Challenges in the field of biotechnology are always evolving. So, too, must our tools and techniques for solving novel problems. Although Raman analysis has been around since 1928, the scientific community is only now beginning to embrace this technology’s improved capabilities, portability, and low cost. Raman analyses provide insight across the entire product lifecycle, from R&D to point-of-care (POC) diagnostics, and are broadly applicable to some of the industry’s most critical areas such as cancer research. With a bit of creativity and collaboration, Raman’s potential is expansive. So let’s explore what it is that makes Raman such a powerful tool and try to uncover solutions for some of biotechnology’s pressing challenges.
What is Raman?
If you are not familiar with how Raman works, here is a simplified overview.
We create a Raman signal by directing a monochromatic light source at a sample. This light interacts with the chemical bonds in the sample and is scattered to different wavelengths. We then analyze the wavelength shifts (degree of scatter) to make determinations about molecular composition. Raman information can be presented as spectral data (more traditional) or as a chemical image. Chemical images are essentially graphical representations of a collection of spectra. Each pixel in the image is its own Raman spectrum and is spatially oriented to reflect the molecular properties of the sample at a given wavelength. These unique spectra act as “signatures” for each type of material. These spectral signatures can be extremely beneficial when trying to determine whether a sample is meeting specification or contains a defect or contaminant.
Why is Raman a good fit for biotechnology?
Some of the reasons why Raman provides advantages over other spectroscopy or microscopy methods used in biotechnology are that it:
- Accommodates various sample forms (solid, liquid, powder, gas, etc.)
- Requires very little, if any, sample preparation
- Can analyze samples through packaging or container materials
- Can accommodate aqueous samples (critical for biotechnology industry)
- Has a small sample size requirement (<1um)
- Has a high spectral resolution and molecular functional group specificity
- Can analyze organic and inorganic features
- Is non destructive
- Can provide spectra in seconds
The simplicity and speed of Raman make it ideal for situations where critical work depends on timely and accurate results in order to continue processes across the product lifecycle.
How can Raman be applied across the product lifecycle?
In biotechnology applications, Raman can be applied at every phase in the product lifecycle. In the development phase Raman can be used for cellular evaluation in order to distinguish between cell lines or cell components, or, it can test the quality of raw materials. In subsequent phases, Raman can confirm the identity of intermediates or finished products and can provide feedback for cell viability and reaction monitoring (to increase yield, for example). We can also determine purity of the sample, from raw material to finished product.
What are the human impacts?
In addition to aiding in the manufacturing process, Raman has implications for affecting human lives. Moving beyond the cellular component, Raman can be used to study materials within a living entity to further understand drug efficacy and toxicology. For example, a tumor area can be imaged after injection with targeted and non-targeted nanotubes. Using Raman, the analyst can deduce that the targeted nanotubes are localizing in the tumor, but the non-targeted nanotubes are not. This insight helps achieve better drug delivery or diagnostic information because one can see exactly where treatment needs to be focused.
Raman also shows potential in point-of-care applications through both direct analysis and immunoassay. Direct analysis applications are already commercially available for some types of disease. For example, some instruments are specially adapted to detect skin cancer, while others are configured to rapidly detect bacteria, which is useful in cases of infection diagnosis. One application, still in development, uses nail clippings to identify osteoporosis.
Immunoassay techniques using dipstick methods and well plate analyses can also help diagnose diseases. Many of these techniques utilize surface-enhanced Raman spectroscopy (SERS). When SERS is applied, Raman interprets the result of the test similar to how your eyes interpret a positive or negative result of a color-based pregnancy test. This automatic interpretation helps to lessen the opportunity for human errors.
These examples present just a small picture of Raman theory and application in biotechnology. All of Raman’s advantages have propelled it to be a mainstream analytical testing tool. From product development to market launch and at every stage in between, Raman provides additional layers of information and will only continue to improve to meet the evolving needs of the biotechnology industry.
If you are interested in more in depth information on this topic, please view my Fundamentals Series presentation, “Raman Applications in Biotechnology” for Pharmaceutical Manufacturing Magazine. From the presentation, you will learn additional details about applying Raman across the product lifecycle as well as a review of cutting-edge Raman technologies and applications that have developed over recent years.