Multi-channel Microfluidic Chip Research Articles

Microfluidic wet spinning of antibacterial collagen composite fibers supported by chelate effect of tannic acid with silver ions

In this work, we reported the preparation of a novel type of collagen composite fiber with antibacterial properties by utilizing the hydrodynamic focusing effect of the multichannel microfluidic chip and microfluidic wet spinning technology (MWST). Specifically, tannin (TA)-grafted collagen solution was used as the precursor, ethanol anhydrous was used as the sheath flow, and AgNO3 solution was used as the spacer flow between the precursor and the sheath flow. The morphologies, structures, and properties of obtained collagen composite fibers were seriously analyzed. These results indicated that TA can not only form strong crosslinking networks of hydrogen bonds with collagen fibrils, but also chelate with Ag+, thus resulting in a synergistic enhancement of the mechanical properties, thermal stability, and antibacterial properties of collagen/TA-Ag composite fibers. These collagen composite fibers with excellent mechanical properties and antibacterial properties might have potential applications in the surgical suture field.

Study on Microfluidic Chip Flow Rate Uniformity for Cell Activity Detection.

During the cell viability detection process inside a microfluidic chip, the more uniform the distribution of medium flow rates, the higher the accuracy of detection results. In order to achieve this goal, a multichannel microfluidic chip with uniform distribution of medium flow rates has been successfully designed. The multichannel microfluidic chip is designed with cell injection channels, vascular network-shaped medium injection channels, buffer zones, and a culture chamber. The medium flow rates inside culture chambers of the multichannel microfluidic chip and the common single-channel microfluidic chip are compared by COMSOL Multiphysics software and particle velocimetry experiment. The simulation and experimental results show that the medium flow rate distribution inside the culture chamber of the multichannel microfluidic chip is more uniform and changes more smoothly. When the medium perfusion flow rate is 0.5 μL/min, the maximum flow rate difference inside the culture chamber of the single-channel microfluidic chip is more than 13 times that of the multichannel microfluidic chip. Therefore, the multichannel microfluidic chip can ensure a uniform supply of medium inside the culture chamber, which is beneficial to improve the accuracy of cell viability detection.

Cell Membranes from Tumor-Tropic MSCs Screened by a Microfluidic Chip for Drug Nanoparticles Encapsulation and Cancer Targeted Therapy.

Nanoparticles (NPs)-based drug carriers are effective in reducing systemic toxicity and drug resistance for chemotherapy, and an emerging trend focuses on integrating cell membranes with nanomedicines for tumor targeting. Mesenchymal stem cells (MSCs) are promising candidates due to their unique tropism toward cancer cells, yet the tumor-tropic abilities can differ for MSCs sourced from different tissues. Here, a multichannel microfluidic chip to screen different sourced MSCs with the greatest tropism toward cervical cancer cells is developed. Based on this, the cell membranes from the chorionic plate-derived MSC are isolated and membrane-camouflaged platinum prodrug composite NPs for cervical cancer treatment are prepared. Results demonstrate that the composite NPs can effectively target tumor sites and have a therapeutic effect both in vitro and in vivo. It is believed that the present microfluidic platform is a powerful tool for cell screening and tumor-on-a-chip studies, and the derived nanodelivery system represents the great value of cell membrane-camouflaged nanomedicine for targeted cancer therapy.

Design, simulation and application of multichannel microfluidic chip for cell migration

Cell migration is defined as the directional movement of cells toward a specific chemical concentration gradient, which plays a crucial role in embryo development, wound healing and tumor metastasis. However, current research methods showed low flux and are only suitable for single-factor assessment, and it was difficult to comprehensively consider the effects of other parameters such as different concentration gradients on cell migration behavior. In this paper, a four-channel microfluidic chip was designed. Its characteristics were as follows: it relied on laminar flow and diffusion mechanisms to establish and maintain a concentration gradient; it was suitable for observation of cell migration in different concentration gradient environment under a single microscope field; four cell isolation zones (20 μm width) were integrated into the microfluidic device to calibrate the initial cell position, which ensured the accuracy of the experimental results. In particular, we used COMSOL Multiphysics software to simulate the structure of the chip, which demonstrated the necessity of designing S-shaped microchannel and horizontal pressure balance channel to maintain concentration gradient. Finally, neutrophils were incubated with advanced glycation end products (AGEs, 0, 0.2, 0.5, 1.0 μmol·L -1), which were closely related to diabetes mellitus and its complications. The migration behavior of incubated neutrophils was studied in the 100 nmol·L -1 of chemokine (N-formylmethionyl-leucyl-phenyl-alanine) concentration gradient. The results prove the reliability and practicability of the microfluidic chip.

Light sheet based volume flow cytometry (VFC) for rapid volume reconstruction and parameter estimation on the go

Optical imaging is paramount for disease diagnosis and to access its progression over time. The proposed optical flow imaging (VFC/iLIFE) is a powerful technique that adds new capabilities (3D volume visualization, organelle-level resolution, and multi-organelle screening) to the existing system. Unlike state-of-the-art point-illumination-based biomedical imaging techniques, the sheet-based VFC technique is capable of single-shot sectional visualization, high throughput interrogation, real-time parameter estimation, and instant volume reconstruction with organelle-level resolution of live specimens. The specimen flow system was realized on a multichannel (Y-type) microfluidic chip that enables visualization of organelle distribution in several cells in-parallel at a relatively high flow-rate (2000 nl/min). The calibration of VFC system requires the study of point emitters (fluorescent beads) at physiologically relevant flow-rates (500–2000 nl/min) for determining flow-induced optical aberration in the system point spread function (PSF). Subsequently, the recorded raw images and volumes were computationally deconvolved with flow-variant PSF to reconstruct the cell volume. High throughput investigation of the mitochondrial network in HeLa cancer cell was carried out at sub-cellular resolution in real-time and critical parameters (mitochondria count and size distribution, morphology, entropy, and cell strain statistics) were determined on-the-go. These parameters determine the physiological state of cells, and the changes over-time, revealing the metastatic progression of diseases. Overall, the developed VFC system enables real-time monitoring of sub-cellular organelle organization at a high-throughput with high-content capacity.

All-fiber biological detection microfluidic chip based on space division and wavelength division multiplexing technologies.

To further reduce the size of a microfluidic detection chip and the sample consumption and to shorten the chip manufacturing cycle, an all-fiber SPR detection multichannel microfluidic chip was proposed and demonstrated in this paper. The microfluidic channel of the proposed chip was provided by the air channel of a double side-hole fiber, the detection unit was fabricated using a dumbbell fiber with a fiber core exposed to air, and the sensing probe was composed and packaged by fiber micro-processing technology. The internal double channels of the fiber constructed from double side-hole and dumbbell fibers can realize dual channel detection based on space division multiplexing. 30 nm silver and 50 nm gold films were respectively coated on the left and right sides of the dumbbell fiber, which can realize the dual channel simultaneous detection based on wavelength division multiplexing. We employed the proposed microfluidic chip to detect immunoglobulin G and dopamine molecules, where the average sensitivity is 0.252 nm (mg mL-1)-1 and 0.061 nm (μg mL-1)-1, and the LOD is 0.397 mg mL-1 and 1.639 μg mL-1, respectively. The microfluidic channel and detection unit of all-fiber multi-channel SPR detection microfluidic chip are provided by a soft and flexible fiber, which is compact in structure, flexible in fabrication and short in manufacturing cycle, making it possible for the microfluidic chip to enter the human body for detection and enabling a new approach for the fabrication of wearable detection microfluidic devices. This provides a new idea for the development of microfluidic chips.

In Situ Pinpoint Photopolymerization of Phos-Tag Polyacrylamide Gel in Poly(dimethylsiloxane)/Glass Microchip for Specific Entrapment, Derivatization, and Separation of Phosphorylated Compounds.

An improved method for the online preconcentration, derivatization, and separation of phosphorylated compounds was developed based on the affinity of a Phos-tag acrylamide gel formed at the intersection of a polydimethylsiloxane/glass multichannel microfluidic chip toward these compounds. The acrylamide solution comprised Phos-tag acrylamide, acrylamide, and N,N-methylene-bis-acrylamide, while 2,2′-azobis[2-methyl-N-(2-hydroxyethyl)propionamide] was used as a photocatalytic initiator. The Phos-tag acrylamide gel was formed around the channel crossing point via irradiation with a 365 nm LED laser. The phosphorylated peptides were specifically concentrated in the Phos-tag acrylamide gel by applying a voltage across the gel plug. After entrapment of the phosphorylated compounds in the Phos-tag acrylamide gel, 5-(4,6-dichlorotriazinyl)aminofluorescein (DTAF) was introduced to the gel for online derivatization of the concentrated phosphorylated compounds. The online derivatized DTAF-labeled phosphorylated compounds were eluted by delivering a complex of phosphate ions and ethylenediamine tetraacetic acid as the separation buffer. This method enabled sensitive analysis of the phosphorylated peptides.

A conjoint multi metal-ion iminodiacetic acid monolith microfluidic chip for structural-based protein pre-fractionation.

PDMS-based multichannel microfluidic chip was designed and fabricated in a simple approach using readily available tools. UV-initiated in situ polymerization of poly(2-hydroxy ethyl methacrylate-co-di(ethylene glycol) diacrylate-co-N,N'-diallyl l-tartardiamide) in an Eppendorf tube was achieved within 40min. This polymerization process was successfully translated to a microfluidic chip format without any further modifications. Iminodiacetic acid was successfully immobilized on aldehyde functional monoliths via Schiff base reaction and confirmed by FT-IR spectroscopy. Four transition metal ions (Co (II), Zn (II), Ni (II), and Cu (II)) were chelated individually on four IDA-monolith microfluidic chips. The conjoint metal-ion monolith microfluidic chip has displayed high permeability (9.40× 10-13 m2 ) and a porosity of 32.8%. This affinity microfluidic chip has pre-fractioned four human plasma proteins (fibrinogen, immunoglobulin, transferrin, and human serum albumin) based on their surface-exposed histidine surface topography. A protein recovery of approximately 95% (Bradford assay data) was achieved. The multimonolith microchip can be reusable even after three protein adsorption-desorption cycles.

Intestinal Models for Personalized Medicine: from Conventional Models to Microfluidic Primary Intestine-on-a-chip.

Intestinal dysfunction is frequently driven by abnormalities of specific genes, microbiota, or microenvironmental factors, which usually differ across individuals, as do intestinal physiology and pathology. Therefore, it’s necessary to develop personalized therapeutic strategies, which are currently limited by the lack of a simulated intestine model. The mature human intestinal mucosa is covered by a single layer of columnar epithelial cells that are derived from intestinal stem cells (ISCs). The complexity of the organ dramatically increases the difficulty of faithfully mimicking in vivo microenvironments. However, a simulated intestine model will serve as an indispensable foundation for personalized drug screening. In this article, we review the advantages and disadvantages of conventional 2-dimensional models, intestinal organoid models, and current microfluidic intestine-on-a-chip (IOAC) models. The main technological strategies are summarized, and an advanced microfluidic primary IOAC model is proposed for personalized intestinal medicine. In this model, primary ISCs and the microbiome are isolated from individuals and co-cultured in a multi-channel microfluidic chip to establish a microengineered intestine device. The device can faithfully simulate in vivo fluidic flow, peristalsis-like motions, host-microbe crosstalk, and multi-cell type interactions. Moreover, the ISCs can be genetically edited before seeding, and monitoring sensors and post-analysis abilities can also be incorporated into the device to achieve high-throughput and rapid pharmaceutical studies. We also discuss the potential future applications and challenges of the microfluidic platform. The development of cell biology, biomaterials, and tissue engineering will drive the advancement of the simulated intestine, making a significant contribution to personalized medicine in the future. Graphical abstractThe intestine is a primary organ for digestion, absorption, and metabolism, as well as a major site for the host-commensal microbiota interaction and mucosal immunity. The complexity of the organ dramatically increases the difficulty of faithfully mimicking in vivo microenvironments, though physiological 3-dimensional of the native small intestinal epithelial tissue has been well documented. An intestinal stem cells-based microfluidic intestine-on-a-chip model that faithfully simulate in vivo fluidic flow, peristalsis-like motions, host-microbe crosstalk, and multi-cell type interactions will make a significant contribution.

Electronic Blood Vessel

Summary Advances in bioelectronics have great potential to address unsolved biomedical problems in the cardiovascular system. By using poly(L-lactide-co-ϵ-caprolactone), which encapsulates liquid metal to make flexible and biodegradable electrical circuitry, we develop an electronic blood vessel that can integrate flexible electronics with three layers of blood-vessel cells, to mimic and go beyond the natural blood vessel. It can improve the endothelialization process through electrical stimulation and can enable controlled gene delivery into specific parts of the blood vessel via electroporation. The electronic blood vessel has excellent biocompatibility in the vascular system and shows great patency 3 months post-implantation in a rabbit model. The electronic blood vessel would be an ideal platform to enable diagnostics and treatments in the cardiovascular system and can greatly empower personalized medicine by creating a direct link of the vascular tissue-machine interface.

A microfluidic approach for synchronous and nondestructive study of the permeability of multiple oocytes

Investigation of oocyte membrane permeability plays a crucial role in fertility preservation, reproductive medicine, and reproductive pharmacology. However, the commonly used methods have disadvantages such as high time consumption, low efficiency, and cumbersome data processing. In addition, the developmental potential of oocytes after measurement has not been fully validated in previous studies. Moreover, oocytes can only maintain their best status in vitro within a very limited time. To address these limitations, we developed a novel multichannel microfluidic chip with newly designed micropillars that provide feasible and repeatable oocyte capture. The osmotic responses of three oocytes at different or the same cryoprotectant (CPA) concentrations were measured simultaneously, which greatly improved the measurement efficiency. Importantly, the CPA concentration dependence of mouse oocyte membrane permeability was found. Moreover, a neural network algorithm was employed to improve the efficiency and accuracy of data processing. Furthermore, analysis of fertilization and embryo transfer after perfusion indicated that the microfluidic approach does not damage the developmental potential of oocytes. In brief, we report a new method based on a multichannel microfluidic chip that enables synchronous and nondestructive measurement of the permeability of multiple oocytes.

Multi-channel surface plasmon resonance biosensor using prism-based wavelength interrogation.

A portable multi-channel surface plasmon resonance (SPR) biosensor device using prism-based wavelength interrogation is presented. LEDs were adopted as a simple and inexpensive light source, providing a stable spectrum bandwidth for the SPR system. The parallel light was obtained by a collimated unit and illuminated on the sensing chip at a specific angle. A simple, compact and cost-effective spectrometer part constituted of a series of lenses and a prism was designed for the collection of reflected light. Using the multi-channel microfluidic chip as the sensing component, spectral images of multiple tests could be acquired simultaneously, improving the signal processing and detection throughput. Different concentrations of sodium chloride aqueous solution were used to calibrate the device. The linear detection range was 4.32 × 10-2 refractive index units (RIU) and the limit of detection was 6.38 × 10-5 RIU. Finally, the performance of the miniaturized SPR system was evaluated by the detection of immunoglobulin G (IgG).

Precise evaluation of liquid conductivity using a multi-channel microfluidic chip and direct-current resistance measurements

In various research fields related to electrochemistry, such as biosensors and energy storage engineering, the conductivity of an electrolyte solution is one of the most fundamental parameters that determines device design and performance. The simplest procedure for obtaining the conductivity of a liquid is to (i) measure the direct-current resistance of liquid whose volume and dimensions is well-defined and (ii) calculate the conductivity from the measured resistance. However, this method has not been widely used because the measured resistance always includes electrode-electrolyte interface resistance and the extraction of a correct conductivity is difficult. In this study, we designed a multi-channel microfluidic chip that can remove the effects of interface resistance in determining the intrinsic resistance of a liquid and developed a method for the precise evaluation of liquid conductivity. We observed that the interface resistance was significantly affected by the channel length and applied voltage. We measured the intrinsic resistance of phosphate-buffered saline (PBS), conductivity standard solutions, and cell culture media using the proposed multi-channel chip including different-length channels, and we removed the effect of voltage-dependent interface resistance by applying a constant current source for the measurement and determined the precise conductivities of these solutions. We verified the accuracy of the proposed method by comparing the results with the conductivity measured using electrochemical impedance spectroscopy. The proposed method was also applied to determine the zeta-potential of charged nanoparticles with an average diameter of 110 nm. This simple method for determining liquid conductivity could be widely employed in various electrochemical applications.

Multi-channel microfluidic chip coupling with mass spectrometry for simultaneous electro-sprays and extraction

Considering the advantages and research status of microfluidic chip coupling with mass spectrometry (MS), a microfluidic chip-based multi-channel ionization (MCMCI) for the extraction of untreated compounds in complex matrices without sample pretreatments was developed. Quantitative analysis of human urine spiked with various rhodamine B concentrations was also performed, and good linearity was obtained. Comparing to the macro ionization device, MCMCI significantly improved the integration of ionization source, simplified the operation of such a device, and greatly increased the signal intensity with much lower gas pressure. Comparison of our MCMCI with two and three gas channels indicated that the liquid–liquid extraction process before spraying and after spraying produced similar MS results. Moreover, this MCMCI with three gas channels also implemented simultaneous dual sprays with high DC voltages, the interference of two samples was minor and ion suppression effect was drastically alleviated. Such advantages may easily enable internal calibration for accurate mass measurement. Furthermore, dual extraction can be implemented by integrating such multi-spray configuration, which can improve the extracted signal intensity and sensitivity. These technologies open up new avenues for the application of microfluidic chip coupling with MS.

The Development of Fibers That Mimic the Core–Sheath and Spindle‐Knot Morphology of Artificial Silk Using Microfluidic Devices

Spider and silkworm produce diverse silk fibers from spinning dopes through smart spinnerets. Spider's capture silk is composed of core thread and periodic spindle‐knots, while silkworm silk consists of fibroin core and sericin outer layer. To mimic the morphologies of natural heterostructured silks, artificial fibers are dry‐spun using a multichannel microfluidic chip, served with a highly viscous core solution of regenerated silk fibroin and low viscosity sheath solution of sericin. Silk fibers with core–sheath, groove, and spindle‐knot structures are obtained by controlling the flow rates and viscosities of the two microfluids depending on the laminar flow, Kelvin–Helmholtz instability, or Plateau–Rayleigh instability.

High-Throughput Contact Flow Lithography.

High-throughput fabrication of graphically encoded hydrogel microparticles is achieved by combining flow contact lithography in a multichannel microfluidic device and a high capacity 25 mm LED UV source. Production rates of chemically homogeneous particles are improved by two orders of magnitude. Additionally, the custom-built contact lithography instrument provides an affordable solution for patterning complex microstructures on surfaces.

Application of a multi-channel microfluidic chip on the simultaneous detection of DNAs by using microbead-quantum dots.

Several researches have shown that cancer is caused by genetic mutations especially in genes involved in cell growth and regulation. Ras family members are frequently found in their mutated, oncogenic forms in human tumors. Mutant RAS proteins are constitutively active, owing to reduce intrinsic GTPase activity and insensitivity to GTPase-activating protein (GAPs). In total, activating mutations in the RAS genes occur in approximately 20% of all human cancers, mainly in codon 12, 13 or 61. Activating mutations in the NRAS gene not only result in the reduction of intrinsic GTPase activity but also in the induction of resistance against molecules inducing such activity. In this paper, we reported a rapid, simple and portable method for detecting the mutant types of NRAS genes codon 12 and 61 simultaneously by using bead-quantum dots (QDs) based multi-channel microfluidic chip. Probe DNAs are conjugated to bead-QDs and packed in the pillars of channels in the microfluidic chip. After injection of target DNAs and intercalating dyes, the fluorescence quenching of QDs by intercalating dye was observed due to FRET phenomena. The platform can be effortlessly applied in other biological and clinical areas.

Immuno-capture and in situ detection of Salmonella typhimurium on a novel microfluidic chip

The new method presented in this article achieved the goal of capturing Salmonella typhimurium via immunoreaction and rapid in situ detection of the CdSe/ZnS quantum dots (QDs) labeled S. typhimurium by self-assembly light-emitting diode-induced fluorescence detection (LIF) microsystem on a specially designed multichannel microfluidic chip. CdSe/ZnS QDs were used as fluorescent markers improving detection sensitivity. The microfluidic chip developed in this study was composed of 12 sample channels, 3 mixing zones, and 6 immune reaction zones, which also acted as fluorescence detection zones. QDs–IgG–primary antibody complexes were generated by mixing CdSe/ZnS QDs conjugated secondary antibody (QDs–IgG) and S. typhimurium antibody (primary antibody) in mixing zones. Then, the complexes went into immune reaction zones to label previously captured S. typhimurium in the sandwich mode. The capture rate of S. typhimurium in each detection zone was up to 70%. The enriched QDs-labeled S. typhimurium was detected using a self-assembly LIF microsystem. A good linear relationship was obtained in the range from 3.7×10 to 3.7×105cfumL−1 using the equation I=0.1739 log (C)−0.1889 with R2=0.9907, and the detection limit was down to 37cfumL−1. The proposed method of online immunolabeling with QDs for in situ fluorescence detection on the designed multichannel microfluidic chip had been successfully used to detect S. typhimurium in pork sample, and it has shown potential advantages in practice.

Multi-channel PMMA microfluidic biosensor with integrated IDUAs for electrochemical detection.

A novel multi-channel poly(methyl methacrylate) (PMMA) microfluidic biosensor with interdigitated ultramicroelectrode arrays (IDUAs) for electrochemical detection was developed. The focus of the development was a simple fabrication procedure and the realization of a reliable large IDUA that can provide detection simultaneously to several microchannels. As proof of concept, five microchannels are positioned over a large single IDUA where the channels are parallel with the length of the electrode finger. The IDUAs were fabricated on the PMMA cover piece and bonded to a PMMA substrate containing the microfluidic channels using UV/ozone-assisted thermal bonding. Conditions of device fabrication were optimized realizing a rugged large IDUA within a bonded PMMA device. Gold adhesion to the PMMA, protective coatings, and pressure during bonding were optimized. Its electrochemical performance was studied using amperometric detection of potassium ferri and ferro hexacyanide. Cumulative signals within the same chip showed very good linearity over a range of 0-38 μM (R(2) = 0.98) and a limit of detection of 3.48 μM. The bonding of the device was optimized so that no cross talk between the channels was observed which otherwise would have resulted in unreliable electrochemical responses. The highly reproducible signals achieved were comparable to those obtained with separate single-channel devices. Subsequently, the multi-channel microfluidic chip was applied to a model bioanalytical detection strategy, i.e., the quantification of specific nucleic acid sequences using a sandwich approach. Here, probe-coated paramagnetic beads and probe-tagged liposomes entrapping ferri/ferro hexacyanide as the redox marker were used to bind to a single-stranded DNA sequence. Flow rates of the non-ionic detergent n-octyl-β-D-glucopyranoside for liposome lysis were optimized, and the detection of the target sequences was carried out coulometrically within 250 s and with a limit of detection of 12.5 μM. The robustness of the design and the reliability of the results obtained in comparison to previously published single-channel designs suggest that the multi-channel device offers an excellent opportunity for bioanalytical applications that require multianalyte detection and high-throughput assays.

Direct and sensitive detection of foodborne pathogens within fresh produce samples using a field-deployable handheld device

Direct and sensitive detection of foodborne pathogens from fresh produce samples was accomplished using a handheld lab-on-a-chip device, requiring little to no sample processing and enrichment steps for a near-real-time detection and truly field-deployable device. The detection of Escherichia coli K12 and O157:H7 in iceberg lettuce was achieved utilizing optimized Mie light scatter parameters with a latex particle immunoagglutination assay. The system exhibited good sensitivity, with a limit of detection of 10CFUmL−1 and an assay time of <6min. Minimal pretreatment with no detrimental effects on assay sensitivity and reproducibility was accomplished with a simple and cost-effective KimWipes filter and disposable syringe. Mie simulations were used to determine the optimal parameters (particle size d, wavelength λ, and scatter angle θ) for the assay that maximize light scatter intensity of agglutinated latex microparticles and minimize light scatter intensity of the tissue fragments of iceberg lettuce, which were experimentally validated. This introduces a powerful method for detecting foodborne pathogens in fresh produce and other potential sample matrices. The integration of a multi-channel microfluidic chip allowed for differential detection of the agglutinated particles in the presence of the antigen, revealing a true field-deployable detection system with decreased assay time and improved robustness over comparable benchtop systems. Additionally, two sample preparation methods were evaluated through simulated field studies based on overall sensitivity, protocol complexity, and assay time. Preparation of the plant tissue sample by grinding resulted in a two-fold improvement in scatter intensity over washing, accompanied with a significant increase in assay time: ∼5min (grinding) versus ∼1min (washing). Specificity studies demonstrated binding of E. coli O157:H7 EDL933 to only O157:H7 antibody conjugated particles, with no cross-reactivity to K12. This suggests the adaptability of the system for use with a wide variety of pathogens, and the potential to detect in a variety of biological matrices with little to no sample pretreatment.