Tunable Resistive Pulse Sensing (TRPS)-Based Exosome Characterization Service

Q: Q1: What are the limitations of TRPS for exosome analysis?

A: Potential pore clogging and background noise in complex samples are known challenges. At Creative Biostructure, we apply optimized buffers and pre-filtration steps to minimize these effects.

Q: Q2: How does TRPS compare to other exosome characterization methods?

A: TRPS provides single-particle resolution and multiparametric data (size, concentration, charge). Unlike NTA or DLS, it yields absolute counts and higher accuracy for heterogeneous populations.

Q: Q3: What are the applications of TRPS in exosome research?

A: TRPS is widely used for biomarker discovery, therapeutic exosome development, and quality control of engineered vesicles.

Q: Q4: How much sample is required for TRPS analysis?

A: Typically ≥100 μL with a concentration of 10 9 -10 10 particles/mL. For precious samples, please contact us for low-volume options.

Q: Q5: How long does TRPS analysis take once I submit my samples?

A: Typical turnaround time is 1-2 weeks depending on sample complexity and project scope. Expedited service is available for time-sensitive studies.

Exosomes are nanoscale extracellular vesicles (EVs) typically ranging from 30-150 nm in diameter. They carry bioactive molecules including proteins, lipids, and nucleic acids, acting as mediators of intercellular communication in cancer progression, immune regulation, and neurological disorders. With the growing clinical and industrial interest in exosome-based diagnostics and therapeutics, accurate and reproducible biophysical characterization has become essential.

Creative Biostructure offers a tunable resistive pulse sensing (TRPS) exosome characterization service that enables single-particle resolution and multiparametric analysis, delivering high-confidence data for both research and translational applications.

What is Tunable Resistive Pulse Sensing (TRPS)?

TRPS is an advanced implementation of Resistive Pulse Sensing (RPS), a technique based on the Coulter principle. In this method, particles suspended in an electrolyte pass through a nanopore under an applied electric field. Each particle transiently disrupts the ionic current, generating a "pulse" that is directly proportional to its size and influenced by its surface charge.

Unlike traditional RPS with fixed pores, TRPS employs stretchable, size-tunable nanopores, enabling precise adjustment of pore dimensions and voltage to analyze heterogeneous vesicle populations with higher accuracy. This flexibility makes TRPS especially suitable for exosome characterization, where size, concentration, and zeta potential are critical parameters.

Figure 1. Schematic representation of resistive pulse sensing (RPS). (a) Measurement principle showing current changes as particles pass through a nanopore, generating resistive pulses. (b) Representative signal profiles reflecting pore morphology and particle translocation characteristics, enabling particle size and concentration analysis. (Kwon Y, et al., 2022)

Why Use TRPS for Exosome Analysis?

Conventional optical techniques such as Dynamic Light Scattering (DLS) and Nanoparticle Tracking Analysis (NTA) have well-documented limitations:

DLS: Provides ensemble-averaged signals, often obscuring heterogeneity and unable to distinguish exosomes from protein aggregates.
NTA: Offers particle tracking but may suffer from high variability (>30% error in concentration estimation) and lacks charge detection.

By contrast, TRPS offers true single-particle analysis, providing:

Higher resolution of polydisperse samples.
Absolute concentration measurement without reliance on standard curves.
Capability to measure surface charge (zeta potential), which reflects membrane stability and intercellular interaction potential.

Comparison of DLS, NTA, and TRPS for Exosome Characterization

Feature	DLS	NTA	TRPS
Principle	Measures light scattering from particle motion	Tracks scattered light of single particles	Detects current pulses as particles pass a nanopore
Resolution	Low (average, poor for mixed samples)	Medium (single particles, limited accuracy)	High (single-particle, precise size & charge)
Size Range	~1 nm-6 μm	~30-1000 nm	~30-2000 nm
Concentration	Indirect, not reliable	Semi-quantitative, 20-50% error	Absolute count, <5% error
Zeta Potential	Bulk measurement only	Not available	Direct, single-particle
Sample Needs	High concentration, sensitive to aggregates	Moderate volume, works with fluids	Needs optimized buffer, risk of pore clogging
Strengths	Fast, simple, good for uniform samples	Size distribution & visualization	Most accurate for size, count, and charge
Limitations	Poor for heterogeneous samples	Lower reproducibility, errors in count	More complex, needs calibration & prep
Best Use	Quick screening	General exosome sizing	Detailed, quantitative exosome analysis

Our TRPS Characterization Capabilities

Creative Biostructure provides comprehensive analysis of exosome samples using optimized TRPS workflows. Key measurable parameters include:

Size Distribution: Nanoparticle diameters measured on a particle-by-particle basis, capturing heterogeneity across subpopulations.
Concentration: Accurate quantification of vesicle numbers per unit volume.
Surface Charge (Zeta Potential): Determination of electrophoretic mobility, reflecting vesicle stability, aggregation tendencies, and potential targeting properties.

We support a wide range of sample types, including:

Cell culture supernatants
Human and animal biofluids (serum, plasma, cerebrospinal fluid, urine)
Purified exosome preparations from isolation workflows (ultracentrifugation, SEC, TFF, etc.)

Our system covers a dynamic size range from ~30 nm up to 2000 nm, enabling simultaneous detection of exosomes, microvesicles, and apoptotic bodies.

Our TRPS Exosome Characterization Workflow

At Creative Biostructure, we provide a comprehensive and standardized workflow for TRPS-based exosome characterization, ensuring every project is conducted with scientific rigor and compliance with MISEV2023 recommendations. From the initial consultation to the delivery of publication-ready reports, our process is designed to maximize data quality, reproducibility, and client confidence.

1

Project Consultation & Study Design

Project managers collaborate with clients to assess sample origin and research goals, then design tailored experimental plans with preparation guidance and defined deliverables.

2

Sample Receipt & Pre-Analytical Preparation

Clients may submit purified exosomes or request our exosome isolation service; we then verify sample quality, remove large particles, optimize dilution buffers, and document all pre-analytical steps for transparency.

3

TRPS Calibration & Instrument Setup

Calibration is performed with traceable standard beads, followed by adjustment of pore size, stretch, voltage, and pressure to match the target vesicle range, with all instrument details and calibration data documented in line with MISEV2023 guidelines.

4

Exosome Characterization

We provide real-time single-particle size profiling, absolute concentration counts without external standards, and zeta potential analysis to assess vesicle stability and interaction potential.

5

Quality Controls

Buffer-only runs define background signals, detergent-lysed controls confirm EV-specific events, and replicate measurements ensure reproducibility and robustness.

6

Data Analysis & Reporting

We deliver size, concentration, and zeta potential profiles with optional cross-validation, provide a detailed, publication-ready report, and offer expert consultation, downstream recommendations, and long-term project support.

Workflow for exosome size, concentration, and charge analysis using tunable resistive pulse sensing (TRPS). Figure 2. Project Workflow for Exosome Characterization by TRPS. (Creative Biostructure)

Sample Requirements for TRPS Measurement

To ensure accurate and reproducible TRPS analysis, Creative Biostructure recommends the following sample requirements. For rare or precious samples, customized solutions are available upon request.

Requirement	Recommended Standard	Notes
Sample Volume	≥100-200 μL	Minimum volume depends on concentration; low-volume protocols available for rare samples (≥50 μL).
Particle Concentration	≥1 × 10⁹ particles/mL (optimal: 10⁹-10¹⁰)	Lower concentrations may require enrichment or extended measurement time.
Sample Type	Purified exosomes or raw biofluids	Clients may submit pre-purified exosomes; isolation services available if needed.
Purity	Free of large debris, aggregates, or apoptotic bodies	Pre-clarification (filtration/centrifugation) recommended to prevent pore clogging.
Buffer Conditions	PBS or other low-conductivity buffers	Surfactant additives may be used to minimize aggregation and stabilize pore performance.
Replicates	≥3 runs per sample	Ensures reproducibility and statistical robustness of results.

What Deliverables Will You Receive

Size distribution histograms with single-particle resolution
Absolute concentration statistics (particles/mL)
Zeta potential profiles indicating vesicle stability
Full technical report with workflow, QC details, and instrument settings

Applications of TRPS in Exosome Research

Exosome-based drug development: Monitor particle size uniformity and surface charge of engineered or drug-loaded vesicles to ensure product consistency.
Biomarker discovery: Identify pathological changes in exosome subpopulations associated with cancer, neurodegeneration, or immune dysfunction.
Fundamental EV biology: Explore correlations between size/charge heterogeneity and biological function.
Quality control for exosome manufacturing: Verify batch reproducibility in preclinical and GMP workflows.

Why Choose Creative Biostructure?

Trusted Expertise: 10+ years in exosome and structural biology analysis.
High Accuracy: Optimized TRPS workflows with cross-validation by TEM, NTA, and more.
Comprehensive Solutions: From isolation to multiparametric characterization and reporting.
Client-Centered Support: Dedicated consultation and tailored recommendations for every project.

Case Study

Case: TRPS-Based Characterization of USC-Derived Exosomes in a Rett Syndrome Model

Background

Rett syndrome (RTT) is a neurodevelopmental disorder linked to MECP2 mutations. Human urine-derived stem cell exosomes (USC-Exos), enriched in miR-21-5p, were studied for their neurogenic potential via the EphA4/TEK pathway. Precise vesicle characterization was critical.

Methods

Exosomes were analyzed by TEM, western blot, and TRPS using the qNano platform with NP100 nanopores and CPC100 calibration beads.

Results

TRPS showed USC-Exos were mainly 50-100 nm with a concentration of 5.1 × 10¹⁰ particles/mL, consistent with TEM findings. Marker profiling confirmed purity. Functionally, miR-21-5p-rich exosomes enhanced neuronal differentiation and improved motor and cognitive function in RTT mice.

TRPS analysis of USC-Exo showing particle size distribution and concentration. Figure 3. TRPS Measurement of USC-Exo Size and Concentration. (Pan W, et al., 2021)

Conclusion

TRPS provided high-resolution size and concentration data essential for validating exosome identity and purity, ensuring reliable biological interpretation.

At Creative Biostructure, we are committed to delivering accurate, reproducible, and publication-ready exosome data through our advanced TRPS platform. Whether your project focuses on biomarker discovery, therapeutic exosome development, or quality control, our expert team is ready to support you with tailored solutions. Contact us to discuss your project and request a customized quote.

References

Pan W, Xu X, Zhang M, et al. Human urine-derived stem cell-derived exosomal miR-21-5p promotes neurogenesis to attenuate Rett syndrome via the EPha4/TEK axis. Laboratory Investigation. 2021, 101(7): 824-836.
Kwon Y, Park J. Methods to analyze extracellular vesicles at single particle level. Micro and Nano Systems Letters. 2022, 10(1): 14.
Welsh J A, Goberdhan D C I, O'Driscoll L, et al. Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches. Journal of Extracellular Vesicles. 2024, 13(2): e12404.

Frequently Asked Questions

For any inquiries, our support team is ready to help you get technical support for your research and maximize your experience with Creative Biostructure.

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