Abstract

Modeling, simulation, and thermal performance analysis of a thermocycler for the continuous-flow polymerase chain reaction (CF-PCR), with a phase changing material (PCM)-laden annealing flow path, is presented. The incessant threat of microorganisms such as viruses, bacteria, and fungi has fostered effective, quick, and miniature detection devices in order to curtail the wide-spreading of infections. Microfluidics-based CF-PCR systems are compact and ideal for faster response. The thermal cycling process involves a sequential exposure of a given liquid sample to various temperature conditions when it is taken through the continuous-flow path. As a result, a prescribed periodic change of temperature suitable for deoxyribonucleic acid (DNA) amplification is achieved. A rapid temperature reduction and maintenance of isothermal conditions to facilitate the annealing phase of CF-PCR process by a PCM-assisted cooling is envisaged in the present study. Unsteady, two-dimensional, incompressible fluid flow, and internal convection heat transfer in a microchannel annealing path with melting of tetracosane (C24H50) boundary has been simulated using semi-implicit method for pressure linked equations-consistent (SIMPLEC) algorithm based finite volume solver. Solver validation is carried out against the experimental data on internal convection heat transfer in a rectangular microchannel. A detailed numerical study has been performed to assess the spatiotemporal heat transfer characteristics of internal convection in the microfluidic path when the flow triggers the melting of encapsulated PCM. A minimum sample flowrate with PCM encapsulation of less than 600 μm is found to be ideal for achieving desired thermal performance. The present study evidences the swift temperature reduction and management of isothermal conditions congenial for the annealing process in the CF-PCR system for various sample flowrates and PCM masses. The study offers valuable design input for the development of a microfluidic thermocycler for CF-PCR applications.

References

1.
Mullis
,
K. B.
,
1994
, “
The Polymerase Chain Reaction (Nobel Lecture)
,”
Angew. Chem. Int. Ed. Eng.
,
33
(
12
), pp.
1209
1213
.
2.
Chan
,
K.
,
Wong
,
P. Y.
,
Yu
,
P.
,
Hardick
,
J.
,
Wong
,
K. Y.
,
Wilson
,
S. A.
,
Wu
,
T.
,
Hui
,
Z.
,
Gaydos
,
C.
, and
Wong
,
S. S.
,
2016
, “
A Rapid and Low-Cost PCR Thermal Cycler for Infectious Disease Diagnostics
,”
PLoS One
,
11
(
2
), p.
e0149150
.
3.
Li
,
Y.
,
Xing
,
D.
, and
Zhang
,
C.
,
2009
, “
Rapid Detection of Genetically Modified Organisms on a Continuous-Flow Polymerase Chain Reaction Microfluidics
,”
Anal. Biochem.
,
385
(
1
), pp.
42
49
.
4.
Li
,
S.
,
Fozdar
,
D. Y.
,
Ali
,
M. F.
,
Li
,
H.
,
Shao
,
D.
,
Vykoukal
,
D. M.
,
Vykoukal
,
J.
, et al
,
2006
, “
A Continuous-Flow Polymerase Chain Reaction Microchip With Regional Velocity Control
,”
J. Microelectromech. Syst.
,
15
(
1
), pp.
223
236
.
5.
Lounsbury
,
J. A.
,
Karlsson
,
A.
,
Miranian
,
D. C.
,
Cronk
,
S. M.
,
Nelson
,
D. A.
,
Li
,
J.
,
Haverstick
,
D. M.
,
Kinnon
,
P.
,
Saul
,
D. J.
, and
Landers
,
J. P.
,
2013
, “
From Sample to PCR Product in Under 45 min: A Polymeric Integrated Microdevice for Clinical and Forensic DNA Analysis
,”
Lab Chip
,
13
(
7
), pp.
1384
1393
.
6.
Yang
,
J.
,
Liu
,
Y.
,
Rauch
,
C. B.
,
Stevens
,
R. L.
,
Liu
,
R. H.
,
Lenigk
,
R.
, and
Grodzinski
,
P.
,
2002
, “
High Sensitivity PCR Assay in Plastic Micro Reactors
,”
Lab Chip
,
2
(
4
), pp.
179
187
.
7.
Mohon
,
A. N.
,
Lee
,
L. D. Y.
,
Bayih
,
A. G.
,
Folefoc
,
A.
,
Guelig
,
D.
,
Burton
,
R. A.
,
LaBarre
,
P.
,
Chan
,
W.
,
Meatherall
,
B.
, and
Pillai
,
D. R.
,
2016
, “
NINA-LAMP Compared to Microscopy, RDT, and Nested PCR for the Detection of Imported Malaria
,”
Diagn. Microbiol. Infect. Dis.
,
85
(
2
), pp.
149
153
.
8.
Kumar
,
N.
, and
Banerjee
,
D.
,
2019
, “
Thermal Cycling of Calcium Chloride Hexahydrate With Strontium Chloride as a Phase Change Material for Latent Heat Thermal Energy Storage Applications in a Nondifferential Scanning Calorimeter Set-Up
,”
ASME J. Therm. Sci. Eng. Appl.
,
11
(
5
), p.
051014
.
9.
Quan
,
P. L.
,
Sauzade
,
M.
, and
Brouzes
,
E.
,
2018
, “
dPCR: A Technology Review
,”
Sensors
,
18
(
4
), p.
1271
.
10.
Wong
,
G.
,
Wong
,
I.
,
Chan
,
K.
,
Hsieh
,
Y.
, and
Wong
,
S.
,
2015
, “
A Rapid and Low-Cost PCR Thermal Cycler for Low Resource Settings
,”
PLoS One
,
10
(
7
), p.
e0131701
.
11.
Ririe
,
K. M.
,
Rasmussen
,
R. P.
, and
Wittwer
,
C. T.
,
1997
, “
Product Differentiation by Analysis of DNA Melting Curves During the Polymerase Chain Reaction
,”
Anal. Biochem.
,
245
(
2
), pp.
154
160
.
12.
Hecker
,
K. H.
, and
Roux
,
K. H.
,
1996
, “
High and Low Annealing Temperatures Increase Both Specificity and Yield in Touchdown and Stepdown PCR
,”
BioTechniques
,
20
(
3
), pp.
478
485
.
13.
Zhang
,
C.
,
Xu
,
J.
,
Ma
,
W.
, and
Zheng
,
W.
,
2006
, “
, “PCR Microfluidic Devices for DNA Amplification
,”
Biotechnol. Adv.
,
24
(
3
), pp.
243
284
.
14.
Park
,
N.
,
Kim
,
S.
, and
Hahn
,
J. H.
,
2003
, “
Cylindrical Compact Thermal-Cycling Device for Continuous-Flow Polymerase Chain Reaction
,”
Anal. Chem.
,
75
(
21
), pp.
6029
6033
.
15.
Zhang
,
Y.
, and
Ozdemir
,
P.
,
2009
, “
Microfluidic DNA Amplification—A Review
,”
Anal. Chim. Acta
,
638
(
2
), pp.
115
125
.
16.
Jaguemont
,
J.
,
Omar
,
N.
,
Van den Bossche
,
P.
, and
Mierlo
,
J.
,
2018
, “
Phase-Change Materials (PCM) for Automotive Applications: A Review
,”
Appl. Therm. Eng.
,
132
, pp.
308
320
.
17.
Hua
,
W.
,
Zhang
,
L.
, and
Zhang
,
X.
,
2021
, “
Research on Passive Cooling of Electronic Chips Based on PCM: A Review
,”
J. Mol. Liq.
,
340
, p.
117183
.
18.
Li
,
W. Q.
,
Wan
,
H.
,
Jing
,
T. T.
,
Li
,
Y. B.
,
Liu
,
P. J.
,
He
,
G. Q.
, and
Qin
,
F.
,
2019
, “
Microencapsulated Phase Change Material (MEPCM) Saturated in Metal Foam as an Efficient Hybrid PCM for Passive Thermal Management: A Numerical and Experimental Study
,”
Appl. Therm. Eng.
,
146
, pp.
413
421
.
19.
Guo
,
Y.
,
Ma
,
H.
,
Fu
,
B.
,
Ji
,
Y.
,
Su
,
F.
, and
Wilson
,
C.
,
2019
, “
Heat Transfer Analysis of Flash Evaporation With MEPCM
,”
ASME J. Therm. Sci. Eng. Appl.
,
11
(
5
), p.
051016
.
20.
Indulakshmi
,
B.
, and
Madhu
,
G.
,
2018
, “
Effect of Phase-Changing Material Encapsulation on Flow Boiling in a Microchannel-Based Electronics Cooling System
,”
Multiph. Sci. Technol.
,
30
(
2–3
), pp.
221
237
.
21.
Abed
,
W. M.
,
Whalley
,
R. D.
,
Dennis
,
D. J.
, and
Poole
,
R. J.
,
2016
, “
Experimental Investigation of the Impact of Elastic Turbulence on Heat Transfer in a Serpentine Channel
,”
J. Non-Newtonian Fluid Mech.
,
231
, pp.
68
78
.
22.
Talebizadehsardari
,
P.
,
Mohammed
,
H. I.
,
Mahdi
,
J. M.
,
Gillott
,
M.
,
Walker
,
G. S.
,
Grant
,
D.
, and
Giddings
,
D.
,
2021
, “
Effect of Airflow Channel Arrangement on the Discharge of a Composite Metal Foam-Phase Change Material Heat Exchanger
,”
Int. J. Energy Res.
,
45
(
2
), pp.
2593
2609
.
23.
Ho
,
C. J.
,
Guo
,
Y.-W.
,
Yang
,
T.-F.
,
Rashidi
,
S.
, and
Yan
,
W.-M.
,
2020
, “
Numerical Study on Forced Convection of Water-Based Suspensions of Nanoencapsulated PCM Particles/Al2O3 Nanoparticles in a Mini-Channel Heat Sink
,”
Int. J. Heat Mass Transfer
,
157
, p.
119965
.
24.
Li
,
Z.
,
Li
,
Y.
,
Sekine
,
S.
,
Xi
,
H.
,
Amano
,
A.
,
Zhang
,
D.
, and
Yamaguchi
,
Y.
,
2020
, “
Design and Fabrication of Portable Continuous Flow PCR Microfluidic Chip for DNA Replication
,”
Biomed. Microdevices
,
22
(
1
), pp.
1
7
.
25.
Kulkarni
,
M. B.
,
Goyal
,
S.
,
Dhar
,
A.
,
Sriram
,
D.
, and
Goel
,
S.
,
2021
, “
Miniaturized and IoT Enabled Continuous-Flow-Based Microfluidic PCR Device for DNA Amplification
,”
IEEE Trans. NanoBiosci.
,
21
(
1
), pp.
97
104
.
26.
Bondareva
,
N. S.
, and
Sheremet
,
M. A.
,
2018
, “
Conjugate Heat Transfer in the PCM-Based Heat Storage System With Finned Copper Profile: Application in Electronics Cooling
,”
Int. J. Heat Mass Transfer
,
124
, pp.
1275
1284
.
27.
Arshad
,
A.
,
Jabbal
,
M.
,
Sardari
,
P. T.
,
Bashir
,
M. A.
,
Faraji
,
H.
, and
Yan
,
Y.
,
2020
, “
Transient Simulation of Finned Heat Sinks Embedded With PCM for Electronics Cooling
,”
Ther. Sci. Eng. Prog.
,
18
, p.
100520
.
28.
Kalidasan
,
B.
,
Pandey
,
A. K.
,
Shahabuddin
,
S.
,
Samykano
,
M.
,
Thirugnanasambandam
,
M.
, and
Saidur
,
R.
,
2020
, “
Phase Change Materials Integrated Solar Thermal Energy Systems: Global Trends and Current Practices in Experimental Approaches
,”
J. Energy Storage
,
27
, p.
101118
.
29.
Osterman
,
E.
,
Tyagi
,
V. V.
,
Butala
,
V.
,
Rahim
,
N. A.
, and
Stritih
,
U.
,
2012
, “
Review of PCM Based Cooling Technologies for Buildings
,”
Energy Build.
,
49
, pp.
37
49
.
30.
Indulakshmi
,
B.
,
Prasad
,
N.
, and
Kumar
,
R. S.
,
2022
, “
Passive Control of Annealing in Polymerase Chain Reaction Using Phase Changing Materials
,”
IEEE International Conference on Signal Processing, Informatics, Communication and Energy Systems (SPICES)
(Vol.
1
, pp.
158
161
).
IEEE
.
31.
Qiu
,
X.
,
Zhang
,
S.
,
Xiang
,
F.
,
Wu
,
D.
,
Guo
,
M.
,
Ge
,
S.
,
Li
,
K.
,
Ye
,
X.
,
Xia
,
N.
, and
Qian
,
S.
,
2017
, “
Instrument-Free Point-of-Care Molecular Diagnosis of H1N1 Based on Microfluidic Convective PCR
,”
Sens. Actuators, B
,
243
, pp.
738
744
.
32.
Buser
,
J. R.
,
Diesburg
,
S.
,
Singleton
,
J.
,
Guelig
,
D.
,
Bishop
,
J. D.
,
Zentner
,
C.
,
Burton
,
R.
,
LaBarre
,
P.
,
Yager
,
P.
, and
Weigl
,
B. H.
,
2015
, “
Precision Chemical Heating for Diagnostic Devices
,”
Lab Chip
,
15
(
23
), pp.
4423
4432
.
33.
Weigl
,
B.
,
Domingo
,
G.
,
LaBarre
,
P.
, and
Gerlach
,
J.
,
2008
, “
Towards Non-and Minimally Instrumented, Microfluidics-Based Diagnostic Devices
,”
Lab Chip
,
8
(
12
), pp.
1999
2014
.
34.
Madruga
,
S.
,
Haruki
,
N.
, and
Horibe
,
A.
,
2018
, “
Experimental and Numerical Study of Melting of the Phase Change Material Tetracosane
,”
Int. Commun. Heat Mass Transfer
,
98
, pp.
163
170
.
35.
Voller
,
V. R.
, and
Swaminathan
,
C. R.
,
1991
, “
ERAL Source-Based Method for Solidification Phase Change
,”
Numer. Heat Transf. A, Part B Fundam.
,
19
(
2
), pp.
175
189
.
36.
Akula
,
R.
, and
Balaji
,
C.
,
2021
, “
Thermal Performance of a Phase Change Material-Based Heat Sink Subject to Constant and Power Surge Heat Loads: A Numerical Study
,”
ASME J. Therm. Sci. Eng. Appl.
,
13
(
3
), p.
031014
.
37.
ANSYS Fluent
,
2011
,
Fluent 14.0 User’s Guide
,
Ansys Fluent Inc
., Canonsburg, PA.
38.
Steinke
,
M. E.
,
Kandlikar
,
S. G.
,
Magerlein
,
J. H.
,
Colgan
,
E.
, and
Raisanen
,
A. D.
,
2005
, “
Development of an Experimental Facility for Investigating Single-Phase Liquid Flow in Microchannels
,”
International Conference on Nanochannels, Microchannels, and Minichannels
,
Toronto, Canada
,
June 13–15
, Vol.
41855
, pp.
233
243
.
You do not currently have access to this content.