An Ultrasensitive Biomimetic Optic Afferent Nervous System with Circadian Learnability.

The optic afferent nervous system (OANS) plays a significant role in generating vision and circadian behaviors based on light detection and signals from the endocrine system. However, the bionic simulation of this photochemically mediated behavior is still a challenge for neuromorphic devices. Herein, stimuli of neurotransmitters at ultralow concentrations and illumination are coupled to artificial synapses with the aid of biofunctionalized heterojunction and tunneling to successfully simulate a circadian neural response. Furthermore, the mechanisms underlying the photosensitive synaptic current in response to stimuli are described. Interestingly, this OANS is demonstrated to be capable of mimicking normal and abnormal circadian learnability by combining the measured synaptic current with a three-layer spike neural network. Strong theoretical and experimental evidence, as well as applications, are provided for the proposed biomimetic OANS to demonstrate that it can reproduce biological circadian behavior, thus establishing it as a promising candidate for future neuromorphic intelligent robots.

Fibrous MXene Synapse-Based Biomimetic Tactile Nervous System for Multimodal Perception and Memory.

Biomimetic tactile nervous system (BTNS) inspired by organisms has motivated extensive attention in wearable fields due to its biological similarity, low power consumption, and perception-memory integration. Though many works about planar-shape BTNS are developed, few researches could be found in the field of fibrous BTNS (FBTNS) which is superior in terms of strong flexibility, weavability, and high-density integration. Herein, a FBTNS with multimodal sensibility and memory is proposed, by fusing the fibrous poly lactic acid (PLA)/Ag/MXene/Pt artificial synapse and MXene/EMIMBF4 ionic conductive elastomer. The proposed FBTNS can successfully perceive external stimuli and generate synaptic responses. It also exhibits a short response time (23 ms) and low set power consumption (17 nW). Additionally, the proposed device demonstrates outstanding synaptic plasticity under both mechanical and electrical stimuli, which can simulate the memory function. Simultaneously, the fibrous devices are embedded into textiles to construct tactile arrays, by which biomimetic tactile perception and temporary memory functions are successfully implemented. This work demonstrates the as-prepared FBTNS can generate biomimetic synaptic signals to serve as artificial feeling signals, it is thought that it could offer a fabric electronic unit integrating with perception and memory for Human-Computer interaction, and has great potential to build lightweight and comfortable Brain-Computer interfaces.

Near-Infrared data classification at phone terminal based on the combination of PCA and CS-RBFSVC algorithms.

Near-infrared (NIR) spectroscopy is a non-destructive, efficient and convenient detection technology, with the emergence of portable NIR spectrometers, NIR mobile applications (APPs) come into being. The popularity of intelligent mobile phones provides an impetus to the research and development of NIR APPs, however, the primary functions such as operating the NIR spectrometers and collecting data cannot satisfy NIR users in the field of data processing. Herein, we propose an APP processing NIR data locally at the mobile terminal, by the comprehensive utilization of Principal Component Analysis (PCA) and Cuckoo Search algorithm optimized Support Vector Classifier with radial basis function (RBFSVC) kernel (CS-RBFSVC). 738 NIR samples of four drugs (Cydiodine Buccal Tablets, Sulfasalazine Enteric-coated Tablets, Dexamethasone Acetate Tablets, Vecuronium Bromide for Injection) were used as the validation objects to train and test the data classification model. Firstly, the original data were subjected to dimensional reduction through PCA for the purpose of compressing calculation amount. Secondly, the CS-RBFSVC model was utilized to classify the types of drugs and their manufacturers, moreover, the improved accuracy and efficiency by introducing Cuckoo Search (CS) algorithm into RBFSVC were proven in comparison with the conventional grid optimized RBFSVC (Grid-RBFSVC) and Linear Support Vector Classifier (Linear-SVC). Last but not least, an APP based on the proposed PCA and CS-RBFSVC model is developed and demonstrated to be able to classify the type of drugs with an accuracy of 100%, the accuracies of classifying the drugs' manufacturers were 100%, 100%, 98.3% and 90.7%, respectively. Conclusively, the proposed PCA and CS-RBFSVC based model can provide a low-consumption, high accuracy and quick strategy for NIR data classification and overcome the limitations of internal storage and operating speed at phone terminals, in conjunction with the portable NIR spectrometer, it is believed to push forward NIR technology into the instant detection and on-site inspection.

Electrolyte-Gated Graphene Field Effect Transistor-Based Ca2+ Detection Aided by Machine Learning.

Flexible electrolyte-gated graphene field effect transistors (Eg-GFETs) are widely developed as sensors because of fast response, versatility and low-cost. However, their sensitivities and responding ranges are often altered by different gate voltages. These bias-voltage-induced uncertainties are an obstacle in the development of Eg-GFETs. To shield from this risk, a machine-learning-algorithm-based LgGFETs' data analyzing method is studied in this work by using Ca2+ detection as a proof-of-concept. For the as-prepared Eg-GFET-Ca2+ sensors, their transfer and output features are first measured. Then, eight regression models are trained with the use of different machine learning algorithms, including linear regression, support vector machine, decision tree and random forest, etc. Then, the optimized model is obtained with the random-forest-method-treated transfer curves. Finally, the proposed method is applied to determine Ca2+ concentration in a calibration-free way, and it is found that the relation between the estimated and real Ca2+ concentrations is close-to y = x. Accordingly, we think the proposed method may not only provide an accurate result but also simplify the traditional calibration step in using Eg-GFET sensors.

A Disposable Printed Liquid Gate Graphene Field Effect Transistor for a Salivary Cortisol Test.

Circadian rhythm of salivary cortisol is of clinical significance, tracking salivary cortisol in domicile is welcomed by both doctor and patient, due to its merits of noninvasion, ease of sampling, and free-of-stress response. Here, we present a portable salivary cortisol test setup based on a liquid gate graphene field effect transistor (Lg-GFET) for the first time. In this work, the Lg-GFET was prepared by the printing technology and exploited as a sensitive material. In the procedures of device preparation, the modified liquid exfoliation method and direct-ink-write technology were utilized for synthesizing the graphene ink and printing Lg-GFETs; then, the as-prepared Lg-GFETs were decorated and functionalized by tetrakis(4-carboxyphenyl) porphyrin and the cortisol aptamer, successively. Their sensitivity, selectivity, and robustness are seriously examined. The test results indicate that the sensors have good linear sensitivities over a seven-log analyte concentration range (0.01 to 104 nM) and the anti-interference ability to distinguish from the substancess with similar chemical structures. Moreover, the conceptual application for tracking circadian rhythm was carried out successfully. Conclusively, the proposed flexible Lg-GFET-based salivary cortisol detection platform can satisfy the requirements of the salivary cortisol's assay for instant detection. Additionally, it also provides an alternative solution for developing similar household medical appliances.

Possibility of Combining Carbon Dots and Liquid Exfoliated Graphene as a Carbon-Based Light Addressable Potentiometric Sensor.

A light addressable potentiometric sensor (LAPS) is a versatile sensing platform for bioassay. However, the lack of carbon-based LAPS (C-LAPS) is a bottleneck for its sustainable development in a carbon electronic era. Herein, a study of C-LAPS based on the combinations of carbon dots (CDs) and liquid exfoliated graphene (LEG) is presented. Devices of C-LAPS are first fabricated by self-assembling the hydrothermally synthesized CDs and the cosolvent ultrasonic delaminated LEG on poly(diallyldimethylammonium chloride) (PDDA)-modified indium tin oxide (ITO) glasses. According to the stacking orders of CDs and LEG, C-LAPS are named as CDs/LEG@PDDA/ITO and LEG/CDs@PDDA/ITO. Then, their electronic and photoelectronic features are measured and compared with the pure CD- and pure LEG-decorated ITO electrodes. Furthermore, working mechanisms are proposed by means of the classical theories of energy band bending and built-in electric field at the heterojunction of CDs and LEG. The resemblances of CDs/LEG@PDDA/ITO-based C-LAPS with Si-based LAPS (Si-LAPS) are confirmed from the points of view of production and separation of the photogenerated carriers, the formation of photocurrent, and the distinction with LEG/CDs@PDDA/ITO. Finally, its feasibility for biological application is justified by using the immune reaction of 5-methylcytosine (5mC) and its antibody (anti-5mC) as a proof of concept. The improved linear responses are evidenced by the comparisons with Si-LAPS' results. Conclusively, the proposed C-LAPS is believed to be a candidate for traditional semiconductor-based LAPS, with the merit of solution-processable. Meanwhile, the theoretical deductions about C-LAPS' principle can also pave the way for developing similar carbon-based sensors.

Astrocytic glutamate transporter 1 (GLT1) deficient mice exhibit repetitive behaviors.

Glutamatergic dysregulation is known to contribute to obsessive-compulsive disorder (OCD). Astrocytic glutamate transporter 1 (GLT1) is responsible for the majority of glutamate clearance. However, the role of GLT1 in OCD-like behavior remains unclear. Here, we found that astrocytic GLT1 deficient mice showed increased wheel running activity but reduced home cage activity. Notably, they exhibited elevated grooming/rearing time and increased repetitive behavior counts in contextual and cued fear conditioning. In addition, they showed increased rearing counts in the metabolic chamber, and also augmented rearing time and jumping counts in the open field test. Taken together, our findings suggest that astrocytic GLT1 deficiency promotes OCD-like repetitive behaviors.

TBK1 regulates regeneration of pancreatic ß-cells.

Small-molecule inhibitors of non-canonical IκB kinases TANK-binding kinase 1 (TBK1) and IκB kinase ε (IKKε) have shown to stimulate ß-cell regeneration in multiple species. Here we demonstrate that TBK1 is predominantly expressed in ß-cells in mammalian islets. Proteomic and transcriptome analyses revealed that genetic silencing of TBK1 increased expression of proteins and genes essential for cell proliferation in INS-1 832/13 rat ß-cells. Conversely, TBK1 overexpression decreased sensitivity of ß-cells to the elevation of cyclic AMP (cAMP) levels and reduced proliferation of ß-cells in a manner dependent on the activity of cAMP-hydrolyzing phosphodiesterase 3 (PDE3). While the mitogenic effect of (E)3-(3-phenylbenzo[c]isoxazol-5-yl)acrylic acid (PIAA) is derived from inhibition of TBK1, PIAA augmented glucose-stimulated insulin secretion (GSIS) and expression of ß-cell differentiation and proliferation markers in human embryonic stem cell (hESC)-derived ß-cells and human islets. TBK1 expression was increased in ß-cells upon diabetogenic insults, including in human type 2 diabetic islets. PIAA enhanced expression of cell cycle control molecules and ß-cell differentiation markers upon diabetogenic challenges, and accelerated restoration of functional ß-cells in streptozotocin (STZ)-induced diabetic mice. Altogether, these data suggest the critical function of TBK1 as a ß-cell autonomous replication barrier and present PIAA as a valid therapeutic strategy augmenting functional ß-cells.

Multiprobe Assay for Clinical SEPT9 Methylation Based on the Carbon Dot-Modified Liquid-Exfoliated Graphene Field Effect Transistor with a Potential to Present a Methylation Panorama.

The hypermethylation in the promoter region of the SEPT9 gene is associated with the development of colorectal cancer (CRC). Although its clinical significance for early diagnosis and screening of CRC has been demonstrated, the tedious operations in the conventional DNA methylation (DNAm) detection hinder its wide application. Herein, an electronic method for determining SEPT9 methylation in CRC patients is proposed by using the carbon dot-modified liquid exfoliated graphene field effect transistor (CDs-LEG-FET) as the DNAm sensor, the specifically designed probes to capture the SEPT9 gene and the immunologic recognition to recognize 5-methylcytosine (5mC) positions on the anchored sequences. The identification and nanomorphology of the as-prepared materials and devices are executed first by the characterizations of UV-vis, Raman, atomic force microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and electronic measurements. Then, the role of CDs in enhancing DNAm sensitivity of CD-LEG-FET is manifested by comparing it with that of CD-free LEG-FET. Third, the captured SEPT9 genes on CD-LEG-FETs by different probes are evaluated, and the optimized temperature for hybridizing the target ssDNA sequences is determined to be 48 °C. Furthermore, the detection sensitivity for the low-quantity of DNA samples is demonstrated to be as low as 2 ng. Finally, the methylation degree of the tumor and corresponding noncancerous tissue DNA samples were examined by the proposed electric method and methylight assay in parallel. The diagnostic value of the electrical assay is confirmed by using the receiver operating characteristic curves; meanwhile, the superiority of the CD-LEG-FET platform is found to present a methylation panorama of the target gene.

Porous Graphene Oxide Decorated Ion Selective Electrode for Observing Across-Cytomembrane Ion Transport.

The technology for measuring cytomembrane ion transport is one of the necessities in modern biomedical research due to its significance in the cellular physiology, the requirements for the non-invasive and easy-to-operate devices have driven lots of efforts to explore the potential electrochemical sensors. Herein, we would like to evidence the exploitation of the porous graphene oxide (PGO) decorated ion selective electrode (ISE) as a detector to capture the signal of cytomembrane ion transport. The tumor cells (MDAMB231, A549 and HeLa) treated by iodide uptake operation, with and without the sodium-iodide-symporter (NIS) expression, are used as proofs of concept. It is found that under the same optimized experimental conditions, the changed output voltages of ISEs before and after the cells' immobilization are in close relation with the NIS related ion's across-membrane transportation, including I-, Na+ and Cl-. The explanation for the measured results is proposed by clarifying the function of the PGO scaffold interfacial micro-environment (IME), that is, in this spongy-like micro-space, the NIS related minor ionic fluctuations can be accumulated and amplified for ISE to probe. In conclusion, we believe the integration of the microporous graphene derivatives-based IME and ISE may pave a new way for observing the cytomembrane ionic activities.

Astrocytic Glutamate Transporter 1 (GLT1) Deficiency Reduces Anxiety- and Depression-Like Behaviors in Mice.

Glutamatergic dysregulation is known to contribute to altered emotional regulation. Astrocytic glutamate transporter 1 (GLT1) is responsible for the majority of glutamate clearance from synapse. However, the role of astrocytic GLT1 in affective processes such as anxiety- and depression-like behavior is not fully understood. Here, we found that astrocytic GLT1 deficient mice entered more frequently, and spent more time in the open arms of elevated plus maze without difference in overall distance traveled in the open field, nor were there any metabolic changes observed in the metabolic chamber compared to wildtype mice. Moreover, mice lacking astrocytic GLT1 exhibited less immobile time and moved greater area in the tail suspension test. Similarly, in the forced swim test, they showed less immobile time and moved greater area. In addition, we found that astrocytic GLT1 deficiency reduced freezing responses in the fear contextual and cued tests. Taken together, our findings suggest that astrocytic GLT1 deficiency decreases anxiety and depression-like behaviors.

Type 1 equilibrative nucleoside transporter (ENT1) regulates sex-specific ethanol drinking during disruption of circadian rhythms.

Disruptions in circadian rhythms are risk factors for excessive alcohol drinking. The ethanol-sensitive adenosine equilibrative nucleoside transporter type 1 (ENT1, slc29a1) regulates ethanol-related behaviors, sleep, and entrainment of circadian rhythms. However, the mechanism underlying the increased ethanol consumption in ENT1 knockout (KO) mice in constant light (LL) and whether there are sex differences in ethanol consumption in ENT1 mice are less studied. Here, we investigated the effects of loss of ENT1, LL, and sex on ethanol drinking using two-bottle choice. In addition, we monitored the locomotor activity rhythms. We found that LL increased ethanol drinking and reduced accumbal ENT1 expression and adenosine levels in male but not female mice, compared with control mice. Interestingly, only LL-exposed male, not female, ENT1 KO mice exhibited higher ethanol drinking and a longer circadian period with a higher amplitude compared with wild-type (WT) mice. Furthermore, viral-mediated rescue of ENT1 expression in the NAc of ENT1 KO mice reduced ethanol drinking, demonstrating a possible causal link between ENT1 expression and ethanol drinking in males. Together, our findings indicate that deficiency of ENT1 expression contributes to excessive ethanol drinking in a sex-dependent manner.

Publisher Correction: Inhibition of TBK1/IKKε Promotes Regeneration of Pancreatic ß-cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Function of Tetra (4-Aminophenyl) Porphyrin in Altering the Electronic Performances of Reduced Graphene Oxide-Based Field Effect Transistor.

Porphyrin functionalized reduced graphene oxide (rGO) is attractive for multi-disciplinary research studies, and its improvements for an rGO-based field effect transistor (rGO-FET) were exploited to realize ultrasensitive biochemical and clinical assay. Although it was believed that the hybrids of porphyrin and rGO can make positive impacts on the rGO-FET's electronic performances, the understandings of its functions are still piecemeal. Herein, the reduced mixtures of tetra (4-aminophenyl) porphyrin (TAP), GO (TAP-rGO), and the FET channeled by them are examined to throw a light on the possible approaches through which TAP affects rGO's quality and its carrier mobilities. A TAP-caused game relationship is established by deliberating about the results of the intentionally altered experimental conditions, including TAP contents and the overmixing pretreatment. The p-type doping deduction for the right-shifted ambipolar transfer characteristic curves is evidenced by X-ray photoelectron spectroscopy (XPS). The problems posed by the TAP-induced FET features' improvement, regression, and deterioration are clarified by the integrated proofs from Raman fingerprints, the amide and carboxyl groups' changing trajectory found by C1s XPS core spectra, and the enlarged few-layer graphene morphology from atomic force microscope and transmission electron microscope. We hope that this effort will provide some constructive recommendations for producing low-cost graphene derivatives and promoting their applications in FET-like electronic components.

Meso-tetra(4-carboxyphenyl)porphine-Enhanced DNA Methylation Sensing Interface on a Light-Addressable Potentiometric Sensor.

DNA methylation (DNAm) sensors are an emerging branch in the discipline of sensors. It is believed to be able to promote the next generation of epigenetics-based diagnostic technology. Differing from the traditional biochemical sensors that aimed at individual molecules, the challenge in DNAm sensors is how to determine the amount of 5-methylcytosine (5mC) in a continuous nucleotide sequence. Here, we report a comparative study about meso-tetra(4-carboxyphenyl)porphine (TCPP)-based DNAm sensing interfaces on a light-addressable potentiometric sensor (LAPS), depending on TCPP's postures that are flat in the π-conjugated TCPP layer on reduced-graphene-oxide-decorated LAPS (#1) and stand-up in the covalently anchored TCPP on glutaraldehyde (GA)-treated LAPS (#2), along with the blank one (only GA-treated LAPS, #3). These DNAm sensing interfaces are also distinct from the traditional biosensing interface on LAPS, that is: it is not functionalized by the sensing indicator (5mC antibody, in this case) but by the target nucleotide sequence. The surface characterization techniques such as Raman spectra, scanning electron microscopy, and X-ray photoelectron spectroscopy are conducted to prove the decorations, as well as the anchored nucleotides. It is found that, though all of them can detect as low as one 5mC in the target sequence, the enhanced DNAm sensitivity is obtained by #2, which is evidenced by the higher output-voltage changing ratio for the 5mC site of #2 than those of #1 and #3. Furthermore, the underlying causes for the improved sensitivity in #2 are proposed, according to the conformational and electronic properties of TCPP molecules. Conclusively, TCPP's synergetic function, including the molecular configuration and the activate (carboxyl) groups on its peripheral substituents, to improve the DNAm sensing interface on LAPS is investigated and demonstrated. This can shed light on a new approach for DNA methylation detection, with the merits of low cost, independence on bisulfite conversion, and polymerase chain reaction.

Study of porphyrin-modified liquid exfoliated graphene field-effect transistors for evaluating DNA methylation degree.

The applications of graphene field-effect transistors (FETs) for monitoring DNA hybridization have been widely accepted; however, for evaluating DNA methylation degree, an emerging requirement of epigenetic research, no work has been found due to the difficulties in detecting 5-methylcytosine (5mC) sites along the genomic sequence as well as counting their amount (NmC). Herein, to achieve this, a strategy for exploiting a liquid exfoliated graphene (LEG)-based FET (LEG-FET) as a sensing platform was proposed. First, LEG-FETs were prepared and activated by tetra-4-aminophenyl-porphyrin (TAPP) for anchoring single-strand DNAs (ssDNAs). Second, the 5mC sites in ssDNA were recognized by the specifically absorbed 5mC antibody (5mCab) and transduced to the changed currents (ΔIDS) by LEG-FET according to the integration of the methylation-immuno sensing principle and FET's working mechanism. Briefly, more 5mCab molecules could be captured by more 5mC sites, resulting in larger ΔIDS. The TAPP effects on LEG-FET were analyzed by SEM, Raman, AFM, and XPS characterizations as well as electronic measurements. The validity of this LEG-FET sensing platform for evaluating DNA methylation degree was proven step by step; this included the examinations of the synthesized ssDNAs with the known NmC and real ssDNA samples, whose methylation degrees were pre-determined by the gold-standard method, which is based on tedious bisulphite sequence operations and expensive mass spectrometry technology. Moreover, theoretical explanations were also provided for the sensing mechanism in the proposed DNA methylation analytical components. In conclusion, the positive and linear relations of IDS changing ratio vs. NmC as well as the detection limit of one 5mC site indicate that TAPP-modified LEG-FET can provide an alternative analytical tool to realize fast and economical DNA methylation evaluation.

Reduced Carboxylate Graphene Oxide based Field Effect Transistor as Pb2+ Aptamer Sensor.

Aptamer functionalized graphene field effect transistor (apta-GFET) is a versatile bio-sensing platform. However, the chemical inertness of graphene is still an obstacle for its large-scale applications and commercialization. In this work, reduced carboxyl-graphene oxide (rGO-COOH) is studied as a self-activated channel material in the screen-printed apta-GFETs for the first time. Examinations are carefully executed using lead-specific-aptamer as a proof-of-concept to demonstrate its functions in accommodating aptamer bio-probes and promoting the sensing reaction. The graphene-state, few-layer nano-structure, plenty of oxygen-containing groups and enhanced LSA immobilization of the rGO-COOH channel film are evidenced by X-ray photoelectron spectroscopy, Raman spectrum, UV-visible absorbance, atomic force microscopy and scanning electron microscope. Based on these characterizations, as well as a site-binding model based on solution-gated field effect transistor (SgFET) working principle, theoretical deductions for rGO-COOH enhanced apta-GFETs' response are provided. Furthermore, detections for disturbing ions and real samples demonstrate the rGO-COOH channeled apta-GFET has a good specificity, a limit-of-detection of 0.001 ppb, and is in agreement with the conventional inductively coupled plasma mass spectrometry method. In conclusion, the careful examinations demonstrate rGO-COOH is a promising candidate as a self-activated channel material because of its merits of being independent of linking reagents, free from polymer residue and compatible with rapidly developed print-electronic technology.

Genetic variant in SLC1A2 is associated with elevated anterior cingulate cortex glutamate and lifetime history of rapid cycling.

Glutamatergic dysregulation is implicated in the neurobiology of mood disorders. This study investigated the relationship between the anterior cingulate cortex (AC) glutamate, as measured by proton magnetic resonance spectroscopy (1H-MRS), and single-nucleotide polymorphisms (SNPs) from four genes (GLUL, SLC1A3, SLC1A2, and SLC1A7) that regulate the extracellular glutamate in 26 depressed patients with major depressive disorder (MDD; n = 15) and bipolar disorder (BD; n = 11). Two SNPs (rs3812778 and rs3829280), in perfect linkage disequilibrium, in the 3' untranslated region of the EAAT2 gene SLC1A2, were associated with AC glutamate, with minor allele carriers having significantly higher glutamate levels (p < 0.001) in comparison with common allele homozygotes. In silico analysis revealed an association of minor allele carriers of rs3812778/rs382920 with an upregulation of the astrocytic marker CD44 localized downstream of SLC1A2 on chromosome 11. Finally, we tested the disease relevance of these SNPs in a large group of depressed patients [MDD (n = 458); BD (n = 1473)] and found that minor allele carriers had a significantly higher risk for rapid cycling (p = 0.006). Further work is encouraged to delineate the functional impact of excitatory amino acid transporter genetic variation on CD44 associated physiology and glutamatergic neurotransmission, specifically glutamate-glutamine cycling, and its contribution to subphenotypes of mood disorders.

Porous Graphene Oxide Enhanced Aptamer Specific Circulating-Tumor-Cell Sensing Interface on Light Addressable Potentiometric Sensor: Clinical Application and Simulation.

The circulating-tumor-cell (CTC) specific aptamer is believed to be a power recognition factor to realize clinical CTC assay. However, the limited sensing range is still one of the challenges in its real application. The porous-graphene-oxide (PGO) enhanced aptamer specific CTC sensing interface is studied on the platform of light-addressable-potentiometric-sensor (LAPS) to provide a clinical available method for CTC detection. The underlying mechanism of this sensing interface on LAPS is modeled and simulated. It is confirmed to be a promising candidate for CTC assay by the linear responding for 5-5000 spiked cells, as well as the satisfactory sensitivity for clinical samples.