Colloidal probe nanoscopy can be used within a variety of fields to gain insight into the physical stability and coagulation kinetics of colloidal systems and aid in drug discovery and formulation sciences using biological systems. The method described within provides a quantitative and qualitative means to study such systems.
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Method Article
Quantitative and Qualitative Examination of Particle-particle Interactions Using Colloidal Probe Nanoscopy
In This Article
Summary
Abstract
Colloidal Probe Nanoscopy (CPN), the study of the nano-scale interactive forces between a specifically prepared colloidal probe and any chosen substrate using the Atomic Force Microscope (AFM), can provide key insights into physical interactions present within colloidal systems. Colloidal systems are widely existent in several applications including, pharmaceuticals, foods, paints, paper, soil and minerals, detergents, printing and much more.1-3 Furthermore, colloids can exist in many states such as emulsions, foams and suspensions. Using colloidal probe nanoscopy one can obtain key information on the adhesive properties, binding energies and even gain insight into the physical stability and coagulation kinetics of the colloids present within. Additionally, colloidal probe nanoscopy can be used with biological cells to aid in drug discovery and formulation development. In this paper we describe a method for conducting colloidal probe nanoscopy, discuss key factors that are important to consider during the measurement, and show that both quantitative and qualitative data that can be obtained from such measurements.
Introduction
Atomic force microscopy (AFM) is a technique that enables qualitative and quantitative imaging and probing of a material surface.4-6 Traditionally, AFM is used for the evaluation of surface topography, morphology and structure of multi-phasic materials. AFM has the capability to quantitatively evaluate nano-scale interactions, such as charge, attraction, repulsion and adhesion forces between a specific probe and substrate in both air and liquid mediums.7,8 The AFM originally developed by Binning, Quate and Gerber9 uses a probe of known/determined sensitivity and spring constant to approach and/or scan a sample. Due to the physical inte....
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Protocol
1. Preparing the Colloidal Probe and AFM Substrate
- To prepare colloidal probes, use a method developed previously by the authors.19
- In brief, use a 45° angle holder to affix a tipless cantilever at the specific angle of 45° (Figure 1A).
- Prepare an epoxy slide by smearing a thin layer of epoxy onto a microscope slide. Use a clean spatula or a slow stream of nitrogen to ensure that the layer of epoxy added to the microscope slide is of minimal height.
- Affix the epoxy slide to a 40X optical zoom microscope lens using a custom designed holder (Figure 1B). Then use the cant....
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Results
Liquid colloidal systems are used for several pharmaceutical drug delivery systems. For inhalation drug delivery, a common colloidal system is the suspension pressurized metered dose inhaler (pMDI). Particle interactions present within the pMDI play a vital role in formulation physical stability, storage, and drug delivery uniformity. In this manuscript, inter-particle forces between porous lipid-based particles (~2 µm optical mean particle diameter) in a model propellant (2H,3H-perfluoropentane) were evaluated at RT to .......
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Discussion
Several sources of system instability present during liquid colloidal probe nanoscopy can easily be mitigated through proper equilibration procedures. Instabilities as discussed previously result in erroneous results and force curves that are more difficult to analyze objectively. If all sources of instability have been tended and graphs similar to that shown in Figure 4 are still present, another measurement parameter may be the reason. Other measurement parameters that are important to consider during .......
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Disclosures
The authors declare that they have no competing financial interests.
Acknowledgements
The authors acknowledge (1) financial supports from Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine in Dankook University, and from the Priority Research Centers Program (No. 2009-0093829) funded by NRF, Republic of Korea, (2) the facilities, and the scientific and technical assistance, of the Australian Centre for Microscopy and Microanalysis at the University of Sydney. HKC is grateful to the Australian Research Council for the financial supports through a Discovery Project grant (DP0985367& DP120102778). WCh is grateful to the Australian Research Council for the financial supports through a linkage Proje....
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Materials
| Name | Company | Catalog Number | Comments |
|---|---|---|---|
| Double-Bubble Epoxy | Hardman | 4004 | |
| Veeco Tipless Probes | Veeco | NP-O10 | |
| Porous Particles | Pearl Therapeutics | ||
| Atomic Force Microscope (MFP) | Asylum | MFP-3D | |
| SPIP Scanning Probe Image Processor Software | NanoScience Instruments | ||
| 35 mm Coverslips | Asylum | 504.003 | |
| Tempfix | Ted Pella. Inc. | 16030 |
References
- Sindel, U., Zimmermann, I. Measurement of interaction forces between individual powder particles using an atomic force microscope. Powder Technology. 117, 247-254 (2001).
- Ducker, W. A., Senden, T. J., Pashley, R. M. Direct measurement of colloid....
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