Table 3.

Recent approaches for integrating adipose tissue or pre-differentiated cells onto microfluidic devices for dynamic functional studies

Entry	Cell type	Microfluidic device details	Cell trapping mechanism	Analytical method(s)	Temporal resolution	Notes	Year	Ref.
1	3T3-L1 adipocytes	etched glass substrate, reversibly sealed 2-layer design	cover slip with differentiated cells sealed into on-chip chamber	fluorescence on-chip; coupled enzyme assay for glycerol	1.5 min	First example of temporally-resolved, microfluidic sampling of adipocytes; on-chip, continuous flow enzyme assays quantified glycerol secretion.	2009	[46]
2	3T3-L1 adipocytes	etched glass substrate and PTFE sheet, reversibly sealed 3-layer design	cover slip with differentiated cells sealed into on-chip chamber	fluorescence on-chip; coupled enzyme assay for NEFA	1.4 min	First example of temporally-resolved, microfluidic sampling of NEFA secretion from adipocytes.	2010	[47]
3	3T3-L1 adipocytes (spheroids)	PDMS substrate	trapped in collagen gel (20 μL) in microdevice outlet reservoir	fluorescence off-chip; coupled enzyme assay for glucose	25 min(single treatment)	First microfluidic system evaluating insulin-dependent glucose uptake in adipocytes; first study on the impor- tance of tissue scaling in organs-on--a-chip.	2013	[41]
4	3T3-L1 adipocytes	PDMS substrate, reversibly sealed 3-layer design, on-chip valves	cover slip with differentiated cells sealed into on-chip chamber	fluorescence on-chip; coupled enzyme assays for both NEFA and glycerol	2.3 min	First example of multiplexed assays for quantifying lipolysis products secreted by adipocytes on-chip; first example of on-chip valving for adipocyte perfusion.	2014	[48]
5	primary mouse adipocytes (dispersed)	PDMS substrate, customized primary tissue culture reservoir	collagen	ELISA	60 min(single treatment)	First example of adipokine secretion by adipocytes on microfluidic devices.	2015	[45]
6	primary human adipose tissue (explants)	PDMS substrate, on-chip valves	capped tissue culture chamber above a micropost array	glucose meter	~2 min(not explicitly stated)	First comparison of adipose tissue glucose uptake by diabetic and nondiabetic human adipose tissue.	2015	[52]
7	primary mouse adipose tissue (explants)	PDMS substrate, custom 3D printer templated culture reservoir	3D-printed explant trap accessory	fluorescence off-chip; coupled enzyme assay for glycerol	10 min	First example of temporally-resolved microfluidic sampling of primary murine WAT explants; first report of 3D printer templated culture reser- voir and explant traps.	2016	[44]
8	primary brown adipocytes	etched glass and silicon substrates, on-chip silicon resonators	single cells trapped in microchannels	silicon resonator based thermal measurement	real-time(sub-second capable)	First example of microfluidic interrogation of brown adipocytes; first measurement of heat generation from single adipocytes.	2016	[51]
9	3T3-L1 adipocytes	PDMS substrate, reversibly sealed 3-layer design, on-chip valves	cover slip with differentiated cells sealed into on-chip chamber	solid-phase extraction, mass spectrometry (SPE-MS)	30 min	First integration of microfluidics and mass spectrometry for detection of NEFA profile secreted by adipocytes.	2017	[49]
10	primary mouse adipose tissue (explants)	PDMS substrate, on-chip valves, custom 3D printer templated culture reservoir	platinum mesh explant trap	fluorescence imaging of adipocytes on-chip	real-time(sub-second capable)	First observation of real-time free fatty acid exchange as a function of dy- namic glucose and insulin inputs	2017	[39]