Highly Effective and Efficient Self-Assembled Multilayer-Based Electrode Passivation for Operationally Stable and Reproducible Electrolyte-Gated Transistor Biosensors.

To ensure the operational stability of transistor-based biosensors in aqueous electrolytes during multiple measurements, effective electrode passivation is crucially important for reliable and reproducible device performances. This paper presents a highly effective and efficient electrode passivation method using a facile solution-processed self-assembled multilayer (SAML) with excellent insulation property to achieve operational stability and reproducibility of electrolyte-gated transistor (EGT) biosensors. The SAML is created by the consecutive self-assembly of three different molecular layers of 1,10-decanedithiol, vinyl-polyhedral oligomeric silsesquioxane, and 1-octadecanethiol. This passivation enables EGT to operate stably in phosphate-buffered saline (PBS) during repeated measurements over multiple cycles without short-circuiting. The SAML-passivated EGT biosensor is fabricated with a solution-processed In2O3 thin film as an amorphous oxide semiconductor working both as a semiconducting channel in the transistor and as a functionalizable biological interface for a bioreceptor. The SAML-passivated EGT including In2O3 thin film is demonstrated for the detection of Tau protein as a biomarker of Alzheimer's disease while employing a Tau-specific DNA aptamer as a bioreceptor and a PBS solution with a low ionic strength to diminish the charge-screening (Debye length) effect. The SAML-passivated EGT biosensor functionalized with the Tau-specific DNA aptamer exhibits ultrasensitive, quantitative, and reliable detection of Tau protein from 1 × 10-15 to 1 × 10-10 M, covering a much larger range than clinical needs, via changes in different transistor parameters. Therefore, the SAML-based passivation method can be effectively and efficiently utilized for operationally stable and reproducible transistor-based biosensors. Furthermore, this presented strategy can be extensively adapted for advanced biomedical devices and bioelectronics in aqueous or physiological environments.

Single-Nanoparticle-Based Digital SERS Sensing Platform for the Accurate Quantitative Detection of SARS-CoV-2.

To prevent the ongoing spread of the highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), accurate and early detection based on a rapid, ultrasensitive, and highly reliable sensing method is crucially important. Here, we present a bumpy core-shell surface-enhanced Raman spectroscopy (SERS) nanoprobe-based sensing platform with single-nanoparticle (SNP)-based digital SERS analysis. The tailorable bumpy core-shell SERS nanoprobe with an internal self-assembled monolayer of 4-nitrobenzenethiol Raman reporters, synthesized using HEPES biological buffer, generates a strong, uniform, and reproducible SERS signal with an SNP-level sensitive and narrowly distributed enhancement factor (2.1 × 108 to 2.2 × 109). We also propose an SNP-based digital SERS analysis method that provides direct visualization of SNP detection at ultralow concentrations and reliable quantification over a wide range of concentrations. The bumpy core-shell SERS nanoprobe-based sensing platform with SNP-based digital SERS analysis achieves the ultrasensitive and quantitative detection of the SARS-CoV-2 spike protein with a limit of detection of 7.1 × 10-16 M over a wide dynamic range from 3.7 × 10-15 to 3.7 × 10-8 M, far outperforming the conventional enzyme-linked immunosorbent assay method for the target protein. Furthermore, it can detect mutated spike proteins from the SARS-CoV-2 variants, representing the key mutations of Alpha, Beta, Gamma, Delta, and Omicron variants. Therefore, this sensing platform can be effectively and efficiently used for the accurate and early detection of SARS-CoV-2 and be adapted for the ultrasensitive and reliable detection of other highly infectious diseases.

Multi-modal liquid biopsy platform for cancer screening: screening both cancer-associated rare cells and cancer cell-derived vesicles on the fabric filters for a reliable liquid biopsy analysis.

Circulating tumor cells (CTCs) are receiving a great amount of scientific interest as a diagnostic biomarker for various types of cancer. Despite the recent progress in the development of highly sensitive CTC isolation devices, post-capture analysis of CTCs is still hindered by technical challenges associated with their rarity. Herein, we present a multi-modal CTC screening platform which is capable to analyze CTCs and CTC-derived extracellular vesicles (EVs), simultaneously from a single sample. Cytochalasin B (CB) treatment promotes cells to release large number of EVs from their surface, as demonstrated by CB-treated cells (5 µg/mL for 3 h) secreting 3.5-fold more EVs, compared to the non-treated cells. CB further generates 1.7-fold more EVs from the cells captured on our CTC filtration device (the fabric filter), compared to those from the cell culture flasks, owing to its multiple pore structure design which reduces the non-specific binding of EVs. Both CB-treated cancer cells and CB-induced EVs are found to overexpress tumor-associated markers, demonstrating a potential for the development of CTC dual-screening platform. Collectively, the results presented in this study reveal that our multi-modal cancer screening platform can synergistically improve the reliability and efficacy of the current CTC analysis systems.

Circulating tumor cells are associated with poor outcomes in early-stage hepatocellular carcinoma: a prospective study.

BACKGROUND: Previous studies evaluating association between circulating tumor cells (CTCs) and clinical outcomes in hepatocellular carcinoma (HCC) have shown inconsistent results due to suboptimal detection methods and patient heterogeneity. METHODS: Patients undergoing surgery for early-stage HCC were prospectively enrolled. The CTC numbers were determined using a tapered slit platform, which detects CTCs based on the cell size and morphology. Survival and recurrence were evaluated, and Cox proportional hazards models were used to demonstrate the prognostic significance of CTC. RESULTS: Of 105 patients, 25 had increased CTC numbers after surgery (ΔCTC > 0, defined as positive) and a significantly higher level of recurrence (p = 0.042). A positive ΔCTC was seen to be an independent predictor of recurrence (hazard ratio 2.28), along with hepatitis B virus infection, alanine aminotransferase level, and the presence of satellite nodules (all p < 0.05). Subgroup analyses showed that a positive ΔCTC was associated with lower survival and higher recurrence among patients with low alpha-fetoprotein levels and cirrhosis (all p < 0.05). CONCLUSION: Calculation of ΔCTC based on the physical properties of the cells is predictive of recurrence in patients with early HCC undergoing surgery.

Turtle mimetic soft robot with two swimming gaits.

This paper presents a biomimetic turtle flipper actuator consisting of a shape memory alloy composite structure for implementation in a turtle-inspired autonomous underwater vehicle. Based on the analysis of the Chelonia mydas, the flipper actuator was divided into three segments containing a scaffold structure fabricated using a 3D printer. According to the filament stacking sequence of the scaffold structure in the actuator, different actuating motions can be realized and three different types of scaffold structures were proposed to replicate the motion of the different segments of the flipper of the Chelonia mydas. This flipper actuator can mimic the continuous deformation of the forelimb of Chelonia mydas which could not be realized in previous motor based robot. This actuator can also produce two distinct motions that correspond to the two different swimming gaits of the Chelonia mydas, which are the routine and vigorous swimming gaits, by changing the applied current sequence of the SMA wires embedded in the flipper actuator. The generated thrust and the swimming efficiency in each swimming gait of the flipper actuator were measured and the results show that the vigorous gait has a higher thrust but a relatively lower swimming efficiency than the routine gait. The flipper actuator was implemented in a biomimetic turtle robot, and its average swimming speed in the routine and vigorous gaits were measured with the vigorous gait being capable of reaching a maximum speed of 11.5 mm s(-1).