MEMS-based sample preparation for molecular diagnostics

Huang, Ying; Mather, Elizabeth L.; Bell, Janice L.; Madou, Marc

doi:10.1007/s00216-001-1191-9

Cited by 182 publications

(151 citation statements)

References 73 publications

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“…8,9 Currently available approaches to on-the-chip sample preparation are based on filtration4 , 8 ,33 or dielectrophoresis (DEP) 34 or require preliminary cell modification steps such as fluorescent labeling35 , 36 or tagging with magnetic beads.37 ,38 The current state of the art of these and other sample preparation methods is the focus of recent reviews. 3,6,7,10 The new leukocyte enrichment method described here has many important advantages over these technologies. It is simple, has no active (moving or otherwise) elements, requires only a small hydrostatic pressure gradient to function, and can be easily manufactured using conventional microfabrication.…”

Section: Resultsmentioning

confidence: 99%

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Biomimetic Autoseparation of Leukocytes from Whole Blood in a Microfluidic Device

et al. 2004

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Leukocytes comprise less than 1% of all blood cells. Enrichment of their number, starting from a sample of whole blood, is the required first step of many clinical and basic research assays. We created a microfluidic device that takes advantage of the intrinsic features of blood flow in the microcirculation, such as plasma skimming and leukocyte margination, to separate leukocytes directly from whole blood. It consists of a simple network of rectangular microchannels designed to enhance lateral migration of leukocytes and their subsequent extraction from the erythrocytedepleted region near the sidewalls. A single pass through the device produces a 34-fold enrichment of the leukocyte-to-erythrocyte ratio. It operates on microliter samples of whole blood, provides positive, continuous flow selection of leukocytes, and requires neither preliminary labeling of cells nor input of energy (except for a small pressure gradient to support the flow of blood). This effortless, efficient, and inexpensive technology can be used as a lab-on-a-chip component for initial whole blood sample preparation. Its integration into microanalytical devices that require leukocyte enrichment will enable accelerated transition of these devices into the field for point-of-care clinical testing.The rapidly expanding field of lab-on-a-chip microanalytical devices promises inexpensive, portable, miniaturized tools that could potentially revolutionize clinical and basic research analyses by dramatically reducing sample size and handling.1 -3 An important application of this technology is the analysis of leukocytes (white blood cells) or their contents, for which these cells must first be isolated from the whole blood sample. [4][5][6][7] Blood is a 45% suspension of cells (erythrocytes, platelets, leukocytes) in plasma. Erythrocytes (red blood cells) constitute the vast majority of all blood cells and are normally ∼1000 times more abundant than leukocytes. Traditionally, several milliliters of whole blood are drawn and then centrifuged in order to separate blood cells of different density. Plasma, platelets, and white and red cells can be separated by this procedure, but it is a labor-, energy-, and time-intensive process that relies on special equipment and requires trained personnel. 8, 9 Many current microanalytical devices have no integrated sample

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Section: Resultsmentioning

confidence: 99%

“…[4][5][6][7] Blood is a 45% suspension of cells (erythrocytes, platelets, leukocytes) in plasma. Erythrocytes (red blood cells) constitute the vast majority of all blood cells and are normally ∼1000 times more abundant than leukocytes.…”

Section: Introductionmentioning

confidence: 99%

Biomimetic Autoseparation of Leukocytes from Whole Blood in a Microfluidic Device

et al. 2004

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“…102 Very few LoC and LoD devices, particularly those that perform molecular diagnostic assays, feature a completely integrated sample preparation system because modular solutions, in which one fluidic feature or hardware component can be used for multiple functions, are rarely available. However, to develop a truly user-friendly and portable total analysis system, sample preparation is key.…”

Section: Sample Preparationmentioning

confidence: 99%

Lab-on-a-CD: A Fully Integrated Molecular Diagnostic System

et al. 2016

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The field of centrifugal microfluidics has experienced tremendous growth during the past 15 years, especially in applications such as lab-on-a-disc (LoD) diagnostics. The strength of LoD systems lies in its potential for development into fully integrated sample-to-answer analysis systems. This review highlights the technologies necessary to develop the next generation of these systems. In addition to outlining valving and other fluid-handling operations, we discuss the recent advances and future outlook in four categories of LoD processes: reagent storage, sample preparation, nucleic acid amplification, and analyte detection strategies.

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“…17,49,61,87,106,110 Alternately, other methods can examine local domains. 20,42,51,54,79,80,102,103,111 Lithographic fabrication techniques have been used to develop tools to study how cell shape is regulated by the attachment and spreading of individual cells. 9,25,55,64,66,67,73,75,92 .…”

Section: Nano-and Microtechnology To Address the Cytoskeletonmentioning

confidence: 99%

Nanoscale Intracellular Organization and Functional Architecture Mediating Cellular Behavior

LeDuc

Bellin

2006

Ann Biomed Eng

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Abstract-Cells function based on a complex set of interactions that control pathways resulting in ultimate cell fates including proliferation, differentiation, and apoptosis. The interworkings of this immensely dense network of intracellular molecules are influenced by more than random protein and nucleic acid distribution where their interactions culminate in distinct cellular function. By probing the design of these biological systems from an engineering perspective, researchers can gain great insight that will aid in building and utilizing systems that are on this size scale where traditional large-scale rules may fail to apply. The organized interaction and gradient distribution in intracellular space imply a structural architecture that modulates cellular processes by influencing biochemical interactions including transport and binding-reactions. One significant structure that plays a role in this modulation is the cell cytoskeleton. Here, we discuss the cytoskeleton as a central and integrating functional structure in influencing cell processes and we describe technology useful for probing this structure. We explain the nanometer scale science of cytoskeletal structure with respect to intracellular organization, mechanotransduction, cytoskeletal-associated proteins, and motor molecules, as well as nano-and microtechnologies that are applicable for experimental studies of the cytoskeleton. This biological architecture of the cytoskeleton influences molecular, cellular, and physiological processes through structured multimodular and hierarchical principles centered on these functional filaments. Through investigating these organic systems that have evolved over billions of years, understanding in biology, engineering, and nanometer-scaled science will be advanced.

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MEMS-based sample preparation for molecular diagnostics

Cited by 182 publications

References 73 publications

Biomimetic Autoseparation of Leukocytes from Whole Blood in a Microfluidic Device

Biomimetic Autoseparation of Leukocytes from Whole Blood in a Microfluidic Device

Lab-on-a-CD: A Fully Integrated Molecular Diagnostic System

Nanoscale Intracellular Organization and Functional Architecture Mediating Cellular Behavior

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