A Multidisciplinary Approach toward CMOS Capacitive Sensor Array for Droplet Analysis.

This paper introduces an innovative method for the analysis of alcohol-water droplets on a CMOS capacitive sensor, leveraging the controlled thermal behavior of the droplets. Using this sensing method, the capacitive sensor measures the total time of evaporation (ToE), which can be influenced by the droplet volume, temperature, and chemical composition. We explored this sensing method by introducing binary mixtures of water and ethanol or methanol across a range of concentrations (0-100%, with 10% increments). The experimental results indicate that while the capacitive sensor is effective in measuring both the total ToE and dielectric properties, a higher dynamic range and resolution are observed in the former. Additionally, an array of sensing electrodes successfully monitors the droplet-sensor surface interaction. However practical considerations such as the creation of parasitic capacitance due to mismatch, arise from the large sensing area in the proposed capacitive sensors and other similar devices. In this paper, we discuss this non-ideality and propose a solution. Also, this paper showcases the benefits of utilizing a CMOS capacitive sensing method for accurately measuring ToE.

Design and Analysis of a Low-Voltage VCO: Reliability and Variability Performance.

This paper investigates an adaptive body biasing (ABB) circuit to improve the reliability and variability of a low-voltage inductor-capacitor (LC) voltage-controlled oscillator (VCO). The ABB circuit provides VCO resilience to process variability and reliability variation through the threshold voltage adjustment of VCO's transistors. Analytical equations considering the body bias effect are derived for the most important relations of the VCO and then the performance is verified using the post-layout simulation results. Under a 0.16% threshold voltage shift, the sensitivity of the normalized phase noise and transconductance of the VCO with the ABB circuit compared to the constant body bias (CBB) decreases by around 8.4 times and 3.1 times, respectively. Also, the sensitivity of the normalized phase noise and transconductance of the proposed VCO under 0.16% mobility variations decreases by around 1.5 times and 1.7 times compared to the CBB, respectively. The robustness of the VCO is also examined using process variation analysis through Monte Carlo and corner case simulations. The post-layout results in the 180 nm CMOS process indicate that the proposed VCO draws a power consumption of only 398 µW from a 0.6 V supply when the VCO frequency is 2.4 GHz. It achieves a phase noise of -123.19 dBc/Hz at a 1 MHz offset and provides a figure of merit (FoM) of -194.82 dBc/Hz.

Emerging Field-Effect Transistor Biosensors for Life Science Applications.

Field-effect transistors (FETs) have gained significant interest and hold great potential as groundbreaking sensing technology in the fields of biosensing and life science research [...].

CoVSense: Ultrasensitive Nucleocapsid Antigen Immunosensor for Rapid Clinical Detection of Wildtype and Variant SARS-CoV-2.

The widespread accessibility of commercial/clinically-viable electrochemical diagnostic systems for rapid quantification of viral proteins demands translational/preclinical investigations. Here, Covid-Sense (CoVSense) antigen testing platform; an all-in-one electrochemical nano-immunosensor for sample-to-result, self-validated, and accurate quantification of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N)-proteins in clinical examinations is developed. The platform's sensing strips benefit from a highly-sensitive, nanostructured surface, created through the incorporation of carboxyl-functionalized graphene nanosheets, and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) conductive polymers, enhancing the overall conductivity of the system. The nanoengineered surface chemistry allows for compatible direct assembly of bioreceptor molecules. CoVSense offers an inexpensive (<$2 kit) and fast/digital response (<10 min), measured using a customized hand-held reader (<$25), enabling data-driven outbreak management. The sensor shows 95% clinical sensitivity and 100% specificity (Ct<25), and overall sensitivity of 91% for combined symptomatic/asymptomatic cohort with wildtype SARS-CoV-2 or B.1.1.7 variant (N = 105, nasal/throat samples). The sensor correlates the N-protein levels to viral load, detecting high Ct values of ≈35, with no sample preparation steps, while outperforming the commercial rapid antigen tests. The current translational technology fills the gap in the workflow of rapid, point-of-care, and accurate diagnosis of COVID-19.

A Low-Cost Handheld Impedimetric Biosensing System for Rapid Diagnostics of SARS-CoV-2 Infections.

Current laboratory diagnostic approaches for virus detection give reliable results, but they require a lengthy procedure, trained personnel, and expensive equipment and reagents; hence, they are not a suitable choice for home monitoring purposes. This paper addresses this challenge by developing a portable impedimetric biosensing system for the identification of COVID-19 patients. This sensing system has two main parts: a throwaway two-working electrode (2-WE) strip and a novel read-out circuit, specifically designed for simultaneous signal acquisition from both working electrodes. Highly reliable electrochemical signal tracking from multiplex immunosensors provides a potential for flexible and portable multi-biomarker detection. The electrodes' surfaces were functionalized with SARS-CoV-2 Nucleocapsid Antibody enabling the selective detection of Nucleocapsid protein (N-protein) along with self-validation in the clinical nasopharyngeal swab specimens. The proposed programmable highly sensitive impedance read-out system allows for a wide dynamic detection range, which makes the sensor capable of detecting N-protein concentrations between 0.116 and 10,000 pg/mL. This lightweight and economical read-out arrangement is an ideal prospect for being mass-produced, especially during urgent pandemic situations. Also, such an impedimetric sensing platform has the potential to be redesigned for targeting not only other infectious diseases but also other critical disorders.

A compact, low-cost, and binary sensing (BiSense) platform for noise-free and self-validated impedimetric detection of COVID-19 infected patients.

Electrochemical immuno-biosensors are one of the most promising approaches for accurate, rapid, and quantitative detection of protein biomarkers. The two-working electrode strip is employed for creating a self-supporting system, as a tool for self-validating the acquired results for added reliability. However, the realization of multiplex electrochemical point-of-care testing (ME-POCT) requires advancement in portable, rapid reading, easy-to-use, and low-cost multichannel potentiostat readers. The combined multiplex biosensor strips and multichannel readers allow for suppressing the possible complex matrix effect or ultra-sensitive detection of different protein biomarkers. Herein, a handheld binary-sensing (BiSense) bi-potentiostat was developed to perform electrochemical impedance spectroscopy (EIS)-based signal acquisition from a custom-designed dual-working-electrode immuno-biosensor. BiSense employs a commercially available microcontroller and out-of-shelf components, offering the cheapest yet accurate and reliable time-domain impedance analyzer. A specific electrical board design was developed and customized for impedance signal analysis of SARS-CoV-2 nucleocapsid (N)-protein biosensor in spiked samples and alpha variant clinical nasopharyngeal (NP) swab samples. BiSense showed limit-of-detection (LoD) down to 56 fg/mL for working electrode 1 (WE1) and 68 fg/mL for WE2 and reported with a dynamic detection range of 1 pg/mL to 10 ng/mL for detection of N-protein in spiked samples. The dual biosensing of N-protein in this work was used as a self-validation of the biosensor. The low-cost (∼USD$40) BiSense bi-potentiostat combined with the immuno-biosensors successfully detected COVID-19 infected patients in less than 10 min, with the BiSense reading period shorter than 1.5 min, demonstrating its potential for the realization of ME-POCTs for rapid and hand-held diagnosis of infections.

Oral Cells-On-Chip: Design, Modeling and Experimental Results.

Recent advances in periodontal studies have attracted the attention of researchers to the relation between oral cells and gum diseases, which is a real threat to overall human health. Among various microfabrication technologies, Complementary Metal Oxide Semiconductors (CMOSs) enable the development of low-cost integrated sensors and circuits for rapid and accurate assessment of living cells that can be employed for the early detection and control of periodontal diseases. This paper presents a CMOS capacitive sensing platform that can be considered as an alternative for the analysis of salivatory cells such as oral neutrophils. This platform consists of two sensing electrodes connected to a read-out capacitive circuitry designed and fabricated on the same chip using Austria Mikro Systeme (AMS) 0.35 µm CMOS process. A graphical user interface (GUI) was also developed to interact with the capacitive read-out system and the computer to monitor the capacitance changes due to the presence of saliva cells on top of the chip. Thanks to the wide input dynamic range (IDR) of more than 400 femto farad (fF) and high resolution of 416 atto farad (aF), the experimental and simulation results demonstrate the functionality and applicability of the proposed sensor for monitoring cells in a small volume of 1 µL saliva samples. As per these results, the hydrophilic adhesion of oral cells on the chip varies the capacitance of interdigitated electrodes (IDEs). These capacitance changes then give an assessment of the oral cells existing in the sample. In this paper, the simulation and experimental results set a new stage for emerging sensing platforms for testing oral samples.

A Hybrid Microfluidic Electronic Sensing Platform for Life Science Applications.

This paper presents a novel hybrid microfluidic electronic sensing platform, featuring an electronic sensor incorporated with a microfluidic structure for life science applications. This sensor with a large sensing area of 0.7 mm2 is implemented through a foundry process called Open-Gate Junction FET (OG-JFET). The proposed OG-JFET sensor with a back gate enables the charge by directly introducing the biological and chemical samples on the top of the device. This paper puts forward the design and implementation of a PDMS microfluidic structure integrated with an OG-JFET chip to direct the samples toward the sensing site. At the same time, the sensor's gain is controlled with a back gate electrical voltage. Herein, we demonstrate and discuss the functionality and applicability of the proposed sensing platform using a chemical solution with different pH values. Additionally, we introduce a mathematical model to describe the charge sensitivity of the OG-JFET sensor. Based on the results, the maximum value of transconductance gain of the sensor is ~1 mA/V at Vgs = 0, which is decreased to ~0.42 mA/V at Vgs = 1, all in Vds = 5. Furthermore, the variation of the back-gate voltage from 1.0 V to 0.0 V increases the sensitivity from ~40 mV/pH to ~55 mV/pH. As per the experimental and simulation results and discussions in this paper, the proposed hybrid microfluidic OG-JFET sensor is a reliable and high-precision measurement platform for various life science and industrial applications.

Bi-ECDAQ: An electrochemical dual-immuno-biosensor accompanied by a customized bi-potentiostat for clinical detection of SARS-CoV-2 Nucleocapsid proteins.

Multiplex electrochemical biosensors have been used for eliminating the matrix effect in complex bodily fluids or enabling the detection of two or more bioanalytes, overall resulting in more sensitive assays and accurate diagnostics. Many electrochemical biosensors lack reliable and low-cost multiplexing to meet the requirements of point-of-care detection due to either limited functional biosensors for multi-electrode detection or incompatible readout systems. We developed a new dual electrochemical biosensing unit accompanied by a customized potentiostat to address the unmet need for point-of-care multi-electrode electrochemical biosensing. The two-working electrode system was developed using screen-printing of a carboxyl-rich nanomaterial containing ink, with both working electrodes offering active sites for recognition of bioanalytes. The low-cost bi-potentiostat system (∼$80) was developed and customized specifically to the bi-electrode design and used for rapid, repeatable, and accurate measurement of electrochemical impedance spectroscopy signals from the dual biosensor. This binary electrochemical data acquisition (Bi-ECDAQ) system accurately and selectively detected SARS-CoV-2 Nucleocapsid protein (N-protein) in both spiked samples and clinical nasopharyngeal swab samples of COVID-19 patients within 30 min. The two working electrodes offered the limit of detection of 116 fg/mL and 150 fg/mL, respectively, with the dynamic detection range of 1-10,000 pg/mL and the sensitivity range of 2744-2936 Ω mL/pg.mm2 for the detection of N-protein. The potentiostat performed comparable or better than commercial Autolab potentiostats while it is significantly lower cost. The open-source Bi-ECDAQ presents a customizable and flexible approach towards addressing the need for rapid and accurate point-of-care electrochemical biosensors for the rapid detection of various diseases.

A High Dynamic Range Dual 8×16 Capacitive Sensor Array for Life Science Applications.

This paper presents a fully integrated complementary metal-oxide-semiconductor (CMOS) capacitive sensor array for life science applications. This sensing device consists of an array of 16 × 16 interdigitated electrodes (IDEs) integrated with a charge-based readout and multiplexing circuitries on the same chip. This chip was implemented in 0.35 µm AMS CMOS process. This sensing device has a wide input capacitance range (ICR) of about 100 fF and a resolution of 150 aF, and the capability of temporal, spatial, and dielectric sensing. It makes it possible to develop a low-cost, multimodal, calibration-free sensing platform for life science applications. Here, we demonstrate and discuss the functionality and applicability of the proposed sensing device by introducing various chemical solvents including ethanol, methanol, and pure water. The simulation and experimental results achieved in this work have taken us one step closer to a fully automated calibration-free multimodal capacitive sensing platform for high-throughput drug development and other purposes.

Laser-Induced Graphene-Functionalized Field-Effect Transistor-Based Biosensing: A Potent Candidate for COVID-19 Detection.

Speedy and on-time detection of coronavirus disease 2019 (COVID-19) is of high importance to control the pandemic effectively and stop its disastrous consequences. A widely available, reliable, label-free, and rapid test that can recognize tiny amounts of specific biomarkers might be the solution. Nanobiosensors are one of the most attractive candidates for this purpose. Integration of graphene with biosensing devices shifts the performance of these systems to an incomparable level. Between the various arrangements using this wonder material, field-effect transistors (FETs) display a precise detection even in complex samples. The emergence of pioneering biosensors for detecting a wide range of diseases especially COVID-19 created the incentive to prepare a review of the recent graphene-FET biosensing platforms. However, the graphene fabrication and transfer to the surface of the device is an imperative factor for researchers to take into account. Therefore, we also reviewed the common methods of manufacturing graphene for biosensing applications and discuss their advantages and disadvantages. One of the most recent synthesizing techniques - laser-induced graphene (LIG) - is attracting attention owing to its extraordinary benefits which are thoroughly explained in this article. Finally, a conclusion highlighting the current challenges is presented.

Electronic Sensing Platform (ESP) Based on Open-Gate Junction Field-Effect Transistor (OG-JFET) for Life Science Applications: Design, Modeling and Experimental Results.

This paper presents a new field-effect sensor called open-gate junction gate field-effect transistor (OG-JFET) for biosensing applications. The OG-JFET consists of a p-type channel on top of an n-type layer in which the p-type serves as the sensing conductive layer between two ohmic contacted sources and drain electrodes. The structure is novel as it is based on a junction field-effect transistor with a subtle difference in that the top gate (n-type contact) has been removed to open the space for introducing the biomaterial and solution. The channel can be controlled through a back gate, enabling the sensor's operation without a bulky electrode inside the solution. In this research, in order to demonstrate the sensor's functionality for chemical and biosensing, we tested OG-JFET with varying pH solutions, cell adhesion (human oral neutrophils), human exhalation, and DNA molecules. Moreover, the sensor was simulated with COMSOL Multiphysics to gain insight into the sensor operation and its ion-sensitive capability. The complete simulation procedures and the physics of pH modeling is presented here, being numerically solved in COMSOL Multiphysics software. The outcome of the current study puts forward OG-JFET as a new platform for biosensing applications.

Towards Fully Integrated Portable Sensing Devices for COVID-19 and Future Global Hazards: Recent Advances, Challenges, and Prospects.

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, this fatal disease has been the leading cause of the death of more than 3.9 million people around the world. This tragedy taught us that we should be well-prepared to control the spread of such infectious diseases and prevent future hazards. As a consequence, this pandemic has drawn the attention of many researchers to the development of portable platforms with short hands-on and turnaround time suitable for batch production in urgent pandemic situations such as that of COVID-19. Two main groups of diagnostic assays have been reported for the detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) including nucleic acid-based and protein-based assays. The main focus of this paper is on the latter, which requires a shorter time duration, less skilled technicians, and faces lower contamination. Furthermore, this paper gives an overview of the complementary metal-oxide-semiconductor (CMOS) biosensors, which are potentially useful for implementing point-of-care (PoC) platforms based on such assays. CMOS technology, as a predominant technology for the fabrication of integrated circuits, is a promising candidate for the development of PoC devices by offering the advantages of reliability, accessibility, scalability, low power consumption, and distinct cost.

Recent Advances of Field-Effect Transistor Technology for Infectious Diseases.

Field-effect transistor (FET) biosensors have been intensively researched toward label-free biomolecule sensing for different disease screening applications. High sensitivity, incredible miniaturization capability, promising extremely low minimum limit of detection (LoD) at the molecular level, integration with complementary metal oxide semiconductor (CMOS) technology and last but not least label-free operation were amongst the predominant motives for highlighting these sensors in the biosensor community. Although there are various diseases targeted by FET sensors for detection, infectious diseases are still the most demanding sector that needs higher precision in detection and integration for the realization of the diagnosis at the point of care (PoC). The COVID-19 pandemic, nevertheless, was an example of the escalated situation in terms of worldwide desperate need for fast, specific and reliable home test PoC devices for the timely screening of huge numbers of people to restrict the disease from further spread. This need spawned a wave of innovative approaches for early detection of COVID-19 antibodies in human swab or blood amongst which the FET biosensing gained much more attention due to their extraordinary LoD down to femtomolar (fM) with the comparatively faster response time. As the FET sensors are promising novel PoC devices with application in early diagnosis of various diseases and especially infectious diseases, in this research, we have reviewed the recent progress on developing FET sensors for infectious diseases diagnosis accompanied with a thorough discussion on the structure of Chem/BioFET sensors and the readout circuitry for output signal processing. This approach would help engineers and biologists to gain enough knowledge to initiate their design for accelerated innovations in response to the need for more efficient management of infectious diseases like COVID-19.

COVID-19 Diagnostic Strategies Part II: Protein-Based Technologies.

After the initiation of the current outbreak, humans' lives have been profoundly impacted by COVID-19. During the first months, no rapid and reliable detecting tool was readily available to sufficiently respond to the requirement of massive testing. In this situation, when the development of an effective vaccine requires at least a few months, it is crucial to be prepared by developing and commercializing affordable, accurate, rapid and adaptable biosensors not only to fight Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) but also to be armed to avoid the pandemic in the earliest stages in the future. The COVID-19 diagnostic tools are categorized into two main groups of Nucleic Acid (NA)-based and protein-based tests. To date, nucleic acid-based detection has been announced as the gold-standard strategy for coronavirus detection; however, protein-based tests are promising alternatives for rapid and large-scale screening of susceptible groups. In this review, we discuss the current protein-based biosensing tools, the research advances and the potential protein-detecting strategies for COVID-19 detection. This narrative review aims to highlight the importance of the diagnostic tests, encourage the academic research groups and the companies to eliminate the shortcomings of the current techniques and step forward to mass-producing reliable point-of-care (POC) and point-of-need (PON) adaptable diagnostic tools for large-scale screening in the future outbreaks.

Wide Input Dynamic Range Fully Integrated Capacitive Sensor for Life Science Applications.

This paper presents a new fully integrated CMOS capacitance sensor chip with a wider input dynamic range (IDR) compared to the state-of-the-art, suitable for a variety of life science applications. With the novel differential capacitance to current conversion topology, it achieves an IDR of about seven times higher compared to the previous charge based capacitive measurement (CBCM) circuits and about three times higher compared to the CBCM with cascode current mirrors. It also features a calibration circuitry consisting of an array of switched capacitors, interdigitated electrodes (IDEs) realized on the topmost metal layer, a current-controlled 300 MHz oscillator, and a counter-serializer to create digital output. The proposed sensor, fabricated in AMS 0.35 µm CMOS technology, enables a high-resolution measurement, equal to 416 aF, of physiochemical changes in the IDE with up to 1.27 pF input offset adjustment range (IOAR). With a measurement speed of 15 µs, this sensor is among the fast CMOS capacitive sensors in the literature. In this paper, we demonstrate its functionality and applicability and present the experimental results for monitoring 2 µL evaporating droplets of chemical solvents. By using samples of solvents with different conductivity and relative permittivity, a wide range of capacitance and resistance variations in the sample-IDE interface electric equivalent model can be created. In addition, the evaporating droplet test has inherently fast dynamic changes. Based on the results, our proposed device addresses the challenge of detecting small capacitance changes despite large parasitic elements caused by the ions in the solution or by remnants deposited on the electrode.

COVID-19 Diagnostic Strategies. Part I: Nucleic Acid-Based Technologies.

The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused respiratory infection, resulting in more than two million deaths globally and hospitalizing thousands of people by March 2021. A considerable percentage of the SARS-CoV-2 positive patients are asymptomatic or pre-symptomatic carriers, facilitating the viral spread in the community by their social activities. Hence, it is critical to have access to commercialized diagnostic tests to detect the infection in the earliest stages, monitor the disease, and follow up the patients. Various technologies have been proposed to develop more promising assays and move toward the mass production of fast, reliable, cost-effective, and portable PoC diagnostic tests for COVID-19 detection. Not only COVID-19 but also many other pathogens will be able to spread and attach to human bodies in the future. These technologies enable the fast identification of high-risk individuals during future hazards to support the public in such outbreaks. This paper provides a comprehensive review of current technologies, the progress in the development of molecular diagnostic tests, and the potential strategies to facilitate innovative developments in unprecedented pandemics.

Portable Sensing Devices for Detection of COVID-19: A Review.

The coronavirus pandemic is the most challenging incident that people have faced in recent years. Despite the time-consuming and expensive conventional methods, point-of-care diagnostics have a crucial role in deterrence, timely detection, and intensive care of the disease's progress. Hence, this detrimental health emergency persuaded researchers to accelerate the development of highly-scalable diagnostic devices to control the propagation of the virus even in the least developed countries. The strategies exploited for detecting COVID-19 stem from the already designed systems for studying other maladies, particularly viral infections. The present report reviews not only the novel advances in portable diagnostic devices for recognizing COVID-19, but also the previously existing biosensors for detecting other viruses. It discusses their adaptability for identifying surface proteins, whole viruses, viral genomes, host antibodies, and other biomarkers in biological samples. The prominence of different types of biosensors such as electrochemical, optical, and electrical for detecting low viral loads have been underlined. Thus, it is anticipated that this review will assist scientists who have embarked on a competition to come up with more efficient and marketable in-situ test kits for identifying the infection even in its incubation time without sample pretreatment. Finally, a conclusion is provided to highlight the importance of such an approach for monitoring people to combat the spread of such contagious diseases.

Applications of CMOS Devices for the Diagnosis and Control of Infectious Diseases.

Emerging infectious diseases such as coronavirus disease of 2019 (COVID-19), Ebola, influenza A, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) in recent years have threatened the health and security of the global community as one of the greatest factors of mortality in the world. Accurate and immediate diagnosis of infectious agents and symptoms is a key to control the outbreak of these diseases. Rapid advances in complementary metal-oxide-semiconductor (CMOS) technology offers great advantages like high accuracy, high throughput and rapid measurements in biomedical research and disease diagnosis. These features as well as low cost, low power and scalability of CMOS technology can pave the way for the development of powerful devices such as point-of-care (PoC) systems, lab-on-chip (LoC) platforms and symptom screening devices for accurate and timely diagnosis of infectious diseases. This paper is an overview of different CMOS-based devices such as optical, electrochemical, magnetic and mechanical sensors developed by researchers to mitigate the problems associated with these diseases.

5-Axis CNC Micromilling for Rapid, Cheap, and Background-Free NMR Microcoils.

The superior mass sensitivity of microcoil technology in nuclear magnetic resonance (NMR) spectroscopy provides potential for the analysis of extremely small-mass-limited samples such as eggs, cells, and tiny organisms. For optimal performance and efficiency, the size of the microcoil should be tailored to the size of the mass-limited sample of interest, which can be costly as mass-limited samples come in many shapes and sizes. Therefore, rapid and economic microcoil production methods are needed. One method with great potential is 5-axis computer numerical control (CNC) micromilling, commonly used in the jewelry industry. Most CNC milling machines are designed to process larger objects and commonly have a precision of >25 µm (making the machining of common spiral microcoils, for example, impossible). Here, a 5-axis MiRA6 CNC milling machine, specifically designed for the jewelry industry, with a 0.3 µm precision was used to produce working planar microcoils, microstrips, and novel microsensor designs, with some tested on the NMR in less than 24 h after the start of the design process. Sample wells could be built into the microsensor and could be machined at the same time as the sensors themselves, in some cases leaving a sheet of Teflon as thin as 10 µm between the sample and the sensor. This provides the freedom to produce a wide array of designs and demonstrates 5-axis CNC micromilling as a versatile tool for the rapid prototyping of NMR microsensors. This approach allowed the experimental optimization of a prototype microstrip for the analysis of two intact adult Daphnia magna organisms. In addition, a 3D volume slotted-tube resonator was produced that allowed for 2D 1H-13C NMR of D. magna neonates and exhibited 1H sensitivity (nLODω600 = 1.49 nmol s1/2) close to that of double strip lines, which themselves offer the best compromise between concentration and mass sensitivity published to date.