Fabricating Silicon Resonators for Analysing Biological Samples

Abstract

The adaptability of microscale devices allows microtechnologies to be used for a wide range of applications. Biology and medicine are among those fields that, in recent decades, have applied microtechnologies to achieve new and improved functionality. However, despite their ability to achieve assay sensitivities that rival or exceed conventional standards, silicon-based microelectromechanical systems remain underutilised for biological and biomedical applications. Although microelectromechanical resonators and actuators do not always exhibit optimal performance in liquid due to electrical double layer formation and high damping, these issues have been solved with some innovative fabrication processes or alternative experimental approaches. This paper focuses on several examples of silicon-based resonating devices with a brief look at their fundamental sensing elements and key fabrication steps, as well as current and potential biological/biomedical applications.

Keywords: biological applications; fabrication; microelectromechanical systems; resonators; silicon.

Figure 1

Examples of different types of silicon-based resonant MEMS applied at the subcellular level. 1–3 are suspended structures of (1) cantilever type (reproduced from [61], with the permission of AIP publishing), (2) bridging type [62] (Copyright Elsevier 2008), and (3) plate type [12] (with granted permission from PNAS). Structures 4 to 6 have integrated channels as in the cases of (4) cantilever type [11] (reprinted by permission from Springer Nature [11] Copyright 2007), (5) bridging type [63] (reproduced with a permission from ACS), and (6) plate type [64] (reproduced with permission from The Royal Society of Chemistry). MEMS squeezers include (7) microgrippers [57] (CC BY license) and (8) fluidics-integrated devices [65] (CC BY license).

Figure 2

Examples of silicon-based resonant MEMS applied at the subcellular level. (A) Suspended channel resonator described by Burg et al. [11] (reprinted by permission from Springer Nature [11] Copyright 2007). (Top-left) the schematic representation of the resonator and SEM image of the cantilever (Top-right). The bottom side of the channel was etched open intentionally for visualizing the fluid conduit. Molecules flow continuously through the channel. Species that have the correct affinity bind to immobilised receptors on the channel walls and accumulate (Middle panel). In another measurement mode (Lower panel), particles flow through the cantilever without binding to the surface. The signal depends on the position of the particle inside the channel (numbers 1 to 3). The exact mass excess of a particle can be quantified by the peak frequency shift induced at the apex. (B) Schematic representation of the cantilever system used by Park et al. to improve the quality factor (50%) and signal-to-noise ratio (5.7-fold) by working at an air–liquid interface [112] (reproduced with permission from The Royal Society of Chemistry). They demonstrated the detection of insulin and monitored enzymatic activity between SOD1 and proteinase K [113]. Figure adapted [112] from with permission from The Royal Society of Chemistry. (C) Microgrippers, described by Tarhan et al., inserted only a very small area of their tips in a solution to perform titration experiments on a DNA bundle. The resonating and sensing MEMS elements working in air provide optimum MEMS performance [57,58,89]. (i) and (ii) are the schematic view (top and side) of the brightfield microscopy image showing tips of the microgripper access to the channel wall with a red solution (iii) (CC BY license).

Figure 3

Examples of silicon-based resonating MEMS technologies for analysing cells. (A) The cantilever-type suspended channel device coupled a constriction located at the apex of the channel, described by Byun et al. [35] (with granted permission from PNAS). The cell (represented as the yellow sphere) is deformed by the 6 μm-wide, 15 μm-deep, and 50 μm-long constriction. The numbers 1 to 5 indicate the trajectory of the cell. The resonant frequency change of the cantilever structure changes with the cell passing in the channel and going through the constriction. (B) Suspended plate resonant sensor described by Park et al. [12] (with granted permission from PNAS), where the cells are cultured on a sensor platform and the increase in mass through cellular growth is measured. The graph on the right monitors a cell division event. Prior to cell division, an individual cell’s growth data (blue line) conforms to an exponential curve fitting. Insets 1–3 show the cell division event. (C) The fluidics-integrated MEMS squeezer device, described by Takayama et al. [65], has only the tips of the device enter the microchannel while the sensing and measurement components are not submerged, allowing simultaneous electrical and mechanical measurements in air (CC BY license).