Translating Laboratory Performance to Your Point-of-care Device

This transition presents major technical challenges. A common example is the performance of magnetic beads on-cartridge. For all practical purposes, magnetic beads are sample preparation for assay development. With annual sales in excess of $1 billion, magnetic beads enable kits for virtually every sample preparation workflow in the industry, and often the bead-based assays are the gold standard. Yet when bead-based assays transition to sample-to-answer cartridges, their performance often degrades dramatically.

Magnetic beads are the standard for sample prep

Magnetic beads have been a key driver of progress in the life science industry for decades. Beads improve analytic assay performance by enabling analyte extraction, purification and concentration. Major applications include cancer biomarker discovery, molecular diagnostics, and sequencing. They are a convenient tool for laboratory researchers, who can develop assays using conventional laboratory tools like PCR tubes, rotators, magnetic racks and pipettors.

Magnetic beads come in different compositions, sizes and shapes and make the sample prep process in assay development fast and efficient. Coupling magnetic properties with specific ligands in magnetic beads allows the separation and purification of cells, proteins, nucleic acids, and other molecules in a highly efficient and specific manner.  For isolation of certain cell types or proteins, magnetic beads can be conjugated with specific antibodies. Magnetic beads are highly versatile, because the functional chemistry can be easily modified or optimized for a specific purpose. Scientists frequently invest time and energy testing and their magnetic bead selection to ensure reproducibility and efficacy of their laboratory-developed protocol.

The case for porting bead-based protocols to cartridges

Meanwhile, multiple billion dollar-plus markets are transitioning to sample to answer solutions. Sample-to-answer systems reduce time-to-result and the total cost of system ownership. Laboratory system vendors are porting existing workflows to cartridge formats and upstarts are developing fieldable systems to address new use cases. Some applications where porting the bead-based assay to cartridge format would offer a profound advantage to developers include multiplexed-immunoassays, POC molecular diagnostics and sequencing. But in order to compete, these new, fast, and compact sample-to-answer systems will need to perform as well or better than their laboratory counterparts.

Often, developers of these sample-to-answer systems are starting with a working laboratory assay that they are porting to a cartridge. Developers seek to expand their testing menus on current platforms in order to expand revenue streams and stay competitive. They know the fastest way to develop new protocols is to leverage their back-catalogue of protocols and indications. These laboratory assays often make use of magnetic beads, and the last thing developers want to do is replace their proven reagents, because a change in reagents implies that the assay will need to re-validated.

One example where demand to move to cartridge-based formats is high includes sample and library preparation workflow upstream of sequencing. This part of the workflow involves highly manual protocols that use magnetic beads in multiple steps (e.g., size selection and post-PCR cleanup). The natural approach for developing a sample-to-answer version of the assay would be to simply “put the magnetic beads in cartridge and automate the protocol.” Easy, right?

Unfortunately, this strategy too often results in disastrously expensive projects and poorly performing products. Yes, it would be ideal to use the same magnetic beads in both the benchtop and microfluidic environments as doing so eliminates the risk of having to re-implement the bead chemistry in a new device. Yet beads do not perform on cartridges as laboratory scientists might expect.

Beware of bead-based assay performance on-cartridge

The ability to port bead-based assays onto microfluidic cartridges would dramatically streamline the transition of lab-based assays into sample-to-answer formats. The problem is that this transition is deeply problematic.

Having learned for ourselves in a recently-published application note, we found that magnetic bead assays are profoundly unreliable in a microfluidic format and their performance is compromised in a number of ways. It is often only late in cartridge integration and testing that developers discover that the limit of detection is now higher, test variance is wider, and the time-to-result is too long.

Experienced system developers know how hard porting laboratory-based assays to a cartridge can be, and will warn you of the time and expense it will require. Fortunately, there are ways to identify and mitigate the risks. To learn more about the specific challenges of porting assays to cartridges, check out our blog entitled, Are you ready to put your sample prep on a cartridge?