channel, this is achieved by the balance of two forces: (1) shear-

gradient inertial lift force induced by the velocity gradient of the

fluid, and (2) wall-induced lift force originated from wall lubrica-

tion effect and an asymmetry in pressure distribution around the

particle adjacent to the wall [5]. The balance between these two

forces develops particle equilibrium positions in the channel,

depending

on

the

channel

cross-sectional

shape

and

the

corresponding cross-laterally wall-effect lift force. Figure 1a illus-

trates four equilibrium positions of particles with a particle size a,

for a microchannel with a square cross section. The net inertial lift

force is a power-law function of particle size (FL ~ aⁿ, n > 1). When

the particle size relative to the channel hydraulic diameter (a/DH)

is greater than 0.07, the inertial focusing of neutrally buoyant

particles can be guaranteed [6].

Inertial microfluidics is divided into four types according to

their geometries: straight channels, serpentine channels, contrac-

tion–expansion channels, and spiral channels [7]. Adding curvature

to the channel generates a secondary flow perpendicular to the

main flow due to the centrifugal force. The secondary drag force

scales linearly with particle size (FD ~ a) [8], where coupling it with

the net inertial lift force leads to particle size-based differentially

equilibriums (Fig. 1b). Among these structured channels, spiral

microfluidic channels with trapezoidal cross-sections have the high-

est throughput in a single unit, with simple settings and high

recovery rate. These features enable the spiral channels as potential

candidates for large-volume liquid processing through multiplex-

ing [9, 10]. It has been demonstrated for cell retention in perfusion

bioreactors [11], as well as microcarrier-based adherent cells har-

vesting and microcarrier-cell complex retention in a perfusion con-

dition [8, 12]. It was showed that the sorted cells express their

normal surface markers, maintained the spindle morphology with

uncompromised growth kinetics, differentiation potency and ther-

apeutic properties after being processed by these devices. Com-

pared to the traditional harvesting technologies, the membrane

technology, spiral inertial microfluidic devices possess low-cost

attributes due to ease of fabrication and maintenance. There is no

need for frequent replacement due to clogging, which reduces the

cost and the risk of contaminations. The throughput can be scaled

out significantly by paralleling the spiral channels, while the foot-

print of the whole setup remains relatively small.

Here, we presented the 3D printing technology-based method

for rapid and low-cost fabrication of spiral microfluidic devices

through (1) direct printing of the microchannels and (2) printing

the master mold for soft lithography-based channel fabrication. We

demonstrated that this method is capable of fabricating microflui-

dic devices within 24 h and subsequently separate adherent cells

from microcarriers under high-throughput and scalable manner.

We have achieved 77% cell recovery rate with 99% microcarriers

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