A Multichannel Microfluidic Sensing Cartridge for Bioanalytical Applications of Monolithic Quartz Crystal Microbalance

Abstract

Integrating acoustic wave sensors into lab-on-a-chip (LoC) devices is a well-known challenge. We address this challenge by designing a microfluidic device housing a monolithic array of 24 high-fundamental frequency quartz crystal microbalance with dissipation (HFF-QCMD) sensors. The device features six 6-µL channels of four sensors each for low-volume parallel measurements, a sealing mechanism that provides appropriate pressure control while assuring liquid confinement and maintaining good stability, and provides a mechanical, electrical, and thermal interface with the characterization electronics. We validate the device by measuring the response of the HFF-QCMD sensors to the air-to-liquid transition, for which the robust Kanazawa–Gordon–Mason theory exists, and then by studying the adsorption of model bioanalytes (neutravidin and biotinylated albumin). With these experiments, we show how the effects of the protein–surface interactions propagate within adsorbed protein multilayers, offering essentially new insight into the design of affinity-based bioanalytical sensors.

A Real-Time Method for Improving Stability of Monolithic Quartz Crystal Microbalance Operating under Harsh Environmental Conditions

“…PBS saline buffer was continuously flown through the reference and sensor channels ( R and S regions, respectively, in Figure S2b in the Supporting Information ), and only NAv and bBSA were injected sequentially in the sensor channel ( S region). Both NAv and bBSA were prepared at high concentration (100 µg/mL) to ensure that adsorption reached saturation, avoiding possible differences among sensors caused by the uneven distribution of the sample in the flow measurement cell [ 33 ]. The response of one pair of resonators ( sensor – reference ) integrated in the MQCM device is depicted in Figure 5 .…”

“…Regarding bBSA injection, although baseline stabilization is not complete because of the temperature influence, we considered that a plateau was reached at 5500 s, where raw Δ f r is −2818 Hz (498 ng/cm 2 ) and Δ D is 52 × 10 −6 . Theoretically, bBSA should be adsorbed over NAv as a monolayer, giving an approximate mass value of 250 ng/cm 2 [ 33 ]. Furthermore, there is a significant mismatch with control experiments shown in Table 1 .…”

“…Label-free detection of protein–ligand interactions is one of the paramount applications of QCM [ 28 ]. In particular, we selected neutravidin (NAv) and biotinylated bovine serum albumin (bBSA) as a relevant model system since these proteins are commonly used in biotechnology and bioanalytics to prepare the sensor surface for further chemical modification [ 29 , 30 , 31 , 32 , 33 ].…”

High Fundamental Frequency (HFF) Monolithic Quartz Crystal Microbalance with Dissipation Array for the Simultaneous Detection of Pesticides and Antibiotics in Complex Food

“…Arrays are based on a 50 MHz one-sided inverted MESA geometry and were optimized in terms of size, electrode geometry and inverted MESA region thickness for spurious mode suppression and operation in liquids [ 30 , 34 ]. Other constraints imposed by the manufacturing and integration with fluidics and electronics [ 39 ] were considered as well.…”

Recent Advancements in Aptamer-Based Surface Plasmon Resonance Biosensing Strategies

“…Conversely, label-free bioanalysis technologies eliminate labeling or tagging procedures, thus allowing the use of natural biomolecules that are suitable for numerous applications in the biomedical field [1][2][3][4]. Various label-free analytical techniques have been reported, involving the use of the quartz crystal microbalance [5], biolayer interferometry [6], surface acoustic waves [7], silicon nanowires [8], and surface plasmon resonance (SPR) [9]. Among them, there has been significant interest in biosensors based on SPR owing to their inherently attractive features, such as rapid detection in real time and the possibility of on-chip integration for smart sensor systems [10][11][12].…”