POC molecular diagnostic header POC molecular diagnostic header

Thermal Cycling for a Point-of-Care Molecular Diagnostics Instrument

Helping deliver rapid and accurate point-of-care diagnoses.

Molecular diagnostic solutions (MDx) help physicians treat infectious diseases sooner and with more precision - improving healthcare to save lives. When a major molecular diagnostic OEM needed to develop a thermal cycler as part of a new point-of-care MDx device, they turned to Plexus to develop a custom solution. See how Plexus supported the successful commercial introduction of MDx solutions to enable better healthcare outcomes.

Solution Spotlight

CUSTOMER:

Major Molecular Diagnostic OEM

PRODUCT:

CLIA-Waived, Point-Of-Care Molecular Diagnostic Instrument

SOLUTIONS:

  • DESIGN AND DEVELOPMENT
  • SUPPLY CHAIN SOLUTIONS
  • NEW PRODUCT INTRODUCTION
  • MANUFACTURING

Supporting life-saving clinical answers without the wait.

In healthcare, every second counts. Patients, and their families, are counting on doctors to make critical, life-saving diagnoses and decisions every hour of every day. There’s no room for error. And there’s no time for waiting.

Molecular diagnostic (MDx) solutions are critical technologies aiding healthcare providers in making diagnoses and decisions. These solutions combine lab testing with the precision of molecular biology to improve the accuracy and speed of detecting microbial pathogens and analyzing a patient’s genes. MDx technologies quickly perform DNA-level detective work, separating a DNA strand and quickly copying it millions – or even billions – of times so scientists can study it in detail. The insights provide doctors the essential information necessary to make informed diagnostic and therapeutic decisions.

MDx technologies are quickly becoming an essential aspect of life-saving interventions and therapeutics around the world. These revolutionary solutions unlock the answers doctors and patients need, when they need them most.

Democratization of PCR is driving the healthcare industry forward.

A thermal cycler is a device traditionally used in laboratories to amplify segments of DNA in a series of cyclical temperature changes that drive the Polymerase Chain Reaction (PCR). It’s a process that’s fundamental to genetic testing and identifying infectious agents such as SARS-CoV-2, the virus causing COVID-19.

DNA tests incorporating PCR dominate the MDx industry, representing an approximately $10 billion market forecast to grow at a 9% compounded annual rate. Point-of-care MDx solutions are the fastest-growing segment of this market providing physicians the ability to get results in non-laboratory settings such as the physician’s office and home-care settings, without waiting for centralized labs to return results. And while a PCR-based point-of-care MDx instrument requires many subsystems, the thermal cycler is critically important to delivering reliable results.

While PCR is common in lab settings, point-of-care MDx solutions require complex integrated workflow solutions to reduce the need for human handling, which can be a source of potential contamination and error. These integrated workflow systems usually include custom and proprietary consumable devices, often called cartridges, that house the assay and require non-standard thermal cyclers to drive PCR.

DNA tests incorporating PCR dominate MDx solutions, a ~$10B market that’s forecast to grow at a 9% CAGR.

A challenging thermal cycler design.

All facilities in the United States that perform laboratory testing on human specimens for health assessment, or the diagnosis, prevention, or treatment of disease, are regulated under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). The customer’s need was for a device suitable to obtain a CLIA waiver; requiring the device to be highly reliable, accurate and designed to preclude risks of user error in a point-of-care setting.  This basic need brought with it many considerations and challenges in designing and manufacturing this PCR-based, point-of-care MDx instrument and the thermal cycler, which is critical to its function.

Custom thermal cycler design can present a host of technical challenges, including: control system design to provide rapid and repeatable cycling, mechanism design to tolerate varying cartridge positions and thermal interface design to ensure efficient and repeatable heat transfer.

In addition to the normal challenges of designing a custom thermal cycler, this project presented some unique complications. First, we needed to drive PCR in a custom-designed cartridge, not the universal plates and tubes normally used for PCR. Such custom cartridges provide a logical route to sample-to-answer, CLIA-waived reliability and performance standards, but they often create challenges in system design. Specifically, cartridges typically have irregular polymer surfaces that are less than ideal for thermal interface with a thermoelectric cooler (TEC), the most commonly used component for heating and cooling a PCR chamber. Furthermore, cartridges are typically designed with multiple PCR chambers to enable analysis of multiple sample and standards in parallel. This was the case here, which meant we needed to drive fast, parallel thermal cycling across three sample chambers, while still leaving PCR chambers accessible for real-time monitoring by multi-channel fluorescence detection.

A custom thermal cycler solution.

Fast and precise thermal cycling. Multiple parallel sample chambers in a single cartridge. A less-than-ideal thermal interface. Those were the challenges our team had to solve. And our solution needed to drive successful, reproducible PCR that supported the customer’s full point-of-care MDx instrument solution. We had to ensure results were accurate every time, all the time.

To accomplish these objectives, Plexus leveraged our experience with various thermal management and control applications. We analyzed the entire thermal cycler, including the cartridge system, and identified the critical considerations of the control system, the cartridge mechanism and the thermal interface. We tested and evaluated a variety of design options to determine which would best support the thermal cycling requirements for the customer’s application. Plexus chose the most reliable, consistent performing design to produce the required results, while balancing critical product lifecycle variables such as the cost of raw materials, development timeline, manufacturability, serviceability and component lifetime.

This completely custom system supports the customer’s consumable cartridge design, while leveraging TECs from trusted suppliers to enable scale and reliability.

Our design ensured the system can accurately, reliably and quickly:

  • Minimize surface roughness anomalies of cartridges to improve thermal interface prior to sample analysis
  • Accommodate gross cartridge curvatures and/or surface anomalies of 150µm in magnitude
  • Dissipate heat to support the TEC’s ability to drive fastest possible thermal cycling between ambient and 95°C
  • Ensure sample-to-sample thermal uniformity between cartridge chambers as well as unit-to-unit reproducibility

Our final design balanced the many requirements and tradeoffs to deliver thermal cycling capabilities with repeated cycling between typical high and low temperatures used in PCR. The Plexus solution provides uniform, repeatable results across the board — between cycles, PCR reaction chambers and relative to set points — and precise thermal cycling every time.

Plexus leveraged industry-leading design and supply chain capabilities, along with expertise gained through prior experiences in thermal interfacing and management, to develop thermal cycling capabilities specific to the customer’s consumable and application requirements.

Speed is critical in a competitive market.

In a market as competitive and fast-moving as molecular diagnostics, the time-to-market from concept to new product introduction is critical to success. Choosing the right design and manufacturing partner can make the difference between delivering improved patient outcomes and business success versus running over budget and launching late.

Our customer chose Plexus to provide a full array of thermal cycling expertise, from design through manufacturing, based upon our proven success in delivering a broad range of similar systems to market.

This thermal cycler is one of many subsystems within the complete instrument solution that our customer entrusted to the Plexus team. With our focus on life sciences industry leading integrated engineering capabilities, breadth of experience and global manufacturing capabilities, the customer knew it could count on Plexus to provide an exceptional product, with a focus on achieving achieve zero defects and perfect delivery. And the clinicians and patients who rely on fast, reliable answers at the point-of-care are able to get the life-saving diagnoses and treatments they need.

Contact our global Healthcare and Life Sciences team.

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