Microfluidics for Biologists Fundamentals and Applications

mouse multipotent progenitor cells, the cell-cell heterogeneity is found to be
connected with cell-fate decisions [ 51 , 52 ].
The analysis of single cells, however, presents a variety of challenges including
micrometer sizes of cells, presence of macromolecules of interest (mRNA and
proteins) in low copy numbers, etc. Therefore, there is an urgency for techniques
which can handle such small volumes without significant dilution and can be
directly integrated with ultrasensitive detection schemes [ 53 ]. Moreover, cells
must be treated gently before analysis so as not to perturb the biochemical pathways
or molecules of interest. Finally, although one wants to examine only one cell at a
time, many individual cells need to be analyzed rapidly to understand the statistical
distribution of a particular analyte in the cell population, so that the potential
disease biomarkers can be identified.
Analysis of single cell can be of two types: whole cell analysis and analysis of
cell lysates. The most critical step in both is the development of techniques that can
reproducibly transport cells to precise locations for further analysis [ 29 ]. Various
on-chip culture, immobilization methods, and cell trapping techniques were applied
for the purpose. Ideally, these methods should be amenable to parallel formats, have
high throughput capability, limit dilution, and be robust. The reported single-cell
manipulation techniques include: (a) hydrodynamic flow and focusing [ 54 ]; (b) use
of on-chip valves and pumps to direct cell transport [ 55 ]; (c) incorporation of cells
into MF droplets [ 56 ]; (d) optical and optoelectronic trapping of cells [ 57 ];
(e) dielectrophoretic trapping of cells [ 58 ], and; (f) geometrical trapping of cells
[ 59 – 61 ] (Fig.8.6A)[ 62 ]. The hydrodynamic focusing takes advantage of the fact
that the Reynolds number for fluid flow in MF devices is generally<0.1, so the fluid
flow is laminar [ 64 ]. Thus, through careful control of flow rates by multiple pumps

Table 8.1 Different organ on chip devices and their applications

Organ on chip MF Platform used Application References

Kidney, brain,

heart, lung and

liver

Physiologically-based

pharmacokinetic (PBPK)

model

ADME profiling and quantifi-

cation of the amount of drugs in

different parts of the body

[ 25 , 40 ]

Gastrointestinal

tract and liver

Microscale cell culture

analog (μCCA)

Evaluating nanoparticle toxicity

and interactions with tissues

[ 41 ]

Liver, tumor

and marrow

Pharmacokinetic-pharma-

codynamic (PK-PD) model

combined with aμCCA

Testing drug toxicity and

improve insights into the drug’s

mechanism of action

[ 25 ]

Gastrointestinal

tract and liver

Gut-parallel tube model Investigating paracetamol first

pass metabolism in intestine and

liver

[ 42 ]

Intestine, liver,

skin and Kidney

Four-Organ-Chip ADME profiling and toxicity

testing

[ 37 ]

Liver, colorectal

tissues

96-well format-based

microfluidic platform

Testing effects of different con-

centrations drug in several

tissues

[ 43 , 44 ]

Lung, gut PDMS-based organs-on-

chip

Prediction of clinical responses

in humans

[ 28 , 45 ]

8 Biological Applications of Microfluidics System 205