Diagnostics of Tuberculosis with Single-Walled Carbon Nanotube-Based Field-Effect Transistors.

Tuberculosis (TB) is still threatening millions of people's lives, especially in developing countries. One of the major factors contributing to the ongoing epidemic of TB is the lack of a fast, efficient, and inexpensive diagnostic strategy. In this work, we developed a semiconducting single-walled carbon nanotube (SWCNT)-based field-effect transistor (FET) device functionalized with anti-Mycobacterium tuberculosis antigen 85B antibody (Ab85B) to detect the major M. tuberculosis-secreted antigen 85B (Ag85B). Through optimizing the device fabrication process by evaluating the mass of the antibody and the concentration of the gating electrolyte, our Ab85B-SWCNT FET devices achieved the detection of the Ag85B spiked in phosphate-buffered saline (calibration samples) with a limit of detection (LOD) of 0.05 fg/mL. This SWCNT FET biosensor also showed good sensing performance in biological matrices including artificial sputum and can identify Ag85B in serum after introducing bovine serum albumin (BSA) into the blocking layer. Furthermore, our BSA-blocked Ab85B-SWCNT FET devices can distinguish between TB-positive and -negative clinical samples, promising the application of SWCNT FET devices in point-of-care TB diagnostics. Moreover, the robustness of this SWCNT-based biosensor to the TB diagnosis in blood serum was enhanced by blocking SWCNT devices directly with a glutaraldehyde cross-linked BSA layer, enabling future applications of these SWCNT-based biosensors in clinical testing.

Size-Based Norfentanyl Detection with SWCNT@UiO-MOF Composites.

Single-walled carbon nanotube (SWCNT)@metal-organic framework (MOF) field-effect transistor (FET) sensors generate a signal through analytes restricting ion diffusion around the SWCNT surface. Four composites made up of SWCNTs and UiO-66, UiO-66-NH2, UiO-67, and UiO-67-CH3 were synthesized to explore the detection of norfentanyl (NF) using SWCNT@MOF FET sensors with different pore sizes. Liquid-gated FET devices of SWCNT@UiO-67 showed the highest sensing response toward NF, whereas SWCNT@UiO-66 and SWCNT@UiO-66-NH2 devices showed no sensitivity improvement compared to bare SWCNT. Comparing SWCNT@UiO-67 and SWCNT@UiO-67-CH3 indicated that the sensing response is modulated by not only the size-matching between NF and MOF channel but also NF diffusion within the MOF channel. Additionally, other drug metabolites, including norhydrocodone (NH), benzoylecgonine (BZ), and normorphine (NM) were tested with the SWCNT@UiO-67 sensor. The sensor was not responding toward NH and or BZ but a similar sensing result toward NM because NM has a similar size to NF. The SWCNT@MOF FET sensor can avoid interference from bigger molecules but sensor arrays with different pore sizes and chemistries are needed to improve the specificity.

An Ultrasensitive Norfentanyl Sensor Based on a Carbon Nanotube-Based Field-Effect Transistor for the Detection of Fentanyl Exposure.

The opioid crisis is a worldwide public health crisis that has affected millions of people. In recent years, synthetic opioids, primarily illicit fentanyl, have become the primary driver of overdose deaths. There is a great need for a highly sensitive, portable, and inexpensive analytical tool that can quickly indicate the presence and relative threat of fentanyl. In this work, we develop a semiconductor enriched (sc-) single-walled carbon nanotube (SWCNT)-based field-effect transistor (FET) biosensor functionalized with norfentanyl antibodies for the sensitive detection of norfentanyl, the primary inactive metabolite of fentanyl, in urine samples. Different sensor configurations were explored in order to obtain the most optimized sensing results. Moreover, by employing the "reduced" antibody, we achieved orientated immobilization of the norfentanyl antibody and thus brought the antigen-antibody interaction closer to the sensor surface, further improving the sensitivity. The reported norfentanyl biosensors have a limit of detection in the fg/mL region in both calibration samples and synthetic urine samples, showing ultrasensitivity and high reliability.

Cerebrospinal Fluid Leak Detection with a Carbon Nanotube-Based Field-Effect Transistor Biosensing Platform.

Cerebrospinal fluid (CSF) leakage may lead to life-threatening complications if not detected promptly. However, gel electrophoresis, the gold-standard test for confirming CSF leakage by detecting beta2-transferrin (ß2-Tf), requires 3-6 h and is labor-intensive. We developed a new ß2-Tf detection platform for rapid identification of CSF leakage. The three-step design, which includes two steps of affinity chromatography and a rapid sensing step using a semiconductor-enriched single-walled carbon nanotube field-effect transistor (FET) sensor, circumvented the lack of selectivity that antitransferrin antibody exhibits for transferrin isoforms and markedly shortened the detection time. Furthermore, three different sensing configurations for the FET sensor were investigated for obtaining the optimal ß2-Tf sensing results. Finally, body fluid (CSF and serum) tests employing our three-step strategy demonstrated high sensitivity, suggesting its potential to be used as a rapid diagnostic tool for CSF leakage.

Size Discrimination of Carbohydrates via Conductive Carbon Nanotube@Metal Organic Framework Composites.

Traditional chemical sensing methodologies have typically relied on the specific chemistry of the analyte for detection. Modifications to the local environment surrounding the sensor represent an alternative pathway to impart selective differentiation. Here, we present the hybridization of a 2-D metal organic framework (Cu3(HHTP)2) with single-walled carbon nanotubes (SWCNTs) as a methodology for size discrimination of carbohydrates. Synthesis and the resulting conductive performance are modulated by both mass loading of SWCNTs and their relative oxidation. Liquid gated field-effect transistor (FET) devices demonstrate improved on/off characteristics and differentiation of carbohydrates based on molecular size. Glucose molecule detection is limited to the single micromolar concentration range. Molecular Dynamics (MD) calculations on model systems revealed decreases in ion diffusivity in the presence of different sugars as well as packing differences based on the size of a given carbohydrate molecule. The proposed sensing mechanism is a reduction in gate capacitance initiated by the filling of the pores with carbohydrate molecules. Restricting diffusion around a sensor in combination with FET measurements represents a new type of sensing mechanism for chemically similar analytes.

Heterogeneous Growth of UiO-66-NH2 on Oxidized Single-Walled Carbon Nanotubes to Form "Beads-on-a-String" Composites.

In this work, we demonstrate a facile synthesis of UiO-66-NH2 metal-organic framework (MOF)/oxidized single-walled carbon nanotubes (ox-SWCNTs) composite at room temperature. Acetic acid (HAc) was used as a modulator to manipulate the morphology of the MOF in these composites. With a zirconium oxide cluster (Zr) to 2-aminoteraphthalate linker (ATA) 1:1.42 ratio and acetic acid modulator, we achieved predominately heterogeneous MOF growth on the sidewalls of CNTs. Understanding the growth mechanism of these composites was facilitated by conducting DFT calculations to investigate the interactions between ox-SWCNTs and the MOF precursors. The synthesized composites combine both microporosity of the MOF and electrical conductivity of the SWCNTs. Gas sensing tests demonstrated higher response for UiO-66-NH2/ox-SWCNT hybrid toward dry air saturated with dimethyl methylphosphonate (DMMP) vapor compared to oxidized single-walled carbon nanotubes (ox-SWCNTs) alone.

Growth of ZIF-8 on molecularly ordered 2-methylimidazole/single-walled carbon nanotubes to form highly porous, electrically conductive composites.

The combination of porosity and electrical conductivity in a single nanomaterial is important for a variety of applications. In this work, we demonstrate the growth of ZIF-8 on the surface of single-walled carbon nanotubes (SWCNTs). The growth mechanism was investigated and a molecularly ordered imidazole solvation layer was found to disperse SWCNTs and promote crystal growth on the sidewalls. The resultant ZIF-8/SWCNT composite demonstrates high microporosity and electrical conductivity. The ZIF-8/SWCNT composite displayed semiconducting electrical behavior and an increase in sensor sensitivity toward ethanol vapors versus pristine SWCNTs.

Osmosis-Driven Motion-Type Modulation of Biological Nanopores for Parallel Optical Nucleic Acid Sensing.

Recent developments in nanopore sequencing have inspired new concepts in precision medicine but limited in throughput. By optically encoding calcium flux from an array of nanopores, parallel measurements from hundreds of nanopores were reported, while lateral drifts of biological nanopores set obstacles for signal processing. In this paper, optical single-channel recording (oSCR) serves to track nanopores with high precision and a general principle of nanopore motion kinetics is quantitatively investigated. By finely adjusting the osmosis-oriented interactions between the lipid/substrate interfaces, motions of nanopores could be controllably restricted. Improved signal-to-noise ratio is observed from motion-restricted nanopores, which is experimentally demonstrated. To systematically evaluate oSCR with asymmetric salt concentrations, a finite element method simulation is established. oSCR with an array of immobilized nanopores suggests new strategies for sequencing DNA by microscopic imaging in high throughput and is widely applicable to the investigation of other transmembrane proteins.