biomedical Engineering, University of California - Irvine, USA
biomint.eng.uci.edu
ABSTRACT
Herein we present a fast and low cost separation strategy that utilizes air-liquid cavity acoustic transducers (ALCATs) to
extract plasma from human whole blood. ALCATs are oscillating air-liquid interfaces that are acoustically driven and
produce microstreaming within liquids in microfluidic channels. With whole blood, the streaming patterns induced by
ALCATs include swirling eddies where erythrocytes become aggregated. The device is designed to have a dense array of
ALCATs that simultaneously serve to pump fluid forward and to trap red blood cells. Due to the trapping effect, red blood
cells have a longer path to be propelled downstream while plasma continues flowing forward resulting in a rapid extraction of
plasma. With microsample volumes in one device, 40% of plasma was yielded from a 16 μL sample of EDTA spiked whole
blood within minutes of activating the acoustic source. The plasma volumes and plasma extraction rates can be of practical
use in many point-of-care applications.
KEYWORDS: point of care, blood plasma separation, sample preparation, air-liquid cavity acoustic transducers, whole
blood, red blood cells, erythrocytes, point of care diagnostics
INTRODUCTION
A fast and low cost on-chip sample preparation method is a critical component for effective point-of-care (POC)
diagnostics [1]. The rapid extraction of plasma from whole blood is an important sample prep method to prevent blood
components from interfering with assay analyses downstream. Specifically, aggregation of erythrocytes in a chip’s optical
detection zone can precipitously degrade signal quality. In the absence of a blood-plasma separation method, extra wash
steps are required, thus, increasing sample-to-answer times. A lot of effort has been devoted to the separation of components
from blood in various microfluidic systems. Separation strategies include the use of mechanical forces (e.g. centrifugation,
filtration, sedimentation, and the Zweifach–Fung effect), magnetic interactions, optical interactions, and dielectrophoresis [2]
[3]. However, many of these strategies have practical limitations in cost, time, and scale up. For example, centrifugation and
sedimentation methods can be time-consuming. Many commercial
filtration methods in POC utilize glass fiber or membrane filters that
require complex and costly processing of filters with multiple
reagents in order to reduce non-specific binding of the analyte of
interest or to reduce hemolysis effects. Furthermore, most methods
have limited control of the quantity of plasma that can be extracted.
Many microfluidic separation methods also require diluted blood
samples. Hence, there is increasing demand for better plasma
separation strategies from whole blood.
THEORY
When liquid fills the main microchannels of hydrophobic
devices, pockets of air are trapped within dead-end side channels.
Applying an acoustic source will cause the interfaces between air
and liquid to oscillate, thereby, creating microstreaming patterns
within a localized region of the surrounding liquid (Figure 1). These
air liquid cavity acoustic transducers (ALCATs) have been shown to
be useful for pumping, mixing, and bead trapping [4]. When whole
blood is pumped through an array of activated ALCATs, the red
blood cells will agglomerate within streaming eddies. These eddies
978-0-9798064-4-5/μTAS 2011/$20©11CBMS-0001 1882
15th International Conference on
Miniaturized Systems for Chemistry and Life Sciences
October 2-6, 2011, Seattle, Washington, USA