An optimized measurement chamber for cantilever array measurements in liquid incorporating an automated sample handling system

Abstract

Micro-and nanomechanical analytical devices for diagnostics require small sample volumes, and stable and efficient clamping of the sensors for optimized bioassays. A fully automated device for the readout of the dynamic and static response of cantilevers in a physiological liquid environment including a sample handling system is presented. The device provides sequential readout of the static and dynamic mode providing the best signal to noise ratio for each individual cantilever. In the dynamic mode, it is possible to measure up to the 16 th flexural resonance mode of vibration of a 500 μm long and 1 μm thick cantilever. The automated sample handling system enables the local injection of sub microliter volumes of sample with excellent reproducibility. Data demonstrating the response of the cantilevers to external stimuli highlight the sensitivity of the device and the importance of the use of reference cantilevers to decouple biologically relevant metrics from environmental effects. A specific biomolecular interaction of sensitised nanospheres on cantilever sensors with a mass resolution of~50 picogram in liquid is shown.

Microrheological Coagulation Assay Exploiting Micromechanical Resonators

“…The amplitude and phase spectra of the oscillations were evaluated from the recorded data using a custom LabVIEW software interface. Upgrades on the previously presented device 29 include the following: (1) digitizer with higher resolution (National Instruments PCI-5105, 60 MS/s, 12-bit) to better resolve individual voltage levels of the position sensitive detector (PSD) response, (2) expanded and improved temperature-controlled enclosure, and (3) four remotely controlled syringe pumps housed inside the temperaturecontrolled enclosure. The normalized differential signal of the PSD is acquired at 10 MS/s, and each driving signal frequency is applied for 1 ms. For detailed information on resonance frequency and quality factor evaluation, see Supporting Information.…”

“…For details about the fully automized experimental setup, we refer the reader to ref . Briefly, an array of 8 cantilevers is mounted into a 4 μL measurement chamber that allows liquid exchange through 4 syringe pumps and a microdispensing valve.…”

“…The relatively high injection speed is required for a fast exchange (6 s) of the liquid; otherwise, the reaction between thrombin and fibrinogen would occur before entering the measurement chamber. The mixing occurred automatically 10 μL before the chamber, and this volume has to be pushed 15 μL further to enter the chamber (see design in ref ). To ensure optimal mixing of the solution, different volumes and injection speeds were tested with two different colored solutions, and the final color (a mix of the two) was recorded and analyzed with image-analysis software (see video in ref ).…”

Rapid Label-free Nanotechnological Immunoassay for Analysis of Candidate Malaria Vaccines

“…Synchronised differential readout with in-situ reference probes is mandatory to avoid convolution with external environmental factors. Such differential analysis also eliminates thermal experimental drifts, flow-induced disturbances, and unspecific interactions as present in serum samples (see Figure 1) [1,13,[15][16][17][18][19][20][21][22][23].…”

“…The epitope-specific antibody recognition (panel a) (red antibodies towards UK39 and grey antibodies as unspecific interactions) generates a frequency shift based on the different sensor functionalizations (panel b). Taking the characteristics of the fluid around the sensors and the sensors' dimensions into account, the frequency shifts are converted into a mass addition towards one or the other epitope (panel c)[15,17,20,22,23].…”