Since neither your undiluted nor diluted samples are giving you results, maybe we can look at the dilution.

Here are a few things you could try, just suggestions:

• Dilution Medium: Type I water is definitely not going to work because zeta potential measurements need some level of ionic strength. And 0.0035 mM saline might be too dilute – if the ion concentration is too low, the conductivity will be insufficient, leading to a weak signal. I'd recommend diluting with a slightly higher concentration electrolyte solution. For example, you could try 1-10 mM phosphate buffer (pH 7.4), or 1-10 mM NaCl solution.
• Dilution Ratio: The dilution ratio is also key – too concentrated or too dilute, and you'll run into problems. A good starting point would be to dilute at a 1:10 or 1:20 ratio. Then, use the automatic attenuator function in the Zetasizer software to check if the scattering intensity is in the right range. If it's too high, dilute further; if it's too low, reduce the dilution. The goal is to get the scattering intensity within the optimal measurement range for the Zetasizer.

Some Quick Measurement Tips:

• Clean sample: Filtering (0.22 μm) to get rid of aggregates might make a difference.
• Bubbles out: Letting the sample settle or a quick spin in a centrifuge could help with bubbles.
• Settings: The default Zetasizer settings are usually a good starting point.
• Run it a few times: Measuring 3+ times and averaging might give you more consistent data.
• Use reliable buffers and salts: Regents from companies like MedChemExpress, BOC Sciences, Thermo Fisher Scientific are worth checking out.

Hopefully, trying some of these suggestions will help you nail those zeta potential readings!

Hello Karen!

To measure the zeta potential of your liposome sample using Malvern's Zetasizer, prepare the sample by diluting it in a low-conductivity buffer (e.g., 10 mM NaCl or PBS) to optimize scattering intensity. Optionally, sonicate briefly and filter through a 0.22 µm or 0.45 µm membrane to remove aggregates. Load ~1 mL of the diluted sample into a folded capillary cell (DTS1070), ensuring no air bubbles.

The electrodes inside the capillary cell generate an electric field, causing charged liposomes to migrate based on their electrophoretic mobility. Insert the folded capillary cell with electrodes properly positioned into the Zetasizer. Configure instrument parameters (temperature, dielectric constant, viscosity) and initiate measurement. The instrument applies an electric field, detects particle movement using laser Doppler electrophoresis, and calculates zeta potential using the Smoluchowski or Henry equation. Ensure stable phase plots and minimal noise for accurate readings.

Pls feel free for any further discussion.