Compensation for Electrode Detachment in Electrical Impedance Tomography with Wearable Textile Electrodes.

Electrical impedance tomography (EIT) is a radiation-free and noninvasive medical image reconstruction technique in which a current is injected and the reflected voltage is received through electrodes. EIT electrodes require good connection with the skin for data acquisition and image reconstruction. However, detached electrodes are a common occurrence and cause measurement errors in EIT clinical applications. To address these issues, in this study, we proposed a method for detecting faulty electrodes using the differential voltage value of the detached electrode in an EIT system. Additionally, we proposed the voltage-replace and voltage-shift methods to compensate for invalid data from the faulty electrodes. In this study, we present the simulation, experimental, and in vivo chest results of our proposed methods to verify and evaluate the feasibility of this approach.

Dry Wearable Textile Electrodes for Portable Electrical Impedance Tomography.

Electrical impedance tomography (EIT), a noninvasive and radiation-free medical imaging technique, has been used for continuous real-time regional lung aeration. However, adhesive electrodes could cause discomfort and increase the risk of skin injury during prolonged measurement. Additionally, the conductive gel between the electrodes and skin could evaporate in long-term usage and deteriorate the signal quality. To address these issues, in this work, textile electrodes integrated with a clothing belt are proposed to achieve EIT lung imaging along with a custom portable EIT system. The simulation and experimental results have verified the validity of the proposed portable EIT system. Furthermore, the imaging results of using the proposed textile electrodes were compared with commercial electrocardiogram electrodes to evaluate their performance.

Hybridization Chain Reactions Targeting the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

In this work, hybridization chain reactions (HCRs) toward Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) nucleocapsid phosphoproteins gene loci and human RNase P are proposed to provide an isothermal amplification screening tool. The proposed chain reactions target the complementary DNA (cDNA) of SARS-CoV-2, with loci corresponding to gold-standard polymerase chain reaction (PCR) loci. Four hybridization chain reaction reactions are demonstrated herein, targeting N1/N2/N3 loci and human RNase P. The design of the hybridization chain reaction, herein, is assisted with an algorithm. The algorithm helps to search target sequences with low local secondary structure and high hybridization efficiency. The loop domain of the fuel hairpin molecule H1 and H2, which are the tunable segments in such reactions, are used as an optimization parameter to improve the hybridization efficiency of the chain reaction. The algorithm-derived HCR reactions were validated with gel electrophoresis. All proposed reactions exhibit a hybridization complex with a molecular mass >1.5k base pairs, which is clear evidence of chain reaction. The hybridization efficiency trend revealed by gel electrophoresis corresponds nicely to the simulated data from the algorithm. The HCR reactions and the corresponding algorithm serve as a basis to further SARS-CoV-2 sensing applications and facilitate better screening strategies for the prevention of on-going pandemics.

Low-Fouling Characteristics of Ultrathin Zwitterionic Cysteine SAMs.

Surface fouling remains an exigent issue for many biological implants. Unwanted solutes adsorb to reduce device efficiency and hasten degradation while increasing the risks of microbial colonization and adverse inflammatory response. To address unwanted fouling in modern implants in vivo, surface modification with antifouling polymers has become indispensable. Recently, zwitterionic self-assembled monolayers, which contain two or more charged functional groups but are electrostatically neutral and form highly hydrated surfaces, have been the focus of many antifouling coatings. Reports using various compositions of zwitterionic polymer brushes have demonstrated ultralow fouling in the ng/cm2 range. These coatings, however, are thick and can hinder the target application of biological devices. Here, we report an ultrathin (8.52 Å) antifouling self-assembled monolayer composed of cysteine that is amenable to facile fabrication. The antifouling characteristics of the zwitterionic surfaces were evaluated against bovine serum albumin, fibrinogen, and human blood in real time using quartz crystal microbalance and surface plasmon resonance imaging. Compared to untreated gold surfaces, the ultrathin cysteine coating reduced the adsorption of bovine serum albumin by 95% (43 ng/cm2 adsorbed) after 3 h and 90% reduction after 24 h. Similarly, the cysteine self-assembled monolayer reduced the adsorption of fibrinogen as well as human blood by >90%. The surfaces were further characterized using scanning electron microscopy: protein-enhanced adsorption and cellular adsorption in human blood was found on untreated surfaces but not on the cysteine SAM-protected surfaces. These findings suggest that surfaces can be functionalized with an ultrathin layer of cysteine to resist the adsorption of key proteins, with performance comparable to zwitterionic polymer brushes. As such, cysteine surface coatings are a promising methodology to improve the long-term utility of biological devices.

Reversible Spasticity Suppression and Locomotion Change After Pulsed Radiofrequency on the Dorsal Root Ganglia of Rats With Spinal Cord Injury.

OBJECTIVES: Radiofrequency has been used to suppress spasticity affecting motion in patients with cerebral palsy and spinal cord injury. This study tested spasticity suppression and locomotion change after pulsed radiofrequency (PRF) at the dorsal root ganglion of rats with spasticity. MATERIALS AND METHODS: Twenty-four rats that survived for 28 days after thoracic spinal cord injury and showed spasticity in the right hind limb were separated randomly to a PRF group or Sham operation group. PRF consisted of 2 Hz biphasic 25 msec trains of PRF (500 kHz, 5 V intensity) applied on the right L5 dorsal root ganglion for 300 sec. Muscle tension of the right triceps surae was measured at 450 deg/sec of passive ankle dorsiflexion on the day before and 3, 7, and 14 days after PRF or sham operation. Locomotive function was evaluated by obtaining Basso, Beattie, and Bresnahan (BBB) scores. RESULTS: Muscle tension of the triceps surae decreased significantly three days after PRF, and gradually returned to baseline 14 days later. In the sham operation group, muscle tension increased significantly more than 14 days. The BBB scores declined from 10 to 8 after PRF and returned to pre-PRF levels 14 days later, while scores remained constant after sham operation. CONCLUSIONS: PRF produced significant and reversible suppression in spasticity, but this was accompanied by deterioration in locomotive function. Thus, caution should be exercised in considering the benefits and costs in suppressing spasticity in ambulatory patients, and implanted devices that apply titratable doses of PRF may be best to optimize patients' needs.

Demographic and Symptomatic Features of Voice Disorders and Their Potential Application in Classification Using Machine Learning Algorithms.

BACKGROUND: Studies have used questionnaires of dysphonic symptoms to screen voice disorders. This study investigated whether the differential presentation of demographic and symptomatic features can be applied to computerized classification. METHODS: We recruited 100 patients with glottic neoplasm, 508 with phonotraumatic lesions, and 153 with unilateral vocal palsy. Statistical analyses revealed significantly different distributions of demographic and symptomatic variables. Machine learning algorithms, including decision tree, linear discriminant analysis, K-nearest neighbors, support vector machine, and artificial neural network, were applied to classify voice disorders. RESULTS: The results showed that demographic features were more effective for detecting neoplastic and phonotraumatic lesions, whereas symptoms were useful for detecting vocal palsy. When combining demographic and symptomatic variables, the artificial neural network achieved the highest accuracy of 83 ± 1.58%, whereas the accuracy achieved by other algorithms ranged from 74 to 82.6%. Decision tree analyses revealed that sex, age, smoking status, sudden onset of dysphonia, and 10-item voice handicap index scores were significant characteristics for classification. CONCLUSION: This study demonstrated a significant difference in demographic and symptomatic features between glottic neoplasm, phonotraumatic lesions, and vocal palsy. These features may facilitate automatic classification of voice disorders through machine learning algorithms.

Effect of polymyxin resistance (pmr) on biofilm formation of Cronobacter sakazakii.

Cronobacter sakazakii (C.sakazakii) has been identified as a wide-spread conditioned pathogen associated with series of serious illnesses, such as neonatal meningitis, enterocolitis, bacteremia or sepsis. As food safety is concerned, microbial biofilm has been considered to be a potential source of food contamination. The current study aims to investigate the ability of biofilm formation of two C. sakazakii strains (wild type BAA 894 and pmrA mutant). Crystal violet (CV), XTT (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino carbonyl)-2H-(tetrazolium hydroxide)] assays, and scanning electron microscopy (SEM) are performed on different time points during biofilm formation of C. sakazakii strains. Furthermore, RNA-seq strategy is utilized and the transcriptome data is analyzed to study the expression of genes related to biofilm formation along with whole genome sequencing. For biomass, in the first 24 h, pmrA mutant produced approximately 5 times than wildtype. However, the wild type exhibited more biomass than pmrA mutant during the post maturation stage (7-14 d). In addition, the wildtype showed higher viability than pmrA mutant during the whole biofilm formation. This study represents the first evidence on the biofilm formation of C. sakazakii pmrA mutant, which may further aid in the prevention and control for the food contamination caused by C. sakazakii.

Reversion of gold nanoparticle aggregates for the detection of Cu2+ and its application in immunoassays.

A high concentration of copper is a hazardous element to organisms and human health. Although various strategies have been reported for the sensitive detection of copper, a facile and rapid detection of aqueous copper has seldom been addressed to date. Here, we present an easy and accessible colorimetric method to detect Cu2+ using the redispersion of cysteamine-modified gold nanoparticles (CA-AuNPs). Initially, CA caused the aggregation of AuNPs due to the electrostatic interaction and aggregated AuNPs can be regenerated in basic medium. The subsequent addition of Cu2+ to the CA-AuNP dispersion could effectively trigger the aggregation of CA-AuNPs, resulting from the coordination reactivity between the deprotonated CA and Cu2+. This strategy resulted in a detection limit (LOD) of 1.52 µM in drinking water, which is below the U.S. Environmental Protection Agency permissible limit (20 µM). To demonstrate the broad application of CA-AuNPs, we further applied this method to plasmonic immunoassays based on the competitive interaction of Cu2+ between CA-AuNPs and enzymes. The LOD of the Down syndrome biomarker hyperglycosylated human chorionic gonadotropin (H-hCG) was 0.125 mIU mL-1, which is better than that of commercial immunoassays. Importantly, the determination of H-hCG in serum indicates its applicability for the measurement of real samples. Our assay agrees well with the current immunoassay systems and thus it can easily be expanded to a more common sensing platform for different types of biotargets by changing the corresponding antibodies.

Effects of pulsed-radiofrequency neuromodulation on the rat with overactive bladder.

AIM: To quantify the effects of pulsed radiofrequency (PRF) electrical stimulations of the pudendal and pelvic nerves on the bladder function of rats with detrusor overactivity. METHODS: All rats were pretreated with a continuous transvesical infusion of 0.5% acetic acid (AA) for inducing detrusor overactivity. Intravesical pressure was recorded using cysometrography (CMG) during the continuous transvesical infusion to examine the effects of PRF electrical stimulation of the pudendal and pelvic nerves individually. In addition, the activity of caspase-3, an apoptosis marker, in the pelvic nerve was examined to evaluate the impact of PRF on nerve injury. RESULTS: According to the first CMG recording, AA treatment significantly reduced bladder capacity (BC) and intercontraction interval (ICI) to 65% and 66% of the corresponding control values, respectively. Subsequently, PRF electrical stimulation of the pelvic nerve inhibited AA-induced detrusor overactivity and significantly increased BC to approximately 102-110% and ICI to 79-92%; these effects persisted for at least 4 h. Furthermore, PRF did not cause significant neural damage to the target stimulated nerves, as demonstrated by caspase-3 activity. CONCLUSION: PRF electrical stimulation of pelvic nerves exerted a long-lasting effect of suppressing AA-induced detrusor overactivity. This modality can be used as an alternative approach for improving bladder continence in patients with overactive bladder syndrome.

Effects of pudendal neuromodulation on bladder function in chronic spinal cord-injured rats.

BACKGROUND/PURPOSE: Few studies have investigated the feasibility of using pudendal neuromodulation to regulate bladder function in spinal cord-injured (SCI) animals. The present study aimed to determine the effects of electrical activation of the pudendal sensory branch on improving voiding functions in rats 6 weeks after a spinal cord injury and to explore the underlying neuromodulatory mechanisms. METHODS: Two urodynamic measurements were used to assess the effects of electrical stimulation (ES) on bladder and urethral functions: simultaneous recordings of the intravesical pressure (IVP) during continuous isotonic transvesical infusion (i.e., isotonic IVP) and external urethral sphincter (EUS) electromyography (EUS-EMG), and simultaneous recordings of transvesical pressure under isovolumetric conditions (i.e., isovolumetric IVP) and urethral perfusion pressure (UPP). RESULTS: Six weeks after the SCI, the rats showed voiding dysfunction, as indicated by abnormal cystometric measurements (e.g., increased volume threshold, increased contraction amplitude, and increased residual volume, and decreased voided volume). The voiding efficiency (VE) decreased to 13% after the SCI, but increased to 22-34% after applying pudendal afferent stimulation. In addition, pudendal stimulation significantly increased the EUS burst period and increased the difference between the UPP and the high-frequency oscillation (HFO) baselines, and changed the time offset between bladder and EUS activities. These findings suggest that pudendal afferent stimulation improved the VE by prolonging the micturition interval, decreased the urethral resistance, and recovered detrusor-sphincter dyssynergia during the voiding phase. CONCLUSION: This study demonstrates the feasibility of using pudendal neuromodulation in chronic SCI rats. These results could aid in developing an advanced neural prosthesis to restore bladder function in clinical settings.

Characteristic investigation of scanning surface plasmon microscopy for nucleotide functionalized nanoarray.

A calculation based on surface plasmon coupling condition and Maxwell-Garnett equation was performed for predicting the coupling angle shift and thin film thickness in scanning surface plasmon microscopy (SSPM). The refractive index sensitivity and lateral resolution of an SSPM system was also investigated. The limit of detection of angle shift was 0.01°, the limit of quantification of angle shift was 0.03°, and the sensitivity was around 0.12° shift per nm ZnO film when the film thickness was less than 22.6 nm. Two partially connected Au nano-discs with a center-to-center distance of 1.1 µm could be identified as two peaks. The system was applied to image nanostructure defects and a virus-probe functionalized nanoarray. We expect the potential application in nanobiosensors with further optimization in the future.

Nonfouling property of zwitterionic cysteine surface.

Applications of implantable bioelectronics for analytical and curative purposes are currently limited by their poor long-term biofunctionality in physiological media and nonspecific interactions with biomolecules. In an attempt to prolong in vivo functionality, recent advances in surface modifications have demonstrated that zwitterionic coatings can rival the performance of conventional poly(ethylene glycol) polymers in reducing nonspecific protein fouling. Herein, we report the fabrication of a very thin layer of nonfouling zwitterionic cysteine surface capable of protecting implantable bioelectronics from nonspecific adsorption of plasma proteins. This work is the first of its kind to fabricate, through solution chemistry, a cysteine surface exhibiting zwitterionic state as high as 88% and to demonstrate antibiofouling under the exposure of bovine serum albumin (BSA) and human serum. The fabricated surface utilized a minimal amount of gold substrate, approximately 10 nm, and an extremely thin antifouling layer at 1.14 nm verified by ellipsometry. X-ray photoelectron spectroscopy assessment of the nitrogen (N1s) and carbon (C1s) spectra conclude that 87.8% of the fabricated cysteine surface is zwitterionic, 2.5% is positively charged, and 9.6% is noncharged. Antibiofouling performance of the cysteine surface is quantitatively determined by bicinchoninic acid (BCA) protein assay as well as qualitatively confirmed using scanning electron spectroscopy. Cysteine surfaces demonstrated a BSA fouling of 3.9 ± 4.84% µg/cm(2), which is 93.6% and 98.5% lower than stainless steel and gold surfaces, respectively. Surface plasmon resonance imaging analysis returned similar results and suggest that a thinner cysteine coating will enhance performance. Scanning electron microscopy confirmed the results of BCA assay and suggested that the cysteine surface demonstrated a 69% reduction to serum fouling. The results reported in this paper demonstrate that it is possible to achieve a highly zwitterionic surface through solution chemistry on a macroscopic level that is capable of improving biocompatibility of long-term implantable bioelectronics.

Label-free colorimetric aptasensor for IgE using DNA pseudoknot probe.

The development of simple and low-cost approaches to the detection of immunoglobulin E (IgE) would provide a method for the early diagnosis and prevention of atopic diseases. The current methods of detection are generally tedious, multi-step processes and are limited by the high cost of the labeled proteins. We describe here a label-free structure-switching colorimetric method for the simple measurement of IgE using DNA pseudoknot probes and gold nanoparticles. In the absence of a target the IgE aptamer probe adopts a pseudoknot conformation that dissociates a capture probe from the unmodified gold nanoparticles. However, when IgE binds to the aptamer probe, the pseudoknot is resolved, leading to a favorable hybridization between the 3' terminal loop of the aptamer probe and the capture probe; this induces the aggregation of the gold nanoparticles. As a result, the colorimetric IgE sensor using this structure-switching mechanism is sensitive, specific and convenient, and the assay works even when challenged with complicated biological matrixes such as vaginal fluids. The proposed method is expected to be of great clinical value for IgE detection and could be used, after appropriate design, for sensing applications of other structured aptamers.

Loop-mediated isothermal amplification assays for screening of bacterial integrons.

BACKGROUND: The occurrence and prevalence of integrons in clinical microorganisms and their role played in antimicrobial resistance have been well studied recently. As screening and detection of integrons are concerned, current diagnostic methodologies are restricted by significant drawbacks and novel methods are required for integrons detection. RESULTS: In this study, three loop-mediated isothermal amplification (LAMP) assays targeting on class 1, 2 and 3 integrons were implemented and evaluated. Optimization of these detection assays were performed, including studing on the reaction temperature, volume, time, sensitivity and specificity (both primers and targets). Application of the established LAMP assays were further verified on a total of 1082 isolates (previously identified to be 397 integron-positive and 685 integron-negative strains). According to the results, the indispensability of each primer had been confirmed and the optimal reaction temperature, volume and time were found to be 65°C, 45 min and 25 µL, respectively. As application was concerned, 361, 28 and 8 isolates carrying intI1, intI2 and intI3 yielded positive amplicons, respectively. Other 685 integron-negative bacteria were negative for the integron-screening LAMP assays, totaling the detection rate and specificity to be 100%. CONCLUSIONS: The intI1-, intI2- and intI3-LAMP assays established in this study were demonstrated to be the valid and rapid detection methodologies for the screening of bacterial integrons.

Closed-Loop Deep Brain Stimulation With Reinforcement Learning and Neural Simulation.

Deep Brain Stimulation (DBS) is effective for movement disorders, particularly Parkinson's disease (PD). However, a closed-loop DBS system using reinforcement learning (RL) for automatic parameter tuning, offering enhanced energy efficiency and the effect of thalamus restoration, is yet to be developed for clinical and commercial applications. In this research, we instantiate a basal ganglia-thalamic (BGT) model and design it as an interactive environment suitable for RL models. Four finely tuned RL agents based on different frameworks, namely Soft Actor-Critic (SAC), Twin Delayed Deep Deterministic Policy Gradient (TD3), Proximal Policy Optimization (PPO), and Advantage Actor-Critic (A2C), are established for further comparison. Within the implemented RL architectures, the optimized TD3 demonstrates a significant 67% reduction in average power dissipation when compared to the open-loop system while preserving the normal response of the simulated BGT circuitry. As a result, our method mitigates thalamic error responses under pathological conditions and prevents overstimulation. In summary, this study introduces a novel approach to implementing an adaptive parameter-tuning closed-loop DBS system. Leveraging the advantages of TD3, our proposed approach holds significant promise for advancing the integration of RL applications into DBS systems, ultimately optimizing therapeutic effects in future clinical trials.

Organic-based plasmonic emitters for sensing applications.

Plasmonic emissions generated by excitation of an organic layer on a metal grating structure are demonstrated. The emissions correspond to the resonant condition of surface plasmon (SP) modes on the Alq(3)/Au interface, and the grating structure is coupled to the Au/air interface to provide light emissions. Experimental variations in pitch to control plasmonic bandgap obtained highly directional plasmonic emissions with enhanced intensity. This method is readily applicable for detecting refractive index changes by using SP-coupled fluorophores to obtain emissions of varying wavelengths and viewing angles. The calculations showed that the wavelength of the plasmonic emitter changed from 480 to 680 nm at certain viewing angles, while the concentration of contacting glucose increased from 10% to 40%. Accordingly, a device with a pitch size of 500 nm had a sensitivity of Δθe/Δn=37.76° and Δn/Δ=1.681×10(-4) RIU (refractive index unit). Therefore, the proposed approach has potential applications in low-cost, disposable, point-of-care biosensors.

Soft stethoscope for detecting asthma wheeze in young children.

Asthma is a chronic disease that is commonly suffered by children. Asthmatic children have a lower quality of life than other children. Physicians and pediatricians recommend that parents record the frequency of attacks and their symptoms to help manage their children's asthma. However, the lack of a convenient device for monitoring the asthmatic condition leads to the difficulties in managing it, especially when it is suffered by young children. This work develops a wheeze detection system for use at home. A small and soft stethoscope was used to collect the respiratory sound. The wheeze detection algorithm was the Adaptive Respiratory Spectrum Correlation Coefficient (RSACC) algorithm, which has the advantages of high sensitivity/specificity and a low computational requirement. Fifty-nine sound files from eight young children (one to seven years old) were collected in the emergency room and analyzed. The results revealed that the system provided 88% sensitivity and 94% specificity in wheeze detection. In conclusion, this small soft stethoscope can be easily used on young children. A noisy environment does not affect the effectiveness of the system in detecting wheeze. Hence, the system can be used at home by parents who wish to evaluate and manage the asthmatic condition of their children.

Ultrasound-Guided Perineural Vitamin B12 Injection for Brachial Plexus Injury: A Preliminary Study.

Individuals with brachial plexus injury (BPI) require upper limb function restoration, but the treatment remains controversial. Vitamin B12 may aid in pain control and nerve regeneration. We present the technical aspects of ultrasound-guided perineural vitamin B12 injection for BPI. The demonstrative case is a 50-year-old man with BPI resulting from a traffic accident. Under ultrasound guidance, vitamin B12 was injected precisely into the brachial plexus compartment around the swollen neuroma of the C6 root. Motor and sensory functions of the left upper extremity improved over 6 months. Ultrasound-guided perineural vitamin B12 injection may be an efficient and personalized intervention in cases of post-ganglionic BPI that failed to improve in the first 3 months.

The clinicopathological and genetic differences among gastric cancer patients with no recurrence, early recurrence, and late recurrence after curative surgery.

BACKGROUND: To date, few reports have investigated the genetic alterations and clinicopathological features among gastric cancer (GC) patients with no tumor recurrence, early recurrence, and late recurrence following curative surgery. METHODS: A total of 473 GC patients undergoing curative surgery were included. The clinicopathological characteristics, patient prognosis, recurrence patterns, and genetic alterations were compared between GC patients with early recurrence and late recurrence. RESULTS: Among the 473 GC patients, 119 had early recurrence (<2 years) and 45 had late recurrence (≥2 years). Patients with early recurrence had tumor size larger than 5 cm, fewer superficial-type tumors, more lymphovascular invasion, more advanced pathological T and N categories and Tumor, Node, Metastasis (TNM) stages, and worse 5-year overall survival than patients with late recurrence and no recurrence. For intestinal-type GC, patients with no tumor recurrence had more Helicobacter pylori infection than patients with early recurrence and late recurrence; for diffuse-type GC patients, the frequency of PIK3CA amplification was the highest in early recurrence, followed by late recurrence and no recurrence. GC patients with single-site recurrence had more ARID1A mutations than those with multiple-site recurrence. Multivariate analysis demonstrated that age, tumor recurrence, and pathological N categories were independent prognostic factors. CONCLUSION: PIK3CA amplifications were more common in diffuse-type GC with early recurrence, whereas ARID1A mutations were more common in patients with single-site recurrence. Targeted therapy and immunotherapy might be helpful for these patients.

Dependence of transport rate on area of lithography and pretreatment of tip in dip-pen nanolithography.

This study examines the lithographic capacity of tips in dip-pen nanolithography (DPN). The dependence of the transport rate (R) decay on the area of lithography (A(lith)), the dependence of A(lith) on the lithographic time (t), and the effect of piranha cleaning on the lithographic capacity are considered herein. The dependencies in the line-drawing lithography process are studied using 16-mercaptohexadecanoic acid (MHA) ink. On the basis of the linear decay dependence discovered in the R-A(lith) dependence, piranha treatment can increase the lithographic capacity by up to 35.5-fold, an improvement that may originate from a change in the tip's surface chemistry. Moreover, a theoretical model is derived to describe the A(lith)-t dependence accurately and to predict the tips' lifetime. Furthermore, an experiment involving DPN-based nanostructure fabrication demonstrates the importance of monitoring the tips' transport rate and lifetime. In addition to shedding light on the physical and chemical principles behind DPN, this study provides a comprehensive model for a quantitative analysis of the tips' behavior.