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Research Papers: Micro/Nanoscale Heat Transfer

High Throughput Cell-Free Extraction of Plasma by an Integrated Microfluidic Device Combining Inertial Focusing and Membrane

[+] Author and Article Information
Jun Zhang

School of Mechanical Engineering,
Nanjing University of Science and Technology,
Nanjing 210094, China;
School of Mechanical, Materials and
Mechatronic Engineering,
University of Wollongong,
Wollongong, NSW 2522, Australia
e-mail: junzhang@njust.edu.cn

Sheng Yan

School of Mechanical, Materials and
Mechatronic Engineering,
University of Wollongong,
Wollongong, NSW 2522, Australia
e-mail: sy034@uowmail.edu.au

Dan Yuan

School of Mechanical, Materials and
Mechatronic Engineering,
University of Wollongong,
Wollongong, NSW 2522, Australia
e-mail: dy983@uowmail.edu.au

Gursel Alici

School of Mechanical, Materials and
Mechatronic Engineering,
University of Wollongong,
Wollongong, NSW 2522, Australia
e-mail: gursel@uow.edu.au

Nam-Trung Nguyen

Queensland Micro and Nanotechnology Centre,
Griffith University,
Brisbane, QLD 4111, Australia
e-mail: nam-trung.nguyen@griffith.edu.au

Weihua Li

School of Mechanical, Materials and
Mechatronic Engineering,
University of Wollongong,
Wollongong, NSW 2522, Australia
e-mail: weihuali@uow.edu.au

1Corresponding author.

Presented at the 2016 ASME 5th Micro/Nanoscale Heat & Mass Transfer International Conference. Paper No. MNHMT2016-6533.Contributed by the Heat Transfer Division of ASME for publication in the JOURNAL OF HEAT TRANSFER. Manuscript received March 30, 2016; final manuscript received December 18, 2016; published online February 23, 2017. Assoc. Editor: Chun Yang.

J. Heat Transfer 139(5), 052404 (Feb 23, 2017) (7 pages) Paper No: HT-16-1162; doi: 10.1115/1.4035588 History: Received March 30, 2016; Revised December 18, 2016

Plasma is a host of numerous analytes such as proteins, metabolites, circulating nucleic acids (CNAs), and pathogens, and it contains massive information about the functioning of the whole body, which is of great importance for the clinical diagnosis. Plasma needs to be completely cell-free for effective detection of these analytes. The key process of plasma extraction is to eliminate the contamination from blood cells. Centrifugation, a golden standard method for blood separation, is generally lab-intensive, time consuming, and even dangerous to some extent, and needs to be operated by well-trained staffs. Membrane filtration can filter cells very effectively according to its pore size, but it is prone to clogging by dense particle concentration and suffers from limited capacity of filtration. Frequent rinse is lab-intensive and undesirable. In this work, we proposed and fabricated an integrated microfluidic device that combined particle inertial focusing and membrane filter for high efficient blood plasma separation. The integrated microfluidic device was evaluated by the diluted (×1/10, ×1/20) whole blood, and the quality of the extracted blood plasma was measured and compared with that from the standard centrifugation. We found that the quality of the extracted blood plasma from the proposed device can be equivalent to that from the standard centrifugation. This study demonstrates a significant progress toward the practical application of inertial microfluidics with membrane filter for high-throughput and highly efficient blood plasma extraction.

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Figures

Grahic Jump Location
Fig. 1

Membrane filters in three typical configurations: (a) filter-on-bottom, (b) filter-on-top, and (c) filter-on-side. In the filter-on-bottom configuration, the maximum possible volume of collected plasma is far less than the volume of filter chamber Vchamber; for filter-on-top and filter-on-side configurations, the maximum volume of extracted plasma is 1.22Vchamber. The green dashed arrows indicate the flow direction of the bloodstream.

Grahic Jump Location
Fig. 2

Fabrication of the integrated inertial-membrane microfluidic device. (a) Exploded view of the integrated inertial-membrane microfluidic plasma extractor. This hybrid device consists of parallelized inertial microfluidics and membrane filter with filter-on-top configuration; membrane filter with pore size of 450 nm is suppressed and sealed by two pairs of PMMA slabs and double-sided adhesive tapes. (b) Assembled view of the integrated inertial-membrane device; (c) photo of the fabricated integrated microfluidic device. Three ports are connected to the macroscale world by steel and plastic tube. One is the port for the input of the diluted whole blood, and the other two correspond to pure plasma and blood cells collection, respectively.

Grahic Jump Location
Fig. 3

Schematics of blood plasma extraction in the microfluidic device integrating inertial focusing in the serpentine channel and membrane filter. The inertial filtration in the serpentine channel can get rid of a majority of blood cells, and the series-connected membrane filter further filtrates the remaining cells, leaving completely cell-free blood plasma collected.

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Fig. 4

(a) The images of blood sample and blood plasma sample obtained from different methods: (i) the whole blood diluted ×1/10 by PBS; (ii) after inertial filtration only; (iii) after inertial-membrane filtration; (iv) after the standard centrifugation. (b) Their corresponding microscopic images under the hemocytometer.

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Fig. 5

The comparison of filtration efficiency from different methods on different items: (a) RBCs depletion ratio; (b) WBCs depletion ratio; (c) PLTs depletion ratio; and (d) hemoglobin depletion ratio. The whole blood is diluted by 1/10 with PBS. The standard centrifugation was conducted at 1250× g for 15 min at room temperature. Inertial microfluidic channels alone and the integrated inertial membrane device were operated at a flow rate of 2.8 ml/min.

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