We demonstrate mass-producible, tetherless microgrippers that can be remotely triggered by temperature and chemicals under biologically relevant conditions. The microgrippers use a selfcontained actuation response, obviating the need for external tethers in operation. The grippers can be actuated en masse, even while spatially separated. We used the microgrippers to perform diverse functions, such as picking up a bead on a substrate and the removal of cells from tissue embedded at the end of a capillary (an in vitro biopsy).actuator ͉ biochemical ͉ robotics ͉ thin films B iological function in nature is often achieved by autonomous organisms and cellular components triggered en masse by relatively benign cues, such as small temperature changes and biochemicals. These cues activate a particular response, even among large populations of spatially separated biological components. Chemically triggered activity is also often highly specific and selective in biological machinery. Additionally, mobility of autonomous biological entities, such as pathogens and cells, enables easy passage through narrow conduits and interstitial spaces.As a step toward the construction of autonomous microtools, we describe mass-producible, mobile, thermobiochemically actuated microgrippers. The microgrippers can be remotely actuated when exposed to temperatures Ͼ40°C or selected chemicals. The temperature trigger is in the range experienced by the human body at the onset of a moderate-to-high fever, and the chemical triggers include biologically benign reagents, such as cell media. Using these microgrippers, we achieved a diverse set of functions, such as picking up beads off substrates and removing cells from tissue samples.Conventional microgrippers are usually tethered and actuated by mechanical or electrical signals (1-6). Recently developed actuation mechanisms using pneumatic (7), thermal (8), and electrochemical triggers (9, 10) have also used tethered operation. Because the functional response of currently available microgrippers is usually controlled through external wires or tubes, direct connections need to be made between the gripper and the control unit. These connections restrict device miniaturization and maneuverability. For example, a simple task such as the retrieval of an object from a tube is challenging at the millimeter and submillimeter scale, because tethered microgrippers must be threaded through the tube. Moreover, many of the schemes used to drive actuation in microscale tools use biologically incompatible cues, such as high temperature or nonaqueous media, which limit their utility. There are novel, untethered tools based on shape memory alloys that use low temperature heating, but they have limited mobility and must rely solely on thermal actuation (11,12). The ability of our gripper design to use biochemical actuation, in addition to thermal actuation, represents a paradigm shift in engineering and suggests a strategy for designing mobile microtools that function in a variety of environments with high specif...

SUMMARY Since the native cellular environment is three dimensional (3D), there is a need to extend planar, micro and nanostructured biomedical devices to the third dimension. Self-folding methods can extend the precision of planar lithographic patterning into the third dimension and create reconfigurable structures that fold or un-fold in response to specific environmental cues. Here, we review the use of hinge-based self-folding methods in the creation of functional 3D biomedical devices including precisely patterned nano to centimeter scale polyhedral containers, scaffolds for cell culture, and reconfigurable surgical tools such as grippers that respond autonomously to specific chemicals.

We describe the use of conventional photolithography to construct three dimensional (3D) thin film scaffolds and direct the growth of fibroblasts into three distinct and anatomically relevant geometries: cylinders, spirals and bi-directionally folded sheets. The scaffolds were micropatterned as twodimensional sheets which then spontaneously assembled into specific geometries upon release from the underlying substrate. The viability of fibroblasts cultured on these self-assembling scaffolds was verified using fluorescence microscopy; cell morphology and spreading were studied using scanning electron microscopy. We demonstrate control over scaffold size, radius of curvature and folding pitch, thereby enabling an attractive approach for investigating the effects of these 3D geometric factors on cell behaviour.

We demonstrate mass-producible, mobile, self-loading microcontainers that can be used to encapsulate both non-living and living objects, thus forming three-dimensionally patterned, mobile microwells.Studies of cells and their function have traditionally been performed on two-dimensional (2D) cell cultures. However, the omission of the third dimension can greatly impact cell behavior by limiting interactions with the surroundings. 1 Microwells in substrates have been developed to address this, but are typically accessible only from one interface; this limitation is especially pronounced in cell culture when the encapsulated cells may experience nutrient deficient conditions due to well geometry and size. 2Researchers continue to add new functionality to microwells, such as making them compatible with high resolution analysis, adding networking channels to facilitate cell-cell interactions, integrating stimulation/measurement devices, and devising methods to generate dense arrays of wells with individually customizable, variable geometry morphologies. 3,4 Also, microwell structures for bioreactors have been designed with porous membrane floors that allow for media perfusion through the well. 5 This allows media to convectively enter the microwell from one interface and exit through another. However, despite the advancements in technology, current microwells essentially only provide a quasi-3D environment, where patterning is limited to 2D and cells are in contact with planar surfaces. 3 Truly 3D encapsulation, where porosity is precisely engineered on all faces in 3D, allows for greater interaction between encapsulated cells and surrounding media.In this communication, we describe photolithographically structured, mobile microcontainers that function like three-dimensionally patterned, mobile microwells. The containers load themselves as they self-assemble from cruciform templates en masse at around 40°C, a temperature low enough to enable parallel loading of biological objects. These containers have porous surfaces and interact with their surroundings in all three dimensions. Additionally, the untethered nature of the cruciforms and containers, coupled with the use of ferromagnetic materials, allows for remote-controlled guidance of both unloaded cruciforms as well as loaded containers. 7 The assembly of the microcontainers is thermally triggered, without the need for any external connections. Photolithography enables the containers to be fabricated with precisely-engineered monodisperse sizes, shapes, and wall porosity. 6 Using self-assembly, 2D templates are transformed into 3D structures with porosity in all dimensions. We demonstrate the self-loading of glass beads, L929 fibroblast cells, and Triops embryos. The loading of biological contents highlights the utility of the low temperature self-loading process.Fabrication of the microcontainers was based on stress-driven assembly using thin film hinges and has been described in detail elsewhere. 8 Briefly, the microcontainers were constructed as 2D cru...