Improved metrological capabilities for three-dimensional (3D) measurements of various complex micro- and nanoparts are increasingly in demand. This paper gives an overview of the research activities carried out by the Physikalisch-Technische Bundesanstalt (PTB), the national metrology institute of Germany, to meet this demand. Examples of recent research advances in the development of instrumentation and calibration standards are presented. An ultra-precision nanopositioning and nanomeasuring machine (NMM) has been upgraded with regard to its mirror corner, interferometers and angle sensors, as well as its weight compensation, its electronic controller, its vibration damping stage and its instrument chamber. Its positioning noise has been greatly reduced, e.g., from 1σ = 0.52 nm to 1σ = 0.13 nm for the z-axis. The well-known tactile-optical fibre probe has been further improved with regard to its 3D measurement capability, isotropic probing stiffness and dual-sphere probing styli. A 3D atomic force microscope (AFM) and assembled cantilever probes (ACPs) have been developed which allow full 3D measurements of smaller features with sizes from a few micrometres down to tens of nanometres. In addition, several measurement standards for force, geometry, contour and microgear measurements have been introduced. A type of geometry calibration artefact, referred to as the “3D Aztec artefact”, has been developed which applies wet-etched micro-pyramidal marks for defining reference coordinates in 3D space. Compared to conventional calibration artefacts, it has advantages such as a good surface quality, a well-defined geometry and cost-effective manufacturing. A task-specific micro-contour calibration standard has been further developed for ensuring the traceability of, e.g., high-precision optical measurements at microgeometries. A workpiece-like microgear standard embodying different gear geometries (modules ranging from 0.1 mm to 1 mm) has also been developed at the Physikalisch-Technische Bundesanstalt.

A new design for a single-use disposable pneumatic microgripper is presented in this paper. It enables very cost-effective batch microfabrication in SU-8 with a single lithography mask by shifting manufacturing complexity into reusable components. An optically readable force sensor with potential to be used in a feedback loop has been integrated in order to enable gripping with a controlled force. The sensors are first examined separately from the gripper and exhibit good linearity. The gripper function utilizes the disposable gripper element together with a reusable gripper fixture. During experiments, the pneumatically actuated microgripper can vary the gripping force within a range of a few mN (up to 5.7 mN was observed). This microgripper is planned to be used in a liquid environment for gripping larger aggregates of cells in combination with the patch clamp technique. This approach will allow Langerhans islets suspended in an electrolyte solution to be grasped and held during electrophysiological measurements without cell damage.

During the past decade, piezo-resistive cantilever type silicon microprobes for high-speed roughness measurements inside high-aspect-ratio microstructures, like injection nozzles or critical gas nozzles have been developed. This article summarizes their metrological properties for fast roughness and shape measurements including noise, damping, tip form, tip wear, and probing forces and presents the first results on the measurement of mechanical surface parameters. Due to the small mass of the cantilever microprobes, roughness measurements at very high traverse speeds up to 15 mm/s are possible. At these high scanning speeds, considerable wear of the integrated silicon tips was observed in the past. In this paper, a new tip-testing artefact with rectangular grooves of different width was used to measure this wear and to measure the tip shape, which is needed for morphological filtering of the measured profiles and, thus, for accurate form measurements. To reduce tip wear, the integrated silicon tips were replaced by low-wear spherical diamond tips of a 2 µm radius. Currently, a compact microprobe device with an integrated feed-unit is being developed for high-speed roughness measurements on manufacturing machines. First measurements on sinusoidal artefacts were carried out successfully. Moreover, the first measurements of the elastic modulus of a polymer surface applying the contact resonance measurement principle are presented, which indicates the high potential of these microprobes for simultaneous high-speed roughness and mechanical parameter measurements.

Stimuli-responsive hydrogels can be used to convert miniature pressure sensors into novel chemomechanical sensors via confinement of the hydrogel sample between a porous membrane and a piezoresistive diaphragm. Chemomechanical sensors could prove beneficial in a variety of applications, including continuous monitoring of bioreactors and biomedical systems. In this study, one hydrogel composition with a high sensitivity to changes in pH was tested in two different chemomechanical sensors in order to compare the data obtained from each sensor design. In the first and older chemomechanical sensor design, a prefabricated hydrogel sample is loaded into the sensor chamber using a screw-on cap. In the newer sensor design, a thinner hydrogel is synthesized in situ and is held in place by a silicon boss that is mechanically connected to a piezoresistive diaphragm. The newer design results in a decreased chemomechanical sensor response time (by 60 times), and maintains a high sensitivity to changes in environmental stimuli.

To improve the predictive value of in vitro experimentation, the use of 3D cell culture models, or organoids, is becoming increasingly popular. However, the current equipment of life science laboratories has been developed to deal with cell monolayers or cell suspensions. To handle 3D cell aggregates and organoids in a well-controlled manner, without causing structural damage or disturbing the function of interest, new instrumentation is needed. In particular, the precise and stable positioning in a cell bath with flow rates sufficient to characterize the kinetic responses to physiological or pharmacological stimuli can be a demanding task. Here, we present data that demonstrate that microgrippers are well suited to this task. The current version is able to work in aqueous solutions and was shown to position isolated pancreatic islets and 3D aggregates of insulin-secreting MIN6-cells. A stable hold required a gripping force of less than 30 μN and did not affect the cellular integrity. It was maintained even with high flow rates of the bath perfusion, and it was precise enough to permit the simultaneous microfluorimetric measurements and membrane potential measurements of the single cells within the islet through the use of patch-clamp electrodes.