Analytical and Bioanalytical Chemistry

, Volume 411, Issue 20, pp 5297–5307 | Cite as

Ultrafast, low-power, PCB manufacturable, continuous-flow microdevice for DNA amplification

  • Georgia D. Kaprou
  • Vasileios Papadopoulos
  • Dimitris P. Papageorgiou
  • Ioanna Kefala
  • George Papadakis
  • Electra Gizeli
  • Stavros Chatzandroulis
  • George KokkorisEmail author
  • Angeliki TserepiEmail author
Research Paper


The design and fabrication of a continuous-flow μPCR device with very short amplification time and low power consumption are presented. Commercially available, 4-layer printed circuit board (PCB) substrates are employed, with in-house designed yet industrially manufactured embedded Cu micro-resistive heaters lying at very close distance from the microfluidic network, where DNA amplification takes place. The 1.9-m-long microchannel in combination with desirably high flow velocities (for fast amplification) challenged the robustness of the sealing that was overcome with the development of a novel bonding method rendering the microdevice robust even at extreme pressure drops (12 bars). The proposed fabrication methods are PCB compatible, allowing for mass and reliable production of the μPCR device in the established PCB industry. The μPCR chip was successfully validated during the amplification of two different DNA fragments (and with different target DNA copies) corresponding to the exon 20 of the BRCA1 gene, and to the plasmid pBR322, a commonly used cloning vector in E. coli. Successful DNA amplification was demonstrated at total reaction times down to 2 min, with a power consumption of 2.7 W, rendering the presented μPCR one of the fastest and lowest power-consuming devices, suitable for implementation in low-resource settings. Detailed numerical calculations of the DNA residence time distributions, within an acceptable temperature range for denaturation, annealing, and extension, performed for the first time in the literature, provide useful information regarding the actual on-chip PCR protocol and justify the maximum volumetric flow rate for successful DNA amplification. The calculations indicate that the shortest amplification time is achieved when the device is operated at its enzyme kinetic limit (i.e., extension rate).

Graphical abstract


MicroPCR Continuous-flow PCB substrates Computational fluid dynamics Heat transport Residence time distribution 



The authors would like to thank Drs. S.E. Kakambakos and P.S. Petrou at IPRETEA, NCSR “Demokritos,” for providing access to their roll laminator.

Funding information

This research was financially supported by the (1) FP7 “Love Wave Fully Integrated Lab-on-chip Platform for Food Pathogen Detection”—LOVE FOOD project (Contract No 317742)—and (2) Horizon 2020-EU 2.1.1, Project ID: 68768, “LOVEFOOD2Market—A portable MicroNanoBioSystem and Instrument for ultra-fast analysis of pathogens in food: Innovation from LOVE-FOOD lab prototype to a pre-commercial instrument” (

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2019_1911_MOESM1_ESM.pdf (515 kb)
ESM 1 (PDF 514 kb)
216_2019_1911_MOESM2_ESM.flv (3 mb)
ESM 2 (FLV 3074 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Georgia D. Kaprou
    • 1
    • 2
  • Vasileios Papadopoulos
    • 1
  • Dimitris P. Papageorgiou
    • 1
    • 3
  • Ioanna Kefala
    • 1
  • George Papadakis
    • 4
  • Electra Gizeli
    • 2
    • 4
  • Stavros Chatzandroulis
    • 1
  • George Kokkoris
    • 1
    Email author
  • Angeliki Tserepi
    • 1
    Email author
  1. 1.Institute of Nanoscience and NanotechnologyNCSR DemokritosAgia ParaskeviGreece
  2. 2.Department of BiologyUniversity of CreteHeraklionGreece
  3. 3.Department of Materials Science and EngineeringMassachusetts Institute of TechnologyCambridgeUSA
  4. 4.Institute of Molecular Biology and Biotechnology-FORTHHeraklionGreece

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