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  • Review Article
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Microfabrication meets microbiology

Key Points

  • Microtechnology — the science of structures with micron or submicron-scale features — is beginning to have an impact on microbiology. Microstructured materials provide a range of capabilities for studying microorganisms because their dimensions match the intrinsic size of cells or collections of cells. Broadly stated, this class of structures offers biologists the ability to control the interface between cells and their chemical and physical environment.

  • Soft lithography is a set of techniques that makes it possible to create and replicate microstructures in various materials that are biocompatible and applicable to the study of microorganisms. These techniques are easy to learn, inexpensive, and are available to microbiologists. Recent advances in soft lithography make it possible to create and replicate structures using standard equipment found in most laboratories.

  • Public foundries at Harvard, Stanford, Caltech and the University of Washington (USA), provide access to equipment for microfabrication and function as mechanisms for disseminating new techniques. Foundries teach scientists the techniques of soft lithography and provide custom-designed microfabricated materials to users at a reasonable price.

  • Soft microstructures have only recently been applied to the study of microorganisms. Examples of applications of these materials to microbiology include: the detection of pathogens, the study of interactions between microbes, microbial culture and isolation, single-cell biochemistry and genetics, and studies on motility, chemotaxis, phototaxis, quorum sensing and population dynamics.

  • Microstructures will have a crucial role in the development of new techniques for studying microorganisms. We believe that these structures will provide new capabilities for improvements in cell culture, the study of bacterial physiology and behavior, and quantitative microbiology. Soft lithographic methods are the most widely used techniques for producing classes of structures in materials that might be of interest to microbiologists.

  • Microfabrication has much to offer microbiology and soft lithography provides a bridge between these two fields. The application of these techniques to specific problems by microbiologists can help to guide the development of new techniques and materials by chemists, physicists and engineers.


This Review summarizes methods for constructing systems and structures at micron or submicron scales that have applications in microbiology. These tools make it possible to manipulate individual cells and their immediate extracellular environments and have the capability to transform the study of microbial physiology and behaviour. Because of their simplicity, low cost and use in microfabrication, we focus on the application of soft lithographic techniques to the study of microorganisms, and describe several key areas in microbiology in which the development of new microfabricated materials and tools can have a crucial role.

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Figure 1: The fabrication of micropatterned slabs of PDMS.
Figure 2: The core techniques of soft lithography.
Figure 3: A method for microcontact printing patterns of bacteria using agarose stamps.
Figure 4: Engineering the shape of bacteria by physical confinement.

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This work was supported by grants from the National Institutes of Health and the Defense Advanced Research Projects Agency. We thank Rich Losick for reading the manuscript and providing insightful comments.

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Correspondence to Douglas B. Weibel or George M. Whitesides.

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Chlamydomonas reinhardtii

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Harvard University Soft Lithography Foundry

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University of Washington's Foundry



The fabrication and application of materials, structures and systems with micron or submicron-scale features.


The region sensed by a cell. The dimensions of this region are usually set by molecular contact, mass transport and diffusion, and range from a few nanometers to perhaps a millimeter.

Soft lithography

A set of techniques that makes microstructures by printing, moulding and embossing using a patterned, elastomeric stamp or mould, and/or a polymeric substrate.

Soft material

A material (especially a polymer) that is pliable, compressible or elastic.

Public foundry

A facility for the fabrication of microstructured materials and systems.

Elastomeric polymer

A soft, compliant, rubber-like polymer.


Typically a transparent substrate with a pattern on its surface defined in an opaque material (chrome metal or ink) used in photolithography.


Poly(dimethylsiloxane). An elastomeric silicone polymer that is commercially available and has properties that make it well suited to applications in microbiology.

Embossed structure

A structure that is moulded in a surface in relief.

Bas-relief structure

A structure that projects away from a surface.

Bas-relief master

Refers to the master copy and, in soft lithography, consists of patterns of a photoreactive polymer on the surface of a silicon wafer or glass slide.


A process used to transfer a pattern from a mask onto a thin film of photosensitive polymer (photoresist) and then onto the surface of a substrate. Photolithography is commonly used in semiconductor fabrication to fabricate integrated circuits.

CAD tool

Computer aided design. A software program used by engineers and designers for drafting two- and three-dimensional structures.


A photoreactive polymer that undergoes chemical changes that lead to changes in physical properties (such as solubility) after exposure to ultraviolet light.

Microfluidic system

A set of channels that have micron-scale dimensions (typically between 5–500 μm), and are used to manipulate fluids.

Spin coating

A process for depositing uniform layers of polymer on a substrate. Rotating the substrate at a high speed spreads the material uniformly over the surface. The viscosity of the material and the rotational velocity of the substrate control the thickness of the layer of material; surface tension flattens the surface of the spun film.


Self assembled monolayers. Monolayer structures formed by the spontaneous self-assembly of alkanethiols on metal surfaces. In SAMs, the thiol groups are bonded covalently to the metal surface, and the non-covalent, intermolecular packing of the alkane chains causes the molecules to arrange into an ordered, two-dimensional crystal or liquid crystal.


A low-density, crosslinked polymer network containing a high-volume fraction of water.

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Weibel, D., DiLuzio, W. & Whitesides, G. Microfabrication meets microbiology. Nat Rev Microbiol 5, 209–218 (2007).

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