Integrating advanced functionality in a microfabricated high-throughput fluorescent-activated cell sorter

Wolff, Anders; Perch-Nielsen, Ivan R.; Larsen, Ulrik; Friis, Pia; Goranović, Goran; Poulsen, Claus; Kutter, Jörg Peter; Telleman, Pieter

doi:10.1039/b209333b

Cited by 339 publications

(283 citation statements)

References 28 publications

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“…A final consideration is that specific sorting methodologies may perform better when the cells are present in high or low concentrations and should reflect the purpose of that particular device. Microfluorescence-activated cell sorters (µFACSs) operate on the basic principle that a fluorescence signal from a stained cell triggers the operation of valves to control flow switching (13). These devices can separate fluorescent beads in a complex cell sample at a rate of ~12,000 cells/s, and 100-fold enrichments of bead concentration can be obtained.…”

Section: Cell Sortingmentioning

confidence: 99%

Chemical Analysis of Single Mammalian Cells with Microfluidics

Price¹,

Culbertson²

2007

Anal. Chem.

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of Single Mammalian Cells with Microfluidics C ells are the fundamental building blocks of life. All basic physiological functions of multicellular organisms reside ultimately in the cell. The misregulation of cellular physiology results in disease at the organism level. Thus, comprehending cell physiology is key to understanding and curing diseases. Many physiological processes can be studied using populations of cells. Others occur either on short timescales (e.g., kinase signaling cascades) or nonsynchronously (e.g., response to an external chemical gradient), so that taking a population average will not lead to an understanding of how the cellular chemistry occurs. These types of processes require single-cell analysis, and thus discretion must be exercised when deciding under which circumstances bulk versus singlecell analyses are more appropriate (1). In addition, many diseases like cancer start with a single cell; therefore, if one would like to find the rare mutations in populations of cells that herald the inception of a disease, then cells must be examined individually.Probing behavior at the single-cell level, however, is a very challenging task, primarily because of the small sample volume, the low abundance of material, and the fragile nature of the cell itself. Analyzing the contents of a single cell requires sensitive detection techniques and handling procedures that do not stress or damage it. Additionally, no proper blank exists that can be used, so truly quantitative studies are difficult. Intense interest in single-cell physiology, however, is driving the analytical and biomedical engineering fields to improve the technology for examining cells. One of the most popular and promising areas is lab-on-a-chip devices to manipulate and analyze single cells.Since Jorgenson's groundbreaking work in 1989, CE has been used to examine the contents of single cells (2-4). However, many procedures for cell injection and lysis are time-consuming, and accuracy and reproducibility rely heavily on the skill of the researcher. Furthermore, the limited number of architectures provided by microbore tubing and its relatively large volume restrict the types of processes that can be investigated. Conversely, microfluidics, or lab-on-a-chip technology, offers a versatile format in which biological cells can be analyzed.These miniaturized devices provide several analytical and operational advantages over conventional macroscale systems (5, 6). Microfluidic architectures provide precise spatial control over reagents and samples, are capable of fast analysis times, can be automated, and can precisely manipulate picoliter volumes of material without dilution. In addition, microfluidic systems are amenable to many different detection schemes, can be manufactured from many different materials at relatively low cost, allow flexibility of design, and provide the capability of integrating a series of multiple tasks (sample preparation, mixing, separation, etc.) in both serial and parallel schemes. Portable versions of these sys...

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Section: Cell Sortingmentioning

confidence: 99%

Chemical Analysis of Single Mammalian Cells with Microfluidics

Price¹,

Culbertson²

2007

Anal. Chem.

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“…This design is simple and easily fabricated, leading several researchers to imitate it. 9,10,[15][16][17][18][19][20][21][22][23][24][25][26][27] Unfortunately, the sample still comes into contact with the top and the bottom of the channel, which necessitates the addition of a dynamic or covalent coating to mitigate the propensity for fouling. [8][9][10][11]25 Also, cells and particles can appear at any depth from the top to the bottom of the channel, so high numerical aperture optics still cannot be used.…”

Section: Introductionmentioning

confidence: 99%

Two simple and rugged designs for creating microfluidic sheath flow

et al. 2008

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A simple design capable of 2-dimensional hydrodynamic focusing is proposed and successfully demonstrated. In the past, most microfluidic sheath flow systems have often only confined the sample solution on the sides, leaving the top and bottom of the sample stream in contact with the floor and ceiling of the channel. While relatively simple to build, these designs increase the risk of adsorption of sample components to the top and bottom of the channel. A few designs have been successful in completely sheathing the sample stream, but these typically require multiple sheath inputs and several alignment steps. In the designs presented here, full sheathing is accomplished using as few as one sheath input, which eliminates the need to carefully balance the flow of two or more sheath inlets. The design is easily manufactured using current microfabrication techniques. Furthermore, the sample and sheath fluid can be subsequently separated for recapture of the sample fluid or re-use of the sheath fluid. Designs were demonstrated in poly(dimethylsiloxane) (PDMS) using soft lithography and poly(methyl methacrylate) (PMMA) using micromilling and laser ablation.

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“…One example of a particularly important application is the development of a flow cytometer on a chip [1][2][3][4][5][6][7][8][9][10]. For such systems to work efficiently, it is important to be able to confine the sample into a small, spatially well-defined volume, giving as small a probe volume as possible for the detector.…”

Section: Introductionmentioning

confidence: 99%

“…8,9]. However, this technique has drawbacks: focusing is relatively easy to achieve in one dimension, but complex fabrication schemes are required to achieve two-dimensional focusing [6,7]. For this to work, very accurate control of flow rates is required, and since this type of focusing acts on the fluid rather than the particles, small particles and molecules can diffuse from the sample stream into the sheath.…”

Section: Introductionmentioning

confidence: 99%

“…The concept of DEP is particularly attractive as it enables non-contact manipulation of particles such as cells in solution by high frequency electric fields [3], and characterisation of their passive dielectric properties [4][5][6][7][8]. If 3D electrode arrays are employed, interaction with walls or unspecific adsorption of particles may be avoided.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

3D focusing of nanoparticles in microfluidic channels

Morgan

Holmes

Green

2003

IEE Proc., Nanobiotechnol.

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Dynamic focusing of particles can be used to centre particles in a fluid stream, ensuring the passage of the particles through a specified detection volume. This paper describes a method for focusing nanoparticles using dielectrophoresis. The method differs from other focusing methods in that it manipulates the particles and not the fluid. Experimental focusing is demonstrated for a range of different particle types, and discussed in terms of the operational limits of the device. Dynamic numerical simulations of the particle motion in the device are presented and compared with the experimental results. The potential of the device for nanoparticle control and manipulation in microfluidic chips is discussed.

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Integrating advanced functionality in a microfabricated high-throughput fluorescent-activated cell sorter

Cited by 339 publications

References 28 publications

Chemical Analysis of Single Mammalian Cells with Microfluidics

Chemical Analysis of Single Mammalian Cells with Microfluidics

Two simple and rugged designs for creating microfluidic sheath flow

3D focusing of nanoparticles in microfluidic channels

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