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Particle/Cell Separation on Microfluidic Platforms Based on Centrifugation

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Particle/Cell Separation on Microfluidic Platforms Based on Centrifugation Microfuid Nanofuid (2017) 21:102 DOI 10.1007/s10404-017-1933-4 REVIEW Particle/cell separation on microfuidic platforms based on centrifugation effect: a review Wisam Al‑Faqheri1 · Tzer Hwai Gilbert Thio2 · Mohammad Ameen Qasaimeh3 · Andreas Dietzel4 · Marc Madou5 · Ala’aldeen Al‑Halhouli1 Received: 5 December 2016 / Accepted: 6 May 2017 © Springer-Verlag Berlin Heidelberg 2017 Abstract Particle/cell separation in heterogeneous mix- space on the platform is the main disadvantage, especially tures including biological samples is a standard sample when high sample volume is required. On the other hand, preparation step for various biomedical assays. A wide inertial microfuidics (spiral and multi-orifce) showed range of microfuidic-based methods have been pro- various advantages such as simple design and fabrication, posed for particle/cell sorting and isolation. Two promis- the ability to process large sample volume, high through- ing microfuidic platforms for this task are microfuidic put, high recovery rate, and the ability for multiplexing for chips and centrifugal microfuidic disks. In this review, we improved performance. However, the utilization of syringe focus on particle/cell isolation methods that are based on pump can reduce the portability options of the platform. In liquid centrifugation phenomena. Under this category, we conclusion, the requirement of each application should be reviewed particle/cell sorting methods which have been carefully considered prior to platform selection. performed on centrifugal microfuidic platforms, and iner- tial microfuidic platforms that contain spiral channels and Keywords Microfuidic platforms · Cells separation · multi-orifce channels. All of these platforms implement Particle separation · Lab-on-a-chip · Lab-on-a-disk · a form of centrifuge-based particle/cell separation: either Centrifugal effect physical platform centrifugation in the case of centrifu- gal microfuidic platforms or liquid centrifugation due to Dean drag force in the case of inertial microfuidics. Cen- 1 Introduction trifugal microfuidic platforms are suitable for cases where the preparation step of a raw sample is required to be inte- Particle and cell isolation and analysis have drawn more grated on the same platform. However, the limited available and more interest due to its perceived importance in many different felds and applications (Sajeesh and Sen 2014). In biomedical and biological research, the ability to iso- * Ala’aldeen Al‑Halhouli late specifc particles and cells from a heterogeneous back- [email protected] ground is considered a key tool for the study of individual cells or particles. This technology has resulted in great dis- 1 NanoLab, School of Applied Technical Sciences, German Jordanian University, Amman, Jordan coveries in cell biology and could be utilized to precisely predict a patient’s health status (Tomlinson et al. 2013; 2 Faculty of Engineering and Quantity Surveying, INTI International University, 71800 Nilai, Negeri Sembilan, Sajeesh and Sen 2014). A case in point is the development Malaysia of methods to isolate circulating tumor cells (CTCs). CTCs 3 Division of Engineering, New York University Abu Dhabi, are rare cells that originate from primary cancer tumors and Abu Dhabi, United Arab Emirates travel through the blood to other sites. This is how cancer 4 Institut fur Mikrotechnik, Technische Universität spreads to secondary sites and organs in the body. CTCs Braunschweig, Braunschweig, Germany were frst observed in 1869 by Ashworth (1869) and have 5 Department of Biomedical Engineering, University become a topic of keen interest again in the mid 1990’s. of California Irvine, Irvine, CA, USA The isolation of CTCs can be called “liquid biopsy” as it 1 3 102 Page 2 of 23 Microfuid Nanofuid (2017) 21:102 refects important and early information about tumor status is focused only on particle/cell isolation methods that and progress. Other than in the feld of cell biology, the use are based on centrifugation approaches. Centrifugation of particle/cell separation has been applied to other appli- approaches presented include methods that utilize the phys- cations including the separation of magnetic particles from ical centrifugation process on microfuidic platforms, and a background mixture (Kirby et al. 2012), separation and the approaches that utilize liquid centrifugation effects due observation of bacteria from host blood cells (Hou et al. to Dean effect for cell/particle separation. The platforms 2015), malaria enrichment (Warkiani et al. 2015b), and reviewed include the microfuidic CD, and platforms with separation of DNA (Zhao et al. 2015). spiral microfuidics and multi-orifce microfuidics. For a The demand for compact, inexpensive, disposable, and clear view of the categories, please refer to Fig. 1. high throughput devices that can be implemented for parti- cle/cell separation has led many researchers to consider the various advantages of microfuidic platforms (Burger et al. 2 Centrifugal‑base microfuidics for particle/cell 2012a). The ability of microfuidic platforms to manipu- isolation late small amounts of fuid (on the scale of microliters and below) in micromachined channels has signifcantly The frst step in almost any particle/cell-based research is decreased the required volumes of samples and reagents. the isolation and purifcation of the particles/cells from raw Although microfuidic devices do feature many advantages, samples such as whole blood or serum. This frst step is an a challenge comes about when large sample volumes must important one that needs to produce results in high purity, be processed (few milliliters) to increase the chance of iso- high recovery rates, and high viability numbers (please lating rare cells such as CTCs (Amasia and Madou 2010). refer to the defnitions of these three terms in Sect. 1). Vari- Furthermore, in most cases some type of enrichment/con- ous techniques have been implemented to perform particle/ centration step is often required. cell isolation and purifcation on microfuidic platforms. In Various microfuidic methods and procedures have been this review, these methods and techniques will be presented developed for the isolation of targeted particles and/or cells and the advantages and disadvantages of each method will based on their unique characteristics such as geometry, be highlighted. According to an extensive review for cur- physical, chemical, or genetic properties. The proposed rently available isolation methods, both centrifugal micro- microfuidic platforms fall under one of two categories fuidic platforms and inertial microfuidic platforms have according to the operation mechanism: stationary micro- implemented some form of liquid centrifugation/spinning fuidics, also known as lab-on-chip (LOC) or centrifu- phenomenon to separate particles/cells from heterogeneous gal microfuidics, more commonly known as lab-on-disk backgrounds. For the centrifugal microfuidic platform, the (LOD). Under the LOD category, different passive and whole platform is spun with computer-controlled motors to active methods were proposed for particle/cell sorting and perform different separation methods. On the other hand, isolation. On the other hand, LOC methods mainly rely inertial microfuidic platforms utilize special structure of on the inertial effect for particle/cell manipulation. These microchannel such as curved channels or channels with methods have the advantages of high throughput, simple sudden expansion–contraction arrays to generate secondary design, easy operation, and passive activation without the centrifugation fow to separate particles/cells based on their need for external force for particle/cell manipulation. The physical properties. different isolation methods are usually evaluated by crite- The next section of this paper is divided into two main ria such as purity, recovery rate, and viability (Tomlinson sections: centrifugal microfuidic platforms and inertial et al. 2013). Purity represents the degree of contamination microfuidic platforms (see Fig. 1). In the frst section, of the recovered targeted cells with unwanted background the separation methods are classifed into passive meth- cells/particles. Recovery rate refects the ratio of number of ods (separation without the need for an additional external recovered targeted cells to the number of cells in the origi- force) and active methods (separation using an external nal sample, and viability is the number of recovered live force). In the following section, i.e., inertial microfuidics and heathy cells, which is very important for subsequent methods, the methods are all passive, and the classifcation cell analysis stages. Therefore, ideal cell isolation methods is based only on channel structure. The methods rely on should have short processing time, with high recovery and either spiral or multi-orifce channels to execute particles/ purity rates that result in viable cells. cells separation. Many recent detailed reviews are available that high- light available methods for particle/cell isolation with dif- 2.1 Centrifugal microfuidic platforms ferent types of microfuidic platforms (Warkiani et al. 2015c; Hyun and Jung 2014; Tomlinson et al. 2013; Burger Centrifugal microfuidic platforms are circular-shaped et al. 2012a; Sajeesh and Sen 2014). However, this review platforms containing a network of microchannels and 1 3 Microfuid Nanofuid (2017) 21:102 Page 3 of 23 102 Fig. 1 Cell separation methods on microfuidic platform based on License, and multi-orifce
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