Inline, Online, Atline, or Offline: How Solid-State Raman Analyzers can be Adapted for Any Point of Need

by | Sep 15, 2021 | Raman 101

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Updated March 14, 2023.

Inline, online, atline, and offline: these are the four primary classes of measurement used in process analysis. Modern process analytical technology (PAT) needs to be reliable and accurate. But perhaps most importantly, PAT needs to be adaptable enough to analyze the process regardless of location and interface. This article will help define the four classes of process measurement and demonstrate how a solid-state Raman system can deliver quick, consistent, and accurate compositional data whether you are sampling inline, online, atline, or offline.


Defining Process Production

According to Kate Brush, Brenda Cole, and Jim O’Donnell, of, Process Production or Process Manufacturing can be defined as “a production method that creates goods by combining supplies, ingredients or raw materials using a formula or recipe. It is frequently used in industries that produce bulk quantities of goods, such as food, beverages, refined oil, gasoline, pharmaceuticals, chemicals, and plastics.” (Brush, et al. 2020) In practice, this definition implies that equipment and methods used in ‘process’ applications must be robust, highly tested, and tightly controlled as they directly contribute to the final product quality.


Advantages of Solid-State Raman

Before we dive into the different classes of process analysis, let’s discuss why solid-state Raman systems are particularly well-suited for process measurement. Solid-state Raman systems, like the stable, compact MarqMetrix® All-In-One (AIO), have very few moving parts and are ideal for continuous process monitoring and routine lab analysis. As a result, these systems can be placed at any point of measurement. The AIO can take advantage of numerous, application-specific sampling interfaces that can be changed in seconds, without the need for recalibration. This makes it easy to find an interface that will work for sampling inline, online, atline, or offline in any industry. For each of the classes of measurement defined below, MarqMetrix can provide a Raman sample interface designed for that specific point of need.

Disclaimer: The interfaces that we discuss in this article are adaptable to a wide variety of applications. We may highlight certain probes in conjunction with a specific form of measurement, but that does not mean it is the only type of measurement that the probe can be used for. Nor does it mean that there is only one probe that can be used for each type of measurement. Each probe has a variety of applications. Please keep this in mind as we discuss each class of measurement and sampling interfaces.


Inline Measurement

Inline measurement involves placing a probe or sampling interface directly into or inline with the process or product flow. Usually, this involves placing a probe in a flow system or into a bioreactor. Inline measurement allows customers to measure the product constantly and continuously without removing the Raman “probe” or samples from the process. Some customers elect to use inline Raman measurement at several different locations in parallel to determine product consistency throughout their process.



MarqMetrix has several probes designed specifically for inline sampling. Our original BallProbe® sampling interface is probably the most well-known and comes in a variety of sizes, materials and lengths. One example that is particularly well-suited for inline measurement is the BioReactor BallProbe® that features a 12mm outside diameter and standard Pg13.5 fitting to easily integrate with industry-standard bioreactors. The BioReactor BallProbe is designed to be fastened directly into a bioreactor for continuous compositional measurements during a bioprocess.


Online Measurement

Online measurement is very similar to inline, though there are some key differences. Online analysis, like inline, measures the process without taking samples to a separate location. However, it usually involves separating some of the product from the main process line and performing measurements on just a portion of the product. Often this is done by adding a sampling loop where you can analyze the process using an online Raman interface. The diverted sample can be re-introduced to the process stream, or wasted, depending on the application.



While there are many MarqMetrix probes that can be used for online measurement, the most prominent example is the FlowCell. The FlowCell takes MarqMetrix spherical sapphire lens technology, made famous by the BallProbe, and incorporates into a housing designed to be integrated into a flow system for effective sampling of a flowing sample. For online measurement, simply divert a portion of the product through a FlowCell and sample continuously without process interruption.


Atline Measurement

When we discuss atline and offline measurement, there is a key differentiator that stands out right away. Inline and online measurement both offer the ability to continuously measure the process in real-time. Atline and offline measurement usually requires manually collecting a sample or samples and performing analysis separate from the process. We can further differentiate atline and offline measurement by the distance between the production facility and the analytical measurements being performed. When measuring atline, analysis is still completed at or near the process. However, that analysis is being done apart from the process after a sample has been removed for testing.



For atline measurement, we recommend a versatile probe that can handle a wide range of sample types, including liquids, solids, powders, pastes, and gels. The standard BallProbe is a perfect probe for this purpose. The spherical sapphire lens enables TouchRaman sampling: when the lens of the probe is in contact with the sample, you are accurately and reproducibly collecting data-rich compositional information of the atline samples.


Offline Measurement

Offline measurement involves the most physical separation between the process and analysis of the sample. Similar to atline measurement, offline measurement involves removing an analytical sample from the process. But instead of analyzing the sample at the production facility, offline measurement involves taking a sample, or sometimes multiple different samples, to a formal lab setting for analysis.



The MarqMetrix All-In-One is engineered to produce effective measurements in a lab or process setting. But for multi-user benchtop facilities where you might perform high-volume offline measurements, we strongly encourage you to consider the Walkup All-In-One® or WAIO. WAIO is a certified Class-I laser device, safe for use in multi-user facilities. The height-adjustable tray is perfect for sampling well-plates, vials or other vessels. In addition to being easy to use for offline measurement, the WAIO also maintains the stable and reproducible, high-performance compositional analysis that you expect from MarqMetrix solid-state Raman systems.


Measurement Anywhere, Anytime

No matter where you decide to perform measurements in your process, MarqMetrix has a Raman system and sampling interface that will improve your compositional measurements. Modern, solid-state Raman systems allow for flexibility in placement, interface, and sample type without sacrificing performance. For the best results and performance, it is imperative to choose the correct sampling interface for each of your applications. If you need help determining the best Raman system for your application, reach out to one of our experts by clicking here.


Brush, K., Cole, B., O’Donnell, J. What is process manufacturing? Process Manufacturing Definition, TechTarget, February 2020.



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