Research and Instruments

Characterisation of pharmaceutical systems and their behaviour on the micro-and nano-scales is essential to ensure the quality, efficacy and safety of medicines. We use innovative label-free spectroscopic and imaging approaches as well as complementary methods to expose secrets behind optimal pharmaceutical performance.
Pharmaceutical formulations

We aim to better understand the nano and microstructures of drug particles and dosage forms by employing the latest vibrational spectroscopic and imaging methods in new ways. In particular we use spontaneous and coherent Raman techniques with complementary non-linear optical imaging modalities. We are especially interested in detecting and understanding the behaviour of trace and surface structures, including variations in crystallinity and component distribution, which can have a highly detrimental effect of pharmaceutical quality and safety, and at the same time, are difficult to detect with established analytical approaches.

Biomedical Applications

One part of our research group’s research interests is biological/biomedical applications of vibrational spectroscopic methods and non-linear optical imaging. In this field, we have studied especially nanoparticle-cell interactions and cellular drug uptake. One of our current research projects focuses on label-free characterisation of drug-loaded polymeric nanoparticles and the study of their interactions with cells. We combine Raman spectroscopic methods with non-linear optical imaging including sum-frequency generation (SFG) and two-photon fluorescence (TPF) microscopy.

Another research project focuses on label-free characterisation of drug resistant and non-resistant cancer cells, with the aim of better understanding the development of treatment resistance in cancer. We also have experience and interests in the analysis of biological tissue with multimodal non-linear optical imaging as well as the characterisation of extracellular vesicles by Raman spectroscopy. With image and data-analysis, we utilise novel and established multivariate data-analysis methods.

Instruments

These are some of the instruments that we are responsible for or are important for our research.

Timegated Raman spectrometers: Timegate M1 + microscope (Olympus BX53) and Timegate Picoraman with BWTek probe

With time-gating technology, it is possible to avoid fluorescence by controlling the period during which the detector is collecting light after the laser pulse. Since Raman scattering occurs before fluorescence after the laser pulse, it is possible to separate Raman scattering from fluorescence. This technology also enables measurements of thermally emitting hot samples and measurements in illuminated environment.

Instruments are equipped with 532 nm pulsed lasers and can be used for recording single spectrum, either with a probe or with a microscope. These techniques are especially suitable for measuring fluorescent samples, which could not be measured with conventional Raman spectroscopy.

The Timegated Raman instruments are located at the Faculty of Pharmacy, first floor.

Confocal Raman Microscope + AFM (NT-MDT NTEGRA Spectra)

The instrument can be used both for recording single spectrum as well as for mapping. The excitation lasers are 532 nm (green) and 633 nm (red).

Applications of confocal Raman microscopy in pharmaceutical research include e.g. studying intracellular drug delivery, probing the distribution of components within a pharmaceutical formulation and characterization of the solid state of active pharmaceutical ingredients.

The instrument is located in Markku Vainio's laser spectroscopy laboratory at the Department of Chemistry.

FT-IR infrared spectrometer (Thermo Scientific Nicolet iS50)
  • Measurements in mid- IR and far-IR regions.
  • Sampling in transmission or reflection (ATR) modes.
  • Includes an ATR module Harrick ConcentratIR2 with a diamond crystal.
  • Sampling possibilities for solids, liquids, pastes and slurries.
  • Also possibility for temperature controlled measurements with temperature controller.
X-Ray Powder Diffraction (Malvern PANanalytical Empyrean)

This instrument allows users to detect trace crystallinity, determine crystal structures and detect polymorphs in powders. Sample holders and Kapton/Mylar film are provided for sample preparation. The software allows users to create custom programs which can then be executed automatically. It can be used in transmission or in reflection mode.

Infrared Laser Ablation Mass Spectrometry Imaging platform

The in-house developed Infrared Laser Ablation Mass Spectrometry Imaging (IRLA-MSI) platform offers untargeted and label-free imaging for simultaneous measurement of hundreds of analytes. IRLA-MSI reveals how different analytes are distributed in solid and planar ex vivo samples, such as tissue sections or plant leaves.

The method is best suited for the analysis of small <1500 Da molecules, and it can cover the analysis of small nonpolar, neutral polar, and charged polar molecules, such as various metabolites, neurotransmitters, lipids, and pharmaceutical compounds. IRLA-MSI measurements are carried out with minimal sample preparation and without treatment, which allows straightforward analysis of frozen biological samples in their native metabolic state.

The instrument is located in the Laboratory of Mass Spectrometry at the Faculty of Pharmacy, first floor.

Differential scanning calorimeter (Mettler Toledo DSC823e)

This instrument is a quick and easy way for characterizing the solid state of compounds. Sample insertion is fully automated and sample holders are provided. Liquid nitrogen cooling allows a temperature range between -150°C and 500°C. Calibration is performed regularly using iridium standards. The instrument also supports modulated temperature DSC (separate non-reversing/reversing/total heat flow analysis is possible).

The included STARe software allows users to create custom programs and analyse their data (peak integration, glass transition temperature determination, and so forth).

Polarized Light Microscope (Leica DLMB-T) with a hot stage (Mettler Toledo FP82HT)

The polarized light microscope allows users to directly see crystallinity or study other birefringent phenomena in their samples. The user has a choice between x2.5, x5, x10, x20 and x50 magnification (eyepiece lens: x10, field number: 20mm) using either polarized or non-polarized light.

The microscope is connected to a Leica camera that allows the user to take pictures. The hot stage allows users to perform experiments at increased temperatures.

Hot Melt Extruder (Three Tec- ZE9)

Multifunction extrusion of “small and smallest” quantities of various materials in laboratory, test and small production applications. This Extruder is used for complex extrusion tasks under difficult conditions such as very high pressure, high torque and step temperature profile. The parallel Twin-Screw Extruders are fitted with easily replaceable barrels and screws that can be configured to your needs. Various screw segments can be combined to convey, knead and mix the extrudate. 

It consists of three heating-zones whose temperature can be controlled separately and is recorded with the torque of the motor by the control system. Records can be transferred to USB or via Ethernet.

The extruder is located at the Faculty of Pharmacy, third floor.