Toward the Ultimate Limit of Analyte Detection, in Graphene-Based Field-Effect Transistors.

The ultimate sensitivity of field-effect-transistor (FET)-based devices for ionic species detection is of great interest, given that such devices are capable of monitoring single-electron-level modulations. It is shown here, from both theoretical and experimental perspectives, that for such ultimate limits to be approached the thermodynamic as well as kinetic characteristics of the (FET surface)-(linker)-(ion-receptor) ensemble must be considered. The sensitivity was probed in terms of optimal packing of the ensemble, through a minimal charge state/capacitance point of view and atomic force microscopy. Through the fine-tuning of the linker and receptor interaction with the sensing surface, a record limit of detection as well as specificity in the femtomolar range, orders of magnitude better than previously obtained and in excellent accord with prediction, was observed.

Imputation of missing values in lipidomic datasets.

Lipidomic data often exhibit missing data points, which can be categorized as missing completely at random (MCAR), missing at random, or missing not at random (MNAR). In order to utilize statistical methods that require complete datasets or to improve the identification of potential effects in statistical comparisons, imputation techniques can be employed. In this study, we investigate commonly used methods such as zero, half-minimum, mean, and median imputation, as well as more advanced techniques such as k-nearest neighbor and random forest imputation. We employ a combination of simulation-based approaches and application to real datasets to assess the performance and effectiveness of these methods. Shotgun lipidomics datasets exhibit high correlations and missing values, often due to low analyte abundance, characterized as MNAR. In this context, k-nearest neighbor approaches based on correlation and truncated normal distributions demonstrate best performance. Importantly, both methods can effectively impute missing values independent of the type of missingness, the determination of which is nearly impossible in practice. The imputation methods still control the type I error rate.

Rapid detection of Mucorales in human blood and urine samples by functionalized Heusler magnetic nanoparticle assisted customized loop-mediated isothermal amplification.

Mucormycosis is a rare disease with scarce diagnostic methods for early intervention. Available strategies employing direct microscopy using calcofluor white-KOH, culture, radiologic, and histopathologic testing often are time-intensive and demand intricate protocols. Nucleic Acid Amplification Test holds promise due to its high sensitivity combined with rapid detection. Loop-mediated isothermal amplification (LAMP) based detection offers an ultrasensitive technique that does not require complicated thermocyclers like in polymerase chain reaction, offering a straightforward means for improving diagnoses as a near-point-of-care test. The study introduces a novel magnetic nanoparticle-based LAMP assay for carryover contaminant capture to reduce false positives. Solving the main drawback of LAMP-based diagnosis techniques. The assay targets the cotH gene, which is invariably specific to Mucorales. The assay was tested with various species of Mucorales, and the limit of detections for Rhizopus microsporus, Lichtheimia corymbifera, Rhizopus arrhizus, Rhizopus homothallicus, and Cunninghamella bertholletiae were 1 fg, 1 fg, 0.1 pg, 0.1 pg, and 0.01 ng, respectively. This was followed by a clinical blindfolded study using whole blood and urine samples from 30 patients diagnosed with Mucormycosis. The assay has a high degree of repeatability and had an overall sensitivity of > 83%. Early Mucormycosis detection is crucial, as current lab tests from blood and urine lack sensitivity and take days for confirmation despite rapid progression and severe complications. Our developed technique enables the confirmation of Mucormycosis infection in < 45 min, focusing specifically on the RT-LAMP process. Consequently, this research offers a viable technique for quickly identifying Mucormycosis from isolated DNA of blood and urine samples instead of invasive tissue samples.

Mucormycosis is a challenging disease to diagnose early. This study introduces a sensitive and rapid diagnostic approach using Loop-mediated isothermal amplification technology. Testing blood and urine samples from 30 patients revealed promising sensitivity and repeatability, indicating its potential for non-invasive diagnosis.

A Highly Selective Schiff Base Based Chemodosimeter for the Detection of Perfluorooctanoic Acid by Optical Biosensor.

A simple imine derivative based sensor (IDP) has been synthesized and characterized by 1 H NMR, 13 C NMR and mass spectral techniques. IDP is more capable of detecting perfluorooctanoic acid (PFOA) in a selective and sensitive manner. The PFOA as a biomarker interacts with IDP and shows "TURN-ON" response by colorimetric and fluorimetric method. Under optimized experimental observations, the selective determination of PFOA using IDP among other competitors as biomolecules has been noticed. The detection limit is 0.31 × 10- 8 mol/L. The practical applications of the IDP is effectively evaluated in human biofluids and water samples.

Spectroscopic Investigation of Coumarin Based Novel Fluorescent TURN OFF Sensor for the Selective Detection of Fe3+: In-vitro Live Cell Imaging Application.

The novel TURN-OFF fluorescent sensors 4-(Benzo[1,3]dioxol-5-yloxymethyl)-7-hydroxy-chromen-2-one (4BHC) and 4-(6-Bromo-benzo[1,3]dioxol-5-yloxymethyl)-7-hydroxy-chromen-2-one (4BBHC) are designed and synthesized for the spectrofluorometric detection of the biologically important Fe3+ ions, which has sensitive and selective fluorescence quenching over other competitive metal ions. The effectiveness of the sensors and rapid response are validated through UV-Visible, and fluorescence spectral changes. These spectral changes could be due to the formation of coordination bond between ligand and metal ion. The binding stoichiometry of both sensors with Fe3+ ions is studied with the help of Job's plot, which gives a 1:2 coordination ratio; this is further confirmed through DFT, IR and NMR studies. The association constants of 4BHC and 4BBHC are calculated through Benesie-Hildebrand plots, and they are found to be 6 × 104 M-1 and 11.2 × 104 M-1 respectively. Following, LOD is calculated to define the range of sensitivity of the proposed sensors and is found to be 3.43 µM and 2.14 µM respectively. The chemical hardness parameter suggested that both sensors are soft molecules. In addition, low cytotoxicity levels of 4BHC and 4BBHC led to the demonstration of their efficacy in In-Vitro imaging of Fe3+ ions inside living cells, which ensures that these sensors are promising candidates for bioimaging.

Immunoassays: Analytical and Clinical Performance, Challenges, and Perspectives of SERS Detection in Comparison with Fluorescent Spectroscopic Detection.

Immunoassays (IAs) with fluorescence-based detection are already well-established commercialized biosensing methods, such as enzyme-linked immunosorbent assay (ELISA) and lateral flow immunoassay (LFIA). Immunoassays with surface-enhanced Raman spectroscopy (SERS) detection have received significant attention from the research community for at least two decades, but so far they still lack a wide clinical commercial application. This review, unlike any other review that we have seen, performs a three-dimensional performance comparison of SERS IAs vs. fluorescence IAs. First, we compared the limit of detection (LOD) as a key performance parameter for 30 fluorescence and 30 SERS-based immunoassays reported in the literature. We also compared the clinical performances of a smaller number of available reports for SERS vs. fluorescence immunoassays (FIAs). We found that the median and geometric average LODs are about 1.5-2 orders of magnitude lower for SERS-based immunoassays in comparison to fluorescence-based immunoassays. For instance, the median LOD for SERS IA is 4.3 × 10-13 M, whereas for FIA, it is 1.5 × 10-11 M. However, there is no significant difference in average relative standard deviation (RSD)-both are about 5-6%. The analysis of sensitivity, selectivity, and accuracy reported for a limited number of the published clinical studies with SERS IA and FIA demonstrates an advantage of SERS IA over FIA, at least in terms of the median value for all three of those parameters. We discussed common and specific challenges to the performances of both SERS IA and FIA, while proposing some solutions to mitigate those challenges for both techniques. These challenges include non-specific protein binding, non-specific interactions in the immunoassays, sometimes insufficient reproducibility, relatively long assay times, photobleaching, etc. Overall, this review may be useful for a large number of researchers who would like to use immunoassays, but particularly for those who would like to make improvements and move forward in both SERS-based IAs and fluorescence-based IAs.

[Verification Study of the Detection Method for Unauthorized Genetically Modified Papaya by Combining DNA Polymerases and Real-time PCR Instruments].

In the Japanese official detection method for unauthorized genetically modified (GM) papayas, one of two types of real-time PCR reagents with DNA polymerase (TaqMan Gene Master Mix [TaqMan Gene] or FastGene QPCR Probe Mastermix w/ROX [FastGene]) is primarily used for measurement. In 2022, we conducted a laboratory performance study on the unauthorized GM papaya line PRSV-YK, and the results revealed that high threshold cycle (Cq) values for the PRSV-YK detection test were obtained using TaqMan Gene with the 7500 Fast & 7500 Real-Time PCR System (ABI7500) and QuantStudio 12K Flex (QS12K), indicating the possibility of false negatives. The possibility of similar problems with all unauthorized GM papaya lines detection tests needs to be evaluated. In this study, we performed detection tests on unauthorized GM papaya lines (PRSV-YK, PRSV-SC, and PRSV-HN), the cauliflower mosaic virus 35S promotor (CaM), and a papaya positive control (Chy), and examined how the limits of detection (LOD) for each test are affected by two types of DNA polymerases (TaqMan Gene and FastGene) and three types of real-time PCR instruments (ABI7500, QS12K, and LightCycler 480 Instrument II [LC480]). In the PRSV-YK and PRSV-SC detection tests using ABI7500 and QS12K, measurement with TaqMan Gene showed a higher LOD than FastGene. In this case, an exponential amplification curve was confirmed on the amplification plot; however, the amplification curve did not cross the ΔRn threshold line and the correct Cq value was not obtained with a threshold line=0.2. The other tests (PRSV-HN, CaM, and Chy with ABI7500 and QS12K, and all detection tests with LC480) showed no important differences in the LOD for each test using either DNA polymerase. Therefore, when performing PRSV-YK and PRSV-SC detection tests with the ABI7500 or QS12K, FastGene should be used to avoid false negatives for foods containing GM papaya lines PRSV-YK and PRSV-SC at low mixing levels.

PATHPOD - A loop-mediated isothermal amplification (LAMP)-based point-of-care system for rapid clinical detection of SARS-CoV-2 in hospitals in Denmark.

Sensitive and rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a vital goal in the ongoing COVID-19 pandemic. We present in this comprehensive work, for the first time, detailed fabrication and clinical validation of a point of care (PoC) device for rapid, onsite detection of SARS-CoV-2 using a real-time reverse-transcription loop-mediated isothermal amplification (RT-LAMP) reaction on a polymer cartridge. The PoC system, namely PATHPOD, consisting of a standalone device (weight less than 1.2 kg) and a cartridge, can perform the detection of 10 different samples and two controls in less than 50 min, which is much more rapid than the golden standard real-time reverse-transcription Polymerase Chain Reaction (RT-PCR), typically taking 16-48 h. The novel total internal reflection (TIR) scheme and the reactions inside the cartridge in the PoC device allow monitoring of the diagnostic results in real-time and onsite. The analytical sensitivity and specificity of the PoC test are comparable with the current RT-PCR, with a limit of detection (LOD) down to 30-50 viral genome copies. The robustness of the PATHPOD PoC system has been confirmed by analyzing 398 clinical samples initially examined in two hospitals in Denmark. The clinical sensitivity and specificity of these tests are discussed.

Fluorophore-encapsulated nanobeads for on-site, rapid, and sensitive lateral flow assay.

Since December 2019, the rapid and sensitive detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a priority for public health. Although the lateral flow assay (LFA) sensor has emerged as a rapid and on-site SARS-CoV-2 detection technique, the conventional approach of using gold nanoparticles for the signaling probe had limitations in increasing the sensitivity of the sensor. Herein, our newly suggested methodology to improve the performance of the LFA system could amplify the sensor signal with a facile fabrication method by concentrating fluorescent organic molecules. A large Stokes shift fluorophore (single benzene) was encapsulated into polystyrene nanobeads to enhance the fluorescence intensity of the probe for LFA sensor, which was detected on the test line with a longpass filter under ultraviolet light irradiation. This approach provides comparatively high sensitivity with the limit of detection of 1 ng mL-1 for the SARS-CoV-2 spike protein and a fast detection process, which takes less than 20 min. Furthermore, our sensor showed higher performance than gold nanoparticle-based commercial rapid diagnostics test kits in clinical tests, proving that this approach is more suitable and reliable for the sensitive and rapid detection of viruses, bacteria, and other hazardous materials.

Green synthesis of naphthyl derivative as an optical sensor for the detection of l-carnitine in food samples.

An economical and green approach to the synthesis of naphthyl derivative for detection of l-carnitine (3-hydroxy-4-N-trimethyl-aminobutyrate) is practically important. We developed a naphthyl derivative as a probe showing 'turn-on' response towards l-carnitine selectively at pH 7.2 through ICT mechanism with a good limit of detection (LOD) of 0.126 µM. Using Job's plot for determining the binding stoichiometry, it was found that probe could form a more stable complex (1:1) with carnitine. The binding constant (K) between probe and carnitine was calculated as 8 × 107  M-1 using the Benesi-Hildebrand plot. The binding interaction of the probe with l-carnitine was confirmed by nuclear magnetic resonance titrations, Fourier-transform infrared spectroscopy, photo physical studies and density functional theory calculations. Meanwhile, the probe can be used to quantitatively detect carnitine in food samples.

Optimizing an Optical Cavity-Based Biosensor for Enhanced Sensitivity.

The rapid advancement of biosensor technology has revolutionized healthcare, offering improved sensitivity, specificity, and portability. We have developed an optical cavity-based biosensor (OCB) as a promising solution due to its label-free detection, high sensitivity, real-time monitoring, multiplexing capability, and versatility. The OCB consists of an optical cavity structure (OCS), optical components, and a low-cost camera. The OCS is created by two partially reflective surfaces separated by a small gap, where the interaction between target analytes and immobilized receptors leads to a shift in the resonance transmission spectrum, caused by minute changes in the local refractive index (RI). In our previous work, we successfully detected these small changes with a simple OCS and cost-effective components using a differential detection method. Building upon these achievements, this study focuses on optimizing the OCS, improving the camera settings, and enhancing the differential detection approach. By increasing the reflectance of the surfaces and optimizing the optical cavity widths correspondingly, we achieved an improved limit of detection (LOD). We also investigated how the charge-coupled device (CCD) camera shutter time affects the LOD. Additionally, we introduced a new differential equation to further enhance the sensitivity of our system. Through these advancements, we could improve the LOD of the OCB by 7.2 times, specifically for an OCS with a cavity thickness of 9.881 µm and a silver thickness of 46.87 nm. These findings not only contribute to the ongoing effort of optimizing the OCB, but also pave the way for the development of advanced point-of-care biosensors with enhanced detection capabilities.

Emerging Methods in Biosensing of Immunoglobin G-A Review.

Human antibodies are produced due to the activation of immune system components upon exposure to an external agent or antigen. Human antibody G, or immunoglobin G (IgG), accounts for 75% of total serum antibody content. IgG controls several infections by eradicating disease-causing pathogens from the body through complementary interactions with toxins. Additionally, IgG is an important diagnostic tool for certain pathological conditions, such as autoimmune hepatitis, hepatitis B virus (HBV), chickenpox and MMR (measles, mumps, and rubella), and coronavirus-induced disease 19 (COVID-19). As an important biomarker, IgG has sparked interest in conducting research to produce robust, sensitive, selective, and economical biosensors for its detection. To date, researchers have used different strategies and explored various materials from macro- to nanoscale to be used in IgG biosensing. In this review, emerging biosensors for IgG detection have been reviewed along with their detection limits, especially electrochemical biosensors that, when coupled with nanomaterials, can help to achieve the characteristics of a reliable IgG biosensor. Furthermore, this review can assist scientists in developing strategies for future research not only for IgG biosensors but also for the development of other biosensing systems for diverse targets.

The HBIM-GIS Main10ance Platform to Enhance the Maintenance and Conservation of Historical Built Heritage.

This paper aims to describe the outcomes of the Main10ance project, which focused on developing an integrated HBIM-GIS platform to support the maintenance and conservation plans for the historic built heritage. The pilot case is the UNESCO complex of the Sacri Monti, located in northern Italy and Switzerland, which consists of groups of chapels and architectural artifacts holding significant historical and cultural value. Given their importance, specific maintenance plans involving multiple stakeholders and specialists are required. This study focuses on creating a unified system that semantically and spatially describes the architectural elements of the case study and the surrounding context and indoor assets. After a 3D integrated metric survey and the related data processing, parametric 3D models were created in a BIM environment, and a spatial database was developed to incorporate both geometric and alphanumeric entities. The database enables interoperability among different actors and domains, gathering heritage-related information crucial for restoration and conservation purposes. Additionally, the custom 4MAIN10ANCE web platform was developed with different levels of details (LODs), enabling the retrieval of both 2D and 3D data and establishing connections between the BIM models of the chapels and associated information.

Aluminum Foil vs. Gold Film: Cost-Effective Substrate in Sandwich SERS Immunoassays of Biomarkers Reveals Potential for Selectivity Improvement.

The first application of aluminum foil (Al F) as a low-cost/high-availability substrate for sandwich immunoassay using surface-enhanced Raman spectroscopy (SERS) is reported. Untreated and unmodified Al F and gold film are used as substrates for sandwich SERS immunoassay to detect tuberculosis biomarker MPT64 and human immunoglobulin (hIgG) in less than 24 h. The limits of detection (LODs) for tuberculosis (TB) biomarker MPT64 on Al foil, obtained with commercial antibodies, are about 1.8-1.9 ng/mL, which is comparable to the best LOD (2.1 ng/mL) reported in the literature for sandwich ELISA, made with fresh in-house antibodies. Not only is Al foil competitive with traditional SERS substrate gold for the sandwich SERS immunoassay in terms of LOD, which is in the range 18-30 pM or less than 1 pmol of human IgG, but it also has a large cost/availability advantage over gold film. Moreover, human IgG assays on Al foil and Si showed better selectivity (by about 30-70% on Al foil and at least eightfold on Si) and a nonspecific response to rat or rabbit IgG, in comparison to the selectivity in assays using gold film.

Machine Learning-Based Fragment Selection Improves the Performance of Qualitative PRM Assays.

Targeted mass spectrometry-based platforms have become a valuable tool for the sensitive and specific detection of protein biomarkers in clinical and research settings. Traditionally, developing a targeted assay for peptide quantification has involved manually preselecting several fragment ions and establishing a limit of detection (LOD) and a lower limit of quantitation (LLOQ) for confident detection of the target. Established thresholds such as LOD and LLOQ, however, inherently sacrifice sensitivity to afford specificity. Here, we demonstrate that machine learning can be applied to qualitative PRM assays to discriminate positive from negative samples more effectively than a traditional approach utilizing conventional methods. To demonstrate the utility of this method, we trained an ensemble machine learning model using 282 SARS-CoV-2 positive and 994 SARS-CoV-2 negative nasopharyngeal swabs (NP swab) analyzed using a targeted PRM method. This model was then validated using an independent set of 200 positive and 150 negative samples and achieved a sensitivity of 92% relative to results obtained by RT-PCR, which was superior to a traditional approach that resulted in 86.5% sensitivity when analyzing the same data. These results demonstrate that machine learning can be applied to qualitative PRM assays and results in superior performance relative to traditional methods.

Development of Optical Biosensor for the Detection of Glutamine in Human Biofluids Using Merocyanine Dye.

Merocyanine dye based fluorescent organic compound has been synthesized for the detection of glutamine. The probe showed remarkable fluorescent intensity with glutamine through ICT (Intermolecular Charge Transfer Mechanism). Hence, it is tested for the detection of glutamine using colorimetric and fluorimetric techniques in physiological and neutral pH (7.2). Under optimized experimental conditions, the probe detects glutamine selectively among other interfering biomolecules. The probe has showed a LOD (lower limit of detection) of 9.6 × 10-8 mol/L at the linear range 0-180 µM towards glutamine. The practical application of the probe is successfully tested in human biofluids.

Development and evaluation of real-time recombinase polymerase amplification assay for rapid and sensitive detection of Vibro mimicus in human plasma samples.

AIM: We aimed at developing a fast and accurate method to detect Vibrio mimicus using real-time recombinase polymerase amplification assay. METHODS AND RESULTS: Specific primers and probe were designed to target V. mimicus haemolysin (vmh) gene. Target DNA was successfully amplified at 41°C within 20 min. The method exhibited a high level of specificity and the sensitivity was 2.1 × 102 copies/25 µl or 8.4 copies/µl, which is in line with real-time polymerase chain reaction (PCR). The calibration curve plotted by the second-order polynomial regression showed better than the linear curve, as the correlation coefficient was raised to 0.9907, which suggested that the second-order polynomial regressions might be considered to apply to the quantification of real-time recombinase polymerase amplification (RPA). The limit of detection (LOD) was predicted to be 77 copies/25 µl or 3 copies/µl by a probit model. The limit of quantification (LOQ) was calculated to be 28 copies /25 µl or 1 copies/µl by a receiver operating characteristic (ROC) curve, which firstly make LOQ could be available to real-time RPA. For the performance of the real-time RPA in plasma samples, the detection sensitivity of real-time RPA was as good as the real-time PCR. For pretreatment of plasma samples, the boiling method was better than using kits, as it further shortened the time of the real-time RPA in detecting V. mimicus. CONCLUSIONS: The real-time RPA assay developed in our study shows multiple advantages over currently available DNA diagnostic method, including a quicker time-to-result for a single sample, requiring minimal infrastructure and technical support and being tolerant to inhibitors in plasma samples. SIGNIFICANCE AND IMPACT OF THE STUDY: The real-time RPA assay developed here is a potentially valuable tool for point-of-care (POC) diagnosis of V. mimicus infection in endemic field, especially in the resources-limited settings, as combined with portable devices.

CRISPR-Cas13a cascade-based viral RNA assay for detecting SARS-CoV-2 and its mutations in clinical samples.

SARS-CoV-2 is one of the greatest threats to global human health. Point-of-care diagnostic tools for SARS-CoV-2 could facilitate rapid therapeutic intervention and mitigate transmission. In this work, we report CRISPR-Cas13a cascade-based viral RNA (Cas13C) assay for label-free and isothermal determination of SARS-CoV-2 and its mutations in clinical samples. Cas13a/crRNA was utilized to directly recognize the target of SARS-CoV-2 RNA, and the recognition events sequentially initiate the transcription amplification to produce light-up RNA aptamers for output fluorescence signal. The recognition of viral RNA via Cas13a-guide RNA ensures a high specificity to distinguish SARS-CoV-2 from MERS-CoV and SARS-CoV, as well as viral mutations. A post transcription amplification strategy was triggered after CRISPR-Cas13a recognition contributes to an amplification cascade that achieves high sensitivity for detecting SARS-CoV-2 RNA, with a limit of detection of 0.216 fM. In addition, the Cas13C assay could be able to discriminate single-nucleotide mutation, which was proven with N501Y in SARS-Cov-2 variant. This method was validated by a 100% agreement with RT-qPCR results from 12 clinical throat swab specimens. The Cas13C assay has the potential to be used as a routine nucleic acid test of SARS-CoV-2 virus in resource-limited regions.

Equipment-free, salt-mediated immobilization of nucleic acids for nucleic acid lateral flow assays.

As the world has been facing several deadly virus crises, including Zika virus disease, Ebola virus disease, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and Coronavirus disease 2019 (COVID-19), lateral flow assays (LFAs), which require minimal equipment for point-of-care of viral infectious diseases, are garnering much attention. Accordingly, there is an increasing demand to reduce the time and cost required for manufacturing LFAs. The current study introduces an equipment-free method of salt-mediated immobilization of nucleic acids (SAIoNs) for LFAs. Compared to general DNA immobilization methods such as streptavidin-biotin, UV-irradiation, and heat treatment, our method does not require special equipment (e.g., centrifuge, UV-crosslinker, heating device); therefore, it can be applied in a resource-limited environment with reduced production costs. The immobilization process was streamlined and completed within 30 min. Our method improved the color intensity signal approximately 14 times compared to the method without using SAIoNs and exhibited reproducibility with the long-term storage stability. The proposed method can be used to detect practical targets (e.g., SARS-CoV-2) and facilitates highly sensitive and selective detection of target nucleic acids with multiplexing capability and without any cross-reactivity. This novel immobilization strategy provides a basis for easily and inexpensively developing nucleic acid LFAs combined with various types of nucleic acid amplification.

Ultrasensitive dopamine detection with graphene aptasensor multitransistor arrays.

Detecting physiological levels of neurotransmitters in biological samples can advance our understanding of brain disorders and lead to improved diagnostics and therapeutics. However, neurotransmitter sensors for real-world applications must reliably detect low concentrations of target analytes from small volume working samples. Herein, a platform for robust and ultrasensitive detection of dopamine, an essential neurotransmitter that underlies several brain disorders, based on graphene multitransistor arrays (gMTAs) functionalized with a selective DNA aptamer is presented. High-yield scalable methodologies optimized at the wafer level were employed to integrate multiple graphene transistors on small-size chips (4.5 × 4.5 mm). The multiple sensor array configuration permits independent and simultaneous replicate measurements of the same sample that produce robust average data, reducing sources of measurement variability. This procedure allowed sensitive and reproducible dopamine detection in ultra-low concentrations from small volume samples across physiological buffers and high ionic strength complex biological samples. The obtained limit-of-detection was 1 aM (10-18) with dynamic detection ranges spanning 10 orders of magnitude up to 100 µM (10-8), and a 22 mV/decade peak sensitivity in artificial cerebral spinal fluid. Dopamine detection in dopamine-depleted brain homogenates spiked with dopamine was also possible with a LOD of 1 aM, overcoming sensitivity losses typically observed in ion-sensitive sensors in complex biological samples. Furthermore, we show that our gMTAs platform can detect minimal changes in dopamine concentrations in small working volume samples (2 µL) of cerebral spinal fluid samples obtained from a mouse model of Parkinson's Disease. The platform presented in this work can lead the way to graphene-based neurotransmitter sensors suitable for real-world academic and pre-clinical pharmaceutical research as well as clinical diagnosis.