A concise review of microfluidic particle manipulation methods

Shuaizhong Zhang, Ye Wang, Patrick Onck & Jaap den Toonder

Particle manipulation is often required in many applications such as bioanalysis, disease diagnostics, drug delivery and self-cleaning surfaces. The fast progress in micro- and nano-engineering has contributed to the rapid development of a variety of technologies to manipulate particles including more established methods based on microfluidics, as well as recently proposed innovative methods that still are in the initial phases of development, based on self-driven microbots and artificial cilia. Here, we review these techniques with respect to their operation principles and main applications. We summarize the shortcomings and give perspectives on the future development of particle manipulation techniques. Rather than offering an in-depth, detailed, and complete account of all the methods, this review aims to provide a broad but concise overview that helps to understand the overall progress and current status of the diverse particle manipulation methods. The two novel developments, self-driven microbots and artificial cilia-based manipulation, are highlighted in more detail.

DOI

Flow with nanoparticle clustering controlled by optical forces in quartz glass nanoslits

Tetsuro Tsuji, Yuki Matsumoto, Satoyuki Kawano

In this paper, we demonstrate nanoparticle flow control using an optical force in a confined nanospace. Using nanofabrication technologies, all-quartz-glass nanoslit channels with a sudden contraction are developed. Because the nanoslit height is comparable to the nanoparticle diameter, the motion of particles is restricted in the channel height direction, resulting in almost two-dimensional particle motion. The laser irradiates at the entrance of the sudden contraction channel, leading the trapped nanoparticles to form a cluster. As a result, the translocation of nanoparticles into the contraction channel is suppressed. Because the particle translocation restarts when the laser irradiation is stopped, we can control the nanoparticle flow into the contraction channel by switching the trapping and release of particles, realizing an intermittent flow of nanoparticles. Such a particle flow control technique in a confined nanospace is expected to improve the functions of nanofluidic devices by transporting a target material selectively to a desired location in the device.

DOI

All-silica microfluidic optical stretcher with acoustophoretic prefocusing

Giovanni Nava, Francesca Bragheri, Tie Yang, Paolo Minzioni, Roberto Osellame, Ilaria Cristiani, Kirstine Berg-Sørensen

Acoustophoresis is a widely reported and used technique for microparticle manipulation and separation. In the study described here, acustophoresis is employed to prefocus the flow (i.e., focusing occurring upstream of the analysis region) in a microfluidic chip intended for optical trapping and stretching. The whole microchip is made of silica with optical waveguides integrated by femtosecond laser writing. The acoustic force is produced by driving an external piezoelectric ceramic attached underneath the microchip at the chip resonance frequency. Thanks to an efficient excitation of acoustic waves in both water and glass, acoustophoretic focusing is observed along the channel length (>40 mm) and it is successfully demonstrated both with polystyrene beads, swollen red blood cell, and cells from mouse fibroblast cellular lines (L929). Moreover, by comparing results of cell stretching measurements, we demonstrate that acoustic waves do not alter the optical deformability of the cells and that the acoustic prefocusing results in a considerable enhancement of throughput in optical stretching experiments.

DOI

The study of spermatozoa and sorting in relation to human reproduction

James Boon Yong Koh, Marcos

In this review article, we seek to provide a link between our understanding of the spermatozoa on the physical aspects and applications involving assisted reproduction, so that future research in this field can be better poised for improving current procedures. A brief discussion is included regarding the difference in the fluid mechanics of a Newtonian and viscoelastic fluid medium. A review is then done on the current microfluidic sorting techniques applicable to spermatozoa, which includes the albumin gradient separation, fluorescence activated flow cytometry, electrophoresis, dielectrophoresis, countercurrent distribution, movement of motile sperms, accumulation at walls, and optical trapping. Common preparation methods for spermatozoa used in assisted reproduction are also introduced. A number of other general particle manipulation methods which could potentially be incorporated for sperm sorting are also discussed.

DOI

A simple and direct reading flow meter fabricated by two-photon polymerization for microfluidic channel

Yi-Jui Liu, Juin-Yi Yang, Yung-Mau Nie, Chun-Hung Lu, Eric Dowkon Huang, Chow-Shing Shin, Patrice Baldeck, Chih-Lang Lin

This study introduces an innovative micromachine that enables precise measurement of the flow rate at the micron scale (μl/min) in microfluidic channel. It is fabricated by the state-of-the-art technique of two-photon polymerization and consists of: a rod-spring, a water-drop-shaped frame, and an indicator situated inside a microfluidic channel. The indicator is deflected by the flowing fluid while restrained by the spring to establish an equilibrium indication according to the flow rate. In the practical tests, the flow successfully agitates the spring in a proper deflection. The relationship between the flow rate and the deflection angle was calibrated.

DOI

In situ seriate droplet coalescence under an optical force

Jin Ho Jung, Kyung Heon Lee, Ghulam Destgeer, Kang Soo Lee, Hyunjun Cho, Byung Hang Ha, Hyung Jin Sung

We demonstrated the induced coalescence of droplets under a highly accurate optical force control. Optical scattering and gradient forces were used to push and trap the droplets prior to coalescence within a microfluidic channel. The behavior of the droplets under the influence of an optical force was predicted using an analytical model that agreed well with the experimental data. The optical gradient force accelerated and decelerated the droplet within the laser beam region, and the drag force acting on the droplet was thoroughly characterized. A description of the optical trap was presented in terms of the momentum transfer from the photons to the droplet, effectively restricting droplet motion inside the microfluidic channel prior to coalescence. A phase diagram was plotted to distinguish between the three regimes of droplet coalescence, including the absence of coalescence, coalescence, and multiple coalescence events. The phase diagram permitted the laser power input and the net flow rate in the microfluidic channel to be estimated. This technique was applied to the synthesis of biodegradable gel microparticles.

DOI

Simple applications of microparticle transportation by tender optical scattering force

Hideharu Kotari, Masahiro Motosuke

This paper provides a novel application of the optical radiation pressure for microfluidic particle transportation without precise focusing or alignment of the laser beam to the device and target. An optical manipulation of particles in a microfluidic platform is highly exploited in life science or biomedical analysis using optical tweezers with the use of a gradient force of the optical radiation pressure. Our method utilizes the other term of the radiation pressure, namely scattering force, to manipulate particles in a microchannel. The migration distance of particle depends on the amount of light received by the particle. Therefore, particle movement with long retention distance can be achieved by large-area irradiation even with low energy density. In our experiments, two proof-of-concept microfluidic chips were designed and investigated; one was a lateral particle sorting using a monolithic microfluidic chip integrated with a planar SU-8 waveguide and beam expander, the other was a vertical sorting using a 10-cm-long polydimethylsiloxane channel with whole-area irradiation. Experimental results show that 1, 2 and 5 μm polystyrene beads can be transported by the optical scattering force and that particle migration is achieved with the irradiated energy density <10 mW/mm2. The present method has practical potential for simple and fuss-free use of the optical radiation pressure without spot focusing or precise alignment process of the laser beam and damage to the device and sample.

DOI

Structured attachment of bacterial molecular motors for defined microflow induction

Mike Woerdemann, Florian Hörner, Cornelia Denz

Bacterial rotational motor complexes that propel flagellated bacteria possess unique properties like their size of a few nanometres and the ability of selfreproduction that have led to various exciting applications including biohybrid nano-machines. One mandatory prerequisite to utilize bacterial nano motors in fluid applications is the ability to transfer force and torque to the fluid, which usually can be achieved by attachment of the bacterial cell to adequate surfaces. Additionally, for optimal transfer of force or torque, precise control of the position down to the single cell level is of utmost importance. Based on a PIV (particle image velocimetry) evaluation of the induced flow of single bacteria,we propose and demonstrate attachment of arbitrary patterns of motile bacterial cells in a fast light-based two-step process for the first time to our knowledge. First, these cells are pre-structured by holographic optical tweezers and then attached to a homogeneous, polystyrene-coated surface. In contrast to the few approaches that have been implemented up to now and which rely on pre-structured surfaces, our scheme allows for precise control on a single bacterium level, is versatile, interactive and has low requirements with respect to the surface preparation.

DOI

Optical separation of droplets on a microfluidic platform

Jin Ho Jung, Kyung Heon Lee, Kang Soo Lee, Byung Hang Ha, Yong Suk Oh, Hyung Jin Sung
This paper describes the optical separation of microdroplets according to their refractive indices. The behavior of the droplets was characterized in terms of the optical force and the hydrodynamic effects present upon illumination of the droplets in a direction normal to the flow direction in a rectangular microfluidic channel. The optical forces acting on the droplets and the resultant droplet trajectories were analyzed and compared with the numerically predicted values. The relationship between the drag force and optical force was examined to understand the system performance properties in the context of screening applications involving the removal of unwanted droplets. Two species of droplets were compared for their photophoretic displacements by varying the illumination intensity. Because the optical forces exerted on the droplets were functions of the refractive indices and sizes of the droplets, a variety of chemical species could be separated simultaneously.
DOI

Image-based algorithm for analysis of transient trapping in single-particle trajectories

Daphne Weihs, Dror Gilad, Moti Seon and Itai Cohen

Particle tracking has become an increasingly useful tool in microfluidics and biophysics, allowing measurement of microrheology, local structure, and flow. We introduce a novel, automated approach to analyze single-particle trajectories with transient elements, based on image-processing approaches and physical analysis of probe motion. In many physical and active biological systems, such as living cells, probe particles experience thermally mediated Brownian motion combined with active transport processes that can lead to transient-trajectories of local diffusion and trapping, punctuated by segments of active transport. Analyzing such a trajectory as a single unit masks the intermittent nature of the motion. Moreover, directly applying the generalized Stokes–Einstein relation in out-of-equilibrium systems is incorrect and returns inaccurate rheological parameters. We present an automated image-processing-based method to identify and segment transient trap-escape trajectories, allowing quantitative analysis of each segment. We define and discuss effects of controlling parameters, such as particle size and camera frame rate. Our algorithm provides a general and automated method to segment and analyze transient elements in trajectories of single particles, which can be applied to many different experiments. Our image-based approach allows identification of trapping segments, unbiased by specific step sizes within those traps or the mechanism driving those steps. As an example, we successfully apply this method to experiments of laser tweezers trapped particles and show that trajectory segmentation allows us to calculate both trap and fluid parameters. We accurately identify a round trap, calculate the trap stiffness at 3.1 pN/μm, and find that significant local heating reduces fluid viscosity.

DOI

Nanomanipulation of single influenza virus using dielectrophoretic concentration and optical tweezers for single virus infection to a specific cell on a microfluidic chip

Hisataka Maruyama, Kyosuke Kotani, Taisuke Masuda, Ayae Honda, Tatsuro Takahata and Fumihito Arai
A major problem when analyzing bionanoparticles such as influenza viruses (approximately 100 nm in size) is the low sample concentrations. We developed a method for manipulating a single virus that employs optical tweezers in conjunction with dielectrophoretic (DEP) concentration of viruses on a microfluidic chip. A polydimethylsiloxane microfluidic chip can be used to stably manipulate a virus. The chip has separate sample and analysis chambers to enable quantitative analysis of the virus functions before and after it has infected a target cell. The DEP force in the sample chamber concentrates the virus and prevents it from adhering to the glass substrate. The concentrated virus is transported to the sample selection section where it is trapped by optical tweezers. The trapped virus is transported to the analysis chamber and it is brought into contact with the target cell to infect it. This paper describes the DEP virus concentration for single virus infection of a specific cell. We concentrated the influenza virus using the DEP force, transported a single virus, and made it contact a specific H292 cell.

DOI

Dielectrophoretically assembled particles: feasibility for optofluidic systems

Khashayar Khoshmanesh, Chen Zhang, Jos L. Campbell, Aminuddin A. Kayani, Saeid Nahavandi, Arnan Mitchell and Kourosh Kalantar-zadeh

This work presents the dielectrophoretic manipulation of sub-micron particles suspended in water and the investigation of their optical responses using a microfluidic system. The particles are made of silica and have different diameters of 600, 450, and 250 nm. Experiments show a very interesting feature of the curved microelectrodes, in which the particles are pushed toward or away from the microchannel centerline depending on their levitation heights, which is further analyzed by numerical simulations. In doing so, applying an AC signal of 12 Vp–p and 5 MHz across the microelectrodes along with a flow rate of 1 μl/min within the microchannel leads to the formation of a tunable band of particles along the centerline. Experiments show that the 250 nm particles guide the longitudinal light along the microchannel due to their small scattering. This arrangement is employed to study the feasibility of developing an optofluidic system, which can be potentially used for the formation of particles-core/liquid-cladding optical waveguides.

DOI

Functional gel-microbead manipulated by optical tweezers for local environment measurement in microchip

Hisataka Maruyama, Toshio Fukuda and Fumihito Arai

A novel on-chip environment measurement with functional gel-microtool was developed. Environment measurement gel-microtool was fabricated by connecting the gel-microbeads impregnated with indicators in a microchip. In this artcle, Bromothymol blue (BTB) and Bromocresol green (BCG) were employed as pH indicators. BTB and BCG have the different indicator range. Rhodamine B is temperature sensitive fluorescent dye and is used for temperature measurement. Gel-microbead is made by salting-out of hydrophilic photo-crosslinkable resin and is manipulated by optical tweezers. Moreover, gel-microbead is polymerized by UV illumination and connected to other gel-microbead under an electrolyte solution. The connection of gel-microbeads is performed by contact of gel-microbeads under UV illumination. Environment measurement gel-microtool with an arbitrary shape is fabricated by connection of the gel-microtool impregnated with arbitrary indicator. Multiple environments measurement gel-microtool included with several indicators is realized by assembly of the gel-microbeads impregnated with different indicators. Environment measurement is performed by detecting the color and the fluorescence intensity of each gel-microbead. We succeeded in the on-chip fabrication of the environment measurement gel-microtools such as circular pH measurement gel-microtool and wide range pH measurement gel-microtool in a microchip.

DOI