Quantitative and Qualitative Examination of Particle-particle Interactions Using Colloidal Probe Nanoscopy
Summary
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.
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 interactions between the probe and the sample, the cantilever is deflected during contact or proximity and depending on the mode of operation, this deflection can be translated to acquire the topography of the sample or measure forces present between the probe and sample. Modifications to the AFM technique, such as colloidal probe nanoscopy,10 have allowed scientist to directly evaluate the nano-force interactions between two materials present in a colloidal system of interest.
In colloidal probe nanoscopy, a spherical particle of choice is attached to the apex of a cantilever, replacing the traditional conical and pyramidal tips. A spherical particle is ideal to allow comparison with theoretical models such as the Johnson, Kendal, Roberts (JKR)11 and Derjaguin, Landau, Vervwey, Overbeek (DLVO)12-14 theories and to minimize the influence of surface roughness on the measurement.15 These theories are used to define the contact mechanics and inter-particle forces expected within a colloidal system. The DLVO theory combines the attractive van der Waal forces and repulsive electrostatic forces (due to electrical double layers) to quantitatively explain the aggregation behavior of aqueous colloidal systems, while the JKR theory incorporates the effect of contact pressure and adhesion to model elastic contact between two components. Once an appropriate probe is produced, it is used to approach any other material/particle to evaluate the forces between the two components. Using a standard manufactured tip one will be able to measure interactive forces between that tip and a material of choice, but the benefit of using a custom made colloidal probe allows the measurement of forces present between materials present within the studied system. Measurable interactions include: adhesive, attractive, repulsive, charge, and even electrostatic forces present between the particles.16 Additionally, the colloidal probe technique can be used to explore tangential forces present between particles and material elasticity.17,18
The ability to conduct measurements in various media is one of the major advantages of colloidal probe nanoscopy. Ambient conditions, liquid media, or humidity-controlled conditions can all be used to mimic environmental conditions of the system studied. The ability to conduct measurements in a liquid environment enables the study of colloidal systems in an environment that it naturally occurs; thus, being able to quantitatively acquire data that is directly translatable to the system in its natural state. For example, particle interactions present within metered dose inhalers (MDI) can be studied using a model liquid propellant with similar properties to the propellant used in MDIs. The same interactions measured in air would not be representative of the system existent in the inhaler. Furthermore, the liquid medium can be modified to evaluate the effect of moisture ingress, a secondary surfactant, or temperature on the particle interactions in an MDI. The ability to control temperature can be used to mimic certain steps in the manufacturing of colloidal systems to evaluate how temperature either in the manufacturing of or storage of colloidal systems may have an impact on particle interactions.
Measurements that can be obtained using colloidal probes include; Topography scanning, individual force-distance curves, force-distance adhesion maps, and dwell force-distance measurements. Key parameters that are measured using the colloidal probe nanoscopy method presented in this paper include the snap-in, max load, and separation energy values. Snap-in is a measurement of the attractive forces, max load the value of the maximum adhesion force, and the separation energy conveys the energy required to withdraw the particle from contact. These values can be measured through instantaneous or dwell force measurements. Two different types of dwell measurements include deflection and indentation. The length and type of dwell measurement can be specifically chosen to mimic specific interactions that are present within a system of interest. An example is using deflection dwell – which holds the samples in contact at a desired deflection value – to evaluate the adhesive bonds that develop in aggregates formed in dispersions. The adhesive bonds formed can be measured as a function of time and can provide insight into the forces required to redisperse the aggregates after prolonged storage. The plethora of data that can be obtained using this method is a testament to the versatility of the method.
Protocol
Representative Results
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 …
Divulgaciones
The authors have nothing to disclose.
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 Project grant (LP120200489, LP110200316).
Materials
| Name of Material/ Equipment | Company | Catalog Number | Comments/Description |
| Double-Bubble Epoxy | Hardman | 4004 | |
| Veeco Tipless Probes | Veeco | NP-O10 | |
| Porous Particles | Pearl Therapeutics | N/A | |
| Atomic Force Microscope (MFP) | Asylum | MFP-3D | |
| SPIP Scanning Probe Image Processor Software | NanoScience Instruments | N/A | |
| 35 mm Coverslips | Asylum | 504.003 | |
| Tempfix | Ted Pella. Inc. | 16030 |
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