Microwave Microfabricated Sensor Dedicated to the Dielectric Characterization of Biological Microtissues

Abstract

Microwave dielectric spectroscopy is a promising technique that allows intracellular, non-invasive, label-free and cost-effective biological studies. To complement the sensing possibilities of this technique at this frequency range, which have been previously demonstrated at the single cell, cellular suspensions and organs levels, a microwave-based sensor is designed, fabricated and evaluated to dielectrically characterize 3D biological microtissues. Such a biological model is indeed of high interest for biological investigations, as it constitutes an intermediate entity between 2D cell cultures and organs, exhibiting a biological response close to the one obtained with tissue physiology. The proposed sensor here the development of one of the first microfabricated device for spheroids studies. A discussion on the way of analyzing the data is proposed thanks the measurements of different fixed spheroids and polystyrene beads.

Dielectric Spectroscopy: Revealing the True Colors of Biological Matter

“…Moreover, melanomas (skin cancers) have been studied directly in vivo and can be detected using microwave spectroscopy with a sensor in contact with the skin of the subject, as represented in the fourth image of Figure 9 [27]. Finally, the dielectric characterization of microtissue (3D cell aggregates as a model for cancer tissue) is emerging with the device represented in the middle of Figure 9 [19], [28]. In conclusion, CPW allows studies in multiple bio-sample scales as summarized in Figure 9.…”

“…In conclusion, CPW allows studies in multiple bio-sample scales as summarized in Figure 9. [19], [23], [27], [28], [29].…”

RF sensor dedicated to the dielectric characterization of spheroids between 500 MHz and 20 GHz

“…Figure 2c presents the obtained device. The second and final step corresponds to the elaboration of the fluidic walls and the two reservoirs placed on either side of the biosensor with a 500-μm-thick SU8-3050 layer deposited by gravity and then exposed and developed [11,12]. The gravity method consists of manually depositing 6 g of SU8-3050 photoresist on the wafer, followed by baking with a slow temperature ramp up to 95 ∘ C (then leveling off for 11 h and naturally descending to room temperature) before carrying out the exposure at 365 nm with an energy of 3.6 J/cm 2 , followed by the post-exposure bake (with temperature ramp up to 95 ∘ C and a 1 hour plateau) and finally the development for about 45 min.…”

“…With a contrast method using a reference measurement, C ref and G ref , the specific influence of the studied object can be decorrelated from the culture medium in the form of ΔC and ΔG calculated with equations ( 1) and ( 2), respectively. The raw data, C DUT , G DUT , C ref , and G ref , and the standard deviations of the contrasts are given in [12] and [11], respectively.…”

Interests of Microwave Dielectric Spectroscopy for biological characterizations

“…Due to its non-destructive and non-invasive characteristics and combined to its large scalability to various biological elements to be analyzed, it makes it particularly attractive. The sensing capability has already been demonstrated from single cells [1,2] to cell suspensions [3,4] as well as from microtissues [5] up to tissues [6] for various applications. It may be applied to the quantification of cells, their discrimination [4], as well as to the monitoring of cells subjected to physical or chemical stimuli in real time or in time lapse with a wide range of temporal resolution (from microseconds to day and more), such as electrochemotherapy studies, drug screening and personalized medicine.…”