Quartz Crystal Microbalance Frequency Research Articles

High fundamental frequency QCM humidity sensor based on C60-OH/Ti3C2TX nanocomposite with superior response

The development of high-response quartz crystal microbalance (QCM) humidity sensors typically requires the use of substantial amounts of moisture-sensitive materials, which can lead to slow response and recovery times, as well as inadequate hysteresis performance. In this study, a humidity sensor based on a high fundamental frequency (19.6 MHz) QCM transducer is prepared with fullerenol (C60-OH) nanodot-modified Ti3C2TX as the moisture-sensitive material. With only a tiny amount (1 μg) of material coated, the prepared high-frequency (19.6 MHz) QCM sensor exhibits an unexpectedly strong response to humidity, manifesting a maximum frequency shift up to −12,839 Hz in the range of 2–97 % RH, which is 10 times higher than a low-frequency (10 MHz)-based QCM sensor. Additionally, high-frequency (19.6 MHz) QCM sensor demonstrates excellent sensing performance in low humidity, with a sensitivity of −40.2 Hz/%RH in the range of 0.2–10 % RH. This high response is primarily ascribed to low initial mass of high fundamental frequency QCM and the improvement in moisture-sensing capabilities of Ti3C2TX due to the incorporation of C60-OH. With its outstanding properties, the high-frequency QCM sensor holds great potential for application in human-machine interaction.

Performance evaluation of QCM dew point sensors with different wettability electrode

For accurate identification characteristics of dew point sensors based on quartz crystal microbalance (QCM), the performance of QCM with different wettability electrodes was evaluated. With the materials of 1 H, 1 H, 2 H, 2 H-perfluorodecyltrimethoxysilane (PFOTMS) and 3-(methacryloyloxy) propyltrimethoxysilane (MPTMS), and the cleaning methods of plasma and ultrasound, QCM electrodes with different wettability were prepared. The influence of wettability on dew point identification characteristics was analyzed by observing differences in the static contact angle and surface structure of each QCM, and experiments were carried out to study the frequency characteristics of each QCM. The results demonstrated that when the wettability of the QCM electrodes was lower, the dew was close to spherical and its distribution was dense, which was beneficial for accurate identification. The dew point temperature was identified by detecting the temperature of the point when the QCM frequency variation slop changed to 0, and the QCM treated with plasma-PFOTMS had excellent measurement performance as its maximum measurement error was less than 0.38 ℃DP at the dew point range of 0–14 ℃DP in five days. This study provided a new approach for optimizing high-precision QCM dew point sensors.

Determination of Menthol by a Quartz Crystal Microbalance (QCM) Using Gold Nanoparticle Amplification

Menthol is a monocyclic monoterpene with a distinct flavor that is frequently utilized in a variety of food and medicinal items. In this study, a sensitive method based on quartz crystal microbalance (QCM) with gold nanoparticles amplification was developed. A gold chip was initially modified with mono(6-mercapto-6-deoxy)-β-cyclodextrin (SH-β-CD) through Au-S affinity binding. When menthol is absent, the host–guest interaction brings ferrocene (Fc) labeled-ssDNA (Fc-ssDNA) to enter the SH-β-CD cavity. The hybridization between Au nanoparticles functionalized-ssDNA (AuNPs-ssDNA) and Fc-ssDNA produces a significant frequency shift. However, in the presence of menthol, the inclusion competition between Fc and menthol reduces AuNPs-ssDNA modification on the chip surface. In this case, the change of QCM frequency is greatly reduced by menthol. Thus, menthol determination is accomplished by measuring the change in QCM frequency with a linear range from 10−8 M to 10−2 M and a limit of detection of 7.81 nM, which is superior to previously reported results. The method has also been applied in real samples such as mint and essential oil with satisfactory results.

MOF-composite sensors to eliminate the QCM positive frequency shift

In a quartz crystal microbalance (QCM) Sauerbrey equation can usually be applied in the ideal scenario and when the QCM frequency shift goes to the negative direction. In some cases, however, the requirements to achieve the ideal condition are not fulfilled and thus leading to QCM positive frequency shift phenomenon. Herein we have also observed that a porphyrin-based metal organic frameworks (MOF), namely MOF-525(Zn), QCM sensor also exhibits the positive frequency shift phenomenon when exposed to xylene isomers, which could be caused by the loose attachment of the MOF nanoparticles on the QCM surface. Therefore, in the presence of the analytes, the bonding between the MOF and the QCM surface is disturbed and higher analyte concentration also leads to the increase of the sensitive layer stiffness, resulting in higher positive frequency shift. However, such a phenomenon can be completely eliminated by simply adding polymer to MOF nanoparticle sensors to strengthen the bonding of MOF nanoparticles to the QCM surface. Through this study we have shown that adjusting the amount of polymer is very crucial to completely reverse the positive frequency response. Otherwise, it appears a critical analyte concentration of gas analytes where the QCM frequency shift changes its direction from negative to positive response. Lastly, the same strategy has also been used to other MOF-based QCM sensor systems where their sensitive layer is built from other MOFs, namely MOF-525 and NU-902, and ethanol is used as the analyte to prove the generalizability of this simple approach.

Accurate Multi-Channel QCM Sensor Measurement Enabled by FPGA-Based Embedded System Using GPS

This paper presents a design and implementation proposal for a real-time frequency measurement system for high-precision, multi-channel quartz crystal microbalance (QCM) sensors using a field programmable gate array (FPGA). The key contribution of this work lies in the integration of a frequency measurement and mass resolution computation based on Global Positioning System (GPS) signals within a single FPGA chip, utilizing Input/Output Blocks to incorporate logic QCM oscillator circuits. The FPGA design enables parallel processing, ensuring accurate measurements, faster calculations, and reduced hardware complexity by minimizing the need for external components. As a result, a cost-effective and accurate multi-channel sensor system is developed, serving as a reconfigurable standalone measurement platform with communication capabilities. The system is implemented and tested using the FPGA Xilinx Virtex-6, along with multiple QCM sensors. The implementation on a Xilinx XC6VLX240T FPGA achieves a maximum frequency of 324 MHz and consumes a dynamic power of 120 mW. Notably, the design utilizes a modest number of resources, requiring only 188 slices, 733 flip-flops, and 13 IOBs to perform a double-channel sensor microbalance. The proposed system meets the precision measurement requirements for QCM sensor applications, exhibiting low measurement error when monitoring QCM frequencies ranging from 1 to 50 MHz, with an accuracy of 0.2 ppm and less than 0.1 Hz.

Interaction of negatively and positively capped gold nanoparticle with different lipid model membranes

The use of functionalised gold nanoparticles in biomedical applications is expanding. Here we explore the interaction of gold nanoparticles with lipid membranes using readily available equipment and basic techniques to explore how the charge on the nanoparticles, and the nature of the lipid, influences the interaction. Gold nanoparticles were synthesised with two different surface functionalisations, negatively charged citrate groups and positively charged cetyltrimethylammonium groups from CTAB, to determine how surface charge affects the interaction of the nanoparticles with the Zwitterionic lipid POPC and the anionic lipid POPG. It was observed that the surface pressure/area isotherms of POPG monolayers on exposure to citrate capped nanoparticles were not shifted to higher molecular areas as much as those of POPC, suggesting that the anionic headgroups of the POPG lipid repel the anionic surface charge of the citrate capped nanoparticles to some extent limiting inclusion. In contrast, the surface pressure/area isotherms of the POPG monolayers exposed to CTAB capped nanoparticles are shifted to higher molecular areas more than for the POPC monolayers. The interaction of anionic nanoparticles with lipid bilayers was measured by the mass change of the bilayer deposited on the surface of a quartz crystal microbalance (QCM) exposed to nanoparticles in an aqueous phase flow. The QCM frequency changes show that bilayers of unsaturated phosophocholine lipids readily took up particles, whereas for the saturated lipid DPPC significant uptake was only observed when the bilayer was warmed to above its gel-to-fluid transition temperature, Tm. This is possibly due to an increase in the molecular mobility and bilayer bending modulus, κ, of the bilayer.

Parameters controlling octadecyl phosphonic acid self-assembled monolayers on titanium dioxide for anti-fouling biomedical applications

Octadecylphosphonic acid (ODPA) self-assembled monolayers (SAMs) have demonstrated potential for deterring bacterial attachment to titanium, however the coating process is time consuming and uses toxic solvents. In this study, ODPA SAM quantity, quality, and structure were evaluated on titanium quartz crystal microbalance (QCM) sensors by varying solvent type (anisole or cyclopentyl methyl ether (CPME), environmentally friendly non-polar solvents); ODPA concentration (0.5 mM or 1 mM); and temperature (21 °C or 60 °C). Surfaces were characterised using QCM frequency and dissipation measurements and Sauerbrey mass calculations; X-ray photoelectron spectroscopy; water contact angle measurements; and temperature-programmed desorption mass spectrometry (TPD-MS). Anti-fouling ability was established against Staphylococcus aureus. Incubation in 0.5 mM ODPA in CPME at 21 °C rapidly formed uniform rigid ODPA SAMs as demonstrated by high Sauerbrey mass (≈285-290 ng/cm2), viscoelastic modelling, high atomic percentage surface phosphorus (1.1%) and high water contact angles (117.6 ± 2.5°), consistent across the entire sample surface. High temperatures or the use of anisole resulted in suspected multilayer formation, which reduced bacterial attachment. TPD-MS confirmed covalent bonding of ODPA SAMs on TiO2 at ≈ 110–120 °C and thermal stability below 300 °C. This study demonstrates the key parameters that control ODPA SAM formation on titanium and their future potential for biomedical applications.

A versatile gas transmission device with precise humidity control for QCM humidity sensor characterizations

Previously, several high-sensitivity and inexpensive humidity sensors with rapid response times have been reported. However, obtaining reliable humidity characteristics of highly sensitive devices, such as quartz crystal microbalance (QCM) sensors, requires the development of new, affordable gas transmission setups. With that in mind, we developed a novel, comprehensive gas transmission system that combined elements from two commonly used systems (saturated salts and gas mixing), which facilitated automatic gas humidity changes, reliable gas flows in closed measurement chambers, and limited the influence of the external atmosphere/pollutants. The gas transmission device performance was tested using a commercial digital hygrometer and highly sensitive QCM coated with graphene oxide for six different humidity sets in range 5.3–82.6% RH. The dynamic repeatability tests proved the superb stability of the system, as QCM frequency deviation did not exceed 2% of frequency shifts among ten switching cycles (one hour each). Therefore, this system allowed a thorough investigation of humidity sensors properties in a controlled environment with a high precision.

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

As in the case of the food industry in general, there is a global concern about safety and quality in complex food matrices, such as honey, which is driving the demand for fast, sensitive and affordable analytical techniques across the honey-packaging industry. Although excellent techniques such as liquid chromatography-tandem mass spectrometry (LC-MS/MS) are available, these are located in centralized laboratories and are still lacking in speed, simplicity and cost-effectiveness. Here, a new approach is presented where a competitive immunoassay is combined with a novel High Fundamental Frequency Quartz Crystal Microbalance with Dissipation (HFF-QCMD) array biosensor for the simultaneous detection of antibiotics and pesticides in honey. Concretely, thiabendazole and sulfathiazole residues were monitored in spiked honey samples. Results revealed that HFF-QCMD arrays provide a complementary and reliable tool to LC-MS/MS for the analysis of contaminants in these kinds of complex matrices, while avoiding elaborate sample pre-treatment. The good sensitivity achieved (I50 values in the 70–720 µg/kg range) and the short analysis time (60 min for 24 individual assays), together with the ability for multiple analyte detection (24 sensor array) and its cost-effectiveness, pave the way for the implementation of a fast on-line, in situ routine control of potentially hazardous chemical residues in honey.

Detection of globular and fibrillar proteins by quartz crystal microbalance sensor coated with a functionalized diamond thin film

This study presents a sensor based on quartz crystal microbalance (QCM) coated with nanocrystalline diamond (NCD) thin film, functionalization method and novel application of such sensor. Diamond-coated QCMs (DQCMs) were superficially terminated by hydrogen and oxygen (H-NCD and O-NCD) to control its surface dipole/potential. Two protein solutions were tested: bovine serum albumin (BSA) and fibronectin (FN). We performed reference measurements of serial resonant frequency (SRF) of clean QCMs loaded with protein and compared them with SRF shifts DQCMs loaded with proteins. In order to investigate the influence of the deposited NCD thin film on QCM measuring capabilities, additional FEM analysis was performed. The simulation results showed that QCM sensors maintain the sensing capabilities with a rigid thin film of NCD on its surface. The shift of SRF was demonstrably caused by the weight of protein adhered to the diamond film's surface. We compared masses estimated from the Sauerbrey equation to characterize the adhesive properties of the studied proteins. Comparing bare QCM and DQCM, we discovered diamonds enhance the sensing performance for proteins. At the same time, it saturates quickly with phosphate buffer saline used as a diluent solution for proteins. Results showed a significant increase in protein adhesion confirmed by the increase of the mass for both oxygen and hydrogen-terminated DQCMs. Moreover, a different time-dependent behaviour (i.e. different adsorption rate, degrees of physisorption and/or preference of the diamond surface functionalization) of the O-NCD and H-NCD QCMs was observed for BSA and FN proteins. In this meaning, we propose aschematic model which describes the detection principle of BSA and FN proteins on H- and O-terminated DQCM sensors. Finally, a simple proof of concept for using the functionalized diamond-coated sensors with current stimulation and EQCM (Electrochemical Quartz Crystal Microbalance) is also proposed.

Acoustic Array Biochip Combined with Allele-Specific PCR for Multiple Cancer Mutation Analysis in Tissue and Liquid Biopsy.

Regular screening of point mutations is of importance to cancer management and treatment selection. Although techniques like next-generation sequencing and digital polymerase chain reaction (PCR) are available, these are lacking in speed, simplicity, and cost-effectiveness. The development of alternative methods that can detect the extremely low concentrations of the target mutation in a fast and cost-effective way presents an analytical and technological challenge. Here, an approach is presented where for the first time an allele-specific PCR (AS-PCR) is combined with a newly developed high fundamental frequency quartz crystal microbalance array as biosensor for the amplification and detection, respectively, of cancer point mutations. Increased sensitivity, compared to fluorescence detection of the AS-PCR amplicons, is achieved through energy dissipation measurement of acoustically "lossy" liposomes binding to surface-anchored dsDNA targets. The method, applied to the screening of BRAF V600E and KRAS G12D mutations in spiked-in samples, was shown to be able to detect 1 mutant copy of genomic DNA in an excess of 104 wild-type molecules, that is, with a mutant allele frequency (MAF) of 0.01%. Moreover, validation of tissue and plasma samples obtained from melanoma, colorectal, and lung cancer patients showed excellent agreement with Sanger sequencing and ddPCR; remarkably, the efficiency of this AS-PCR/acoustic methodology to detect mutations in real samples was demonstrated to be below 1% MAF. The combined high sensitivity and technology-readiness level of the methodology, together with the ability for multiple sample analysis (24 array biochip), cost-effectiveness, and compatibility with routine workflow, make this approach a promising tool for implementation in clinical oncology labs for tissue and liquid biopsy.

Schottky-type GaN-based UV photodetector with atomic-layer-deposited TiN thin film as electrodes.

In this work, a GaN-based UV photodetector with an asymmetric electrode structure was fabricated by atomic layer deposition (ALD) of TiN layers. The thickness of the TiN can be monitored in situ by a quartz crystal microbalance (QCM) and precisely controlled through the modulation of deposition cycles. During the ALD process, periodic variation in the QCM frequency was observed and correlated to the physical adsorption, chemical bonding, and the excessive precursor exhaust, which included tetrakis(dimethylamino)titanium (TDMAT) and N sources. The asymmetric TiN/GaN/TiN photodetector showed excellent photosensing performance, with a UV-visible rejection ratio of 173, a responsivity of 4.25 A/W, a detectivity of 1.1×1013 Jones, and fast response speeds (a rise time of 69 μs and a decay time of 560 μs). Moreover, the device exhibits high stability, with an attenuation of only approximately 0.5% after 360 nm light irradiation for 157 min. This result indicates the potential of TiN as a transparent contact electrode for GaN-based optoelectronic devices.

Determination of Resonance Parameters of The PANI Thin Film Fabricated using Spin Coating Method

This study aims to determine the resonance parameters of polyaniline thin films to better understand the viscoelasticity properties of polyaniline films. The spin coating method was used with varying solvent concentrations and rotating speed of spin coater during the deposition Polyaniline (PANI) thin film on a quartz crystal microbalance (QCM). To determine the resonance parameters of the PANI thin film, the impedance and QCM frequency measurements were first carried out before and after coated with PANI. The modelling used is a modified BVD model, and the determined resonance parameters are C0, C1, L1, R1, L2 and R2. From the results of the analysis using the GRG Nonlinear solver program, it was found that solution concentration and rotational speed in the spin coating process has a significant effect on resonator parameters of PANI thin film. The best solution concentration from this study was 2% DMF with a rotational speed of 2,000 rpm. This is because in these conditions it provides a minimal damping effect on QCM.

Label-free characterization of an extracellular vesicle-based therapeutic.

Interest in mesenchymal stem cell derived extracellular vesicles (MSC‐EVs) as therapeutic agents has dramatically increased over the last decade. Current approaches to the characterization and quality control of EV‐based therapeutics include particle tracking techniques, Western blotting, and advanced cytometry, but standardized methods are lacking. In this study, we established and verified quartz crystal microbalance (QCM) as highly sensitive label‐free immunosensing technique for characterizing clinically approved umbilical cord MSC‐EVs enriched by tangential flow filtration and ultracentrifugation. Using QCM in conjunction with common characterization methods, we were able to specifically detect EVs via EV (CD9, CD63, CD81) and MSC (CD44, CD49e, CD73) markers. Furthermore, analysis of QCM dissipation versus frequency allowed us to quantitatively determine the ratio of marker‐specific EVs versus non‐vesicular particles (NVPs) – a parameter that cannot be obtained by any other technique so far. Additionally, we characterized the topography and elasticity of these EVs by atomic force microscopy (AFM), enabling us to distinguish between EVs and NVPs in our EV preparations. This measurement modality makes it possible to identify EV sub‐fractions, discriminate between EVs and NVPs, and to characterize EV surface proteins, all with minimal sample preparation and using label‐free measurement devices with low barriers of entry for labs looking to widen their spectrum of characterization techniques. Our combination of QCM with impedance measurement (QCM‐I) and AFM measurements provides a robust multi‐marker approach to the characterization of clinically approved EV therapeutics and opens the door to improved quality control.

Interpretation of Quartz Crystal Microbalance Behavior with Viscous Film Using a Mason Equivalent Circuit

In odor sensing based on Quartz Crystal Microbalances (QCMs), the sensing film is crucial for both sensor sensitivity and selectivity. The typical response of the QCM due to sorption is a negative frequency shift. However, in some cases, the sorption causes a positive frequency shift, and then, Sauerbrey’s equation and Kanazawa’s equation cannot be applied to this situation. We model the QCM response with a Mason equivalent circuit. The model approximates a single layer of a uniform viscous coating on the QCM. The simulation of the equation circuit shows the possibility of the positive frequency change when the sorption occurs, which is the situation we find in some of the odor sensing applications. We measured the QCM frequency and resistance using the Vector Network Analyzer (VNWA). The QCMs were coated with glycerol, PEG2000, and PEG20M. To simulate odor exposure, a microdispenser was used to deposit the water. A positive frequency shift was observed in the case of PEG2000, and a negative frequency change was obtained for PEG20M. These results can be explained by the Mason equivalent circuit, with the assumption that when the film is exposed to water, its thickness increases and its viscosity decreases.

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

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.

Topology Challenge for the Assessment of Living Cell Deposits with Shear Bulk Acoustic Biosensor.

Shear bulk acoustic type of resonant biosensors, such as the quartz crystal microbalance (QCM), give access to label-free in-liquid analysis of surface interactions. The general understanding of the sensing principles was inherited from past developments in biofilms measurements and applied to cells while keeping the same basic assumptions. Thus, the biosensor readouts are still quite often described using ‘mass’ related terminology. This contribution aims to show that assessment of cell deposits with acoustic biosensors requires a deep understanding of the sensor transduction mechanism. More specifically, the cell deposits should be considered as a structured viscoelastic load and the sensor response depends on both material and topological parameters of the deposits. This shifts the paradigm of acoustic biosensor away from the classical mass loading perspective. As a proof of the concept, we recorded QCM frequency shifts caused by blood platelet deposits on a collagen surface under different rheological conditions and observed the final deposit shape with atomic force microscopy (AFM). The results vividly demonstrate that the frequency shift is highly impacted by the platelet topology on the bio-interface. We support our findings with numerical simulations of viscoelastic unstructured and structured loads in liquid. Both experimental and theoretical studies underline the complexity behind the frequency shift interpretation when acoustic biosensing is used with cell deposits.

Investigating Adsorbing Viscoelastic Fluids Using the Quartz Crystal Microbalance.

There is little research on using the quartz crystal microbalance (QCM) with adsorbing viscoelastic fluids. These fluids are widely encountered but often difficult to study as many are opaque and highly viscous. Since the QCM does not involve any scattering or reflection of input radiation, it has the potential to study these complex fluids to determine the relative viscoelasticity of the bulk fluid and surface adsorption of active species onto different substrates. In the current study, both Newtonian (sucrose) and viscoelastic (sodium polystyrene sulfonate (NaPSS)) fluids were introduced into the QCM, and the sensor responses were compared. QCM responses of Newtonian sucrose solutions matched the Kanazawa and Gordon model (KG model), as expected. The QCM responses with viscoelastic NaPSS solutions were well below those described by the KG model. A viscoelastic model was used to determine the fluid viscosity and shear modulus at a very high frequency. It was found that the viscosity of NaPSS did not change much compared with low-frequency rheometer measurements, but a significant increase in the shear modulus of several orders of magnitude was found at the QCM frequencies. Modifying the KG model frequency shifts by multiplying by the QCM shear wave decay length ratio, X = δV/δN, we were able to match the measured QCM values in viscoelastic NaPSS solutions. The QCM dissipation values for NaPSS were matched in a similar way by multiplying the KG model by X1/3. By changing the QCM sensor from silica (no NaPSS adsorption) to alumina (NaPSS adsorption), it was shown that the adsorption isotherm of NaPSS on alumina could be recovered and fitted with a Langmuir isotherm despite the frequency response being only a small fraction of the total measured QCM signal.

Swelling Effect Observation of The Copper Phthalocyanine Layer on QCM and Its Effect on Surface Roughness and Morphology Changes

Copper Phthalocyanine (CuPc) is one material often used for the active layer on Quartz Crystal Microbalance (QCM) sensor. One important mechanism which can shorten the recovery time in the sensor is the swelling effect. The swelling effect is studied by observing the morphology of the layer and subsequent changes in QCM frequency during surface contact with three kinds of solution. The solutions used in this study were distilled water, phosphate-buffered saline (PBS) and Tris-HCl. The results of frequency measurements indicate a swelling effect which was shown by the decrease of the frequency change after the injection process. The most significant change in frequency occurs in PBS solutions. This change occurs as PBS has a higher molecular weight and ionic strength than distilled water and Tris-HCl. SEM results show that the swelling of the CuPc layer changes the microstructure layer. A decrease in the roughness of the CuPc layer was also observed due to the presence of buffer solution molecules that diffuse through the layer. Upon diffusion of the solution molecules into the CuPc layer, a continuous decrease in the QCM frequency occurs. Further, the diffusion caused the CuPc microstructure to become more tenuous.

High Fundamental Frequency Quartz Crystal Microbalance (HFF-QCMD) Immunosensor for detection of sulfathiazole in honey

In this study, a piezoelectric immunosensor based on High Fundamental Frequency Quartz Crystal Microbalance (HFF-QCMD) technology was developed for detection of sulfathiazole in honey. The biorecognition was based on a competitive immunoassay in the conjugate-coated format, using monoclonal antibodies as specific immunoreagents. The quantification of sulfathiazole was performed by building the corresponding calibration standard curve in diluted honey (1/140). Due to the competitive nature of the immunoassay, the standard curve showed a sigmoidal pattern with limits of detection (LOD) and quantification (LOQ) of 0.10 μg/kg and 2 μg/kg honey, respectively. The LOD reached by this immunosensor is 40–50 times lower than those reported by other techniques for antibiotic detection. Moreover, this method requires minimum honey pre-treatment, making it faster and simpler than other methods. This immunosensor meets the precision and accuracy requirements established by SANCO guidelines, when sulfathiazole concentration in honey is not lower than 10 μg/kg. These findings could be the basis for reaching enough reliability for lower concentrations. Therefore, HFF-QCMD immunosensors can be considered a feasible alternative to current techniques for rapid and highly sensitive determination of sulfathiazole in honey with minimum sample preparation.