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USING CIRCUIT BOARD MATERIALS FOR THERMAL CONTROL IN MEDICAL DIAGNOSTICS Circuit board materials and structures can be cleverly adapted to become thermal control components for medical diagnostic systems. (PCB) fabrication techniques simplify design by providing an easily customizable source from which heat (and cooling) can be generated, distributed, measured and dispersed. Through iterative simulation and physical prototyping, PCB techniques can rapidly advance designs for precision thermal management in the tight spaces and dynamic climates of microfluidic cartridge architectures. Conveniently, PCB fabrication techniques also easily scale from rapid prototyping to mass production, speeding design transfer. Key Tech has employed PCB techniques for thermal management whether or not there is already a need for electronics on a diagnostic cartridge, and these PCB-based thermal managers can live on the cartridge or near it on the instrument. We’ve dramatically shortened thermal design time using PCB-based modules, and solved some unique thermal management challenges along the way.

USING CIRCUIT BOARD MATERIALS FOR THERMAL CONTROL IN MEDICAL DIAGNOSTICS KEYTECHINC.COM 2 INTRODUCTION

In Vitro Diagnostic (IVD) assays almost applications with fast thermal cycle times, but they will always require some type of thermal control increase design scope and the unit cost of cartridges. of a fluidic sample. Heating may be needed to assist with lysis during sample prep, thermocycling is At Key Tech, we have been leveraging Printed Circuit required to amplify DNA, and certain detection methods Board (PCB) fabrication techniques to create custom thermal control components, where the thermal masses require the sample to be at a precise and heat conduits are built right into the PCB. PCBs when measurements are taken. Many IVD systems are constructed by alternating layers of electrically are also using microfluidic lab-on-a-chip technologies conductive copper traces and insulating substrates like to increase speed, reduce device size, and bring these FR4, a common class of glass fiber/epoxy composite instruments out of the lab and closer to the point of used in PCB’s. These same materials that are used care. Thermal control in these microfluidic applications for their beneficial electrical properties are also good thermal conductors and insulators, so they are optimal can present many challenges, including: for creating thermal control components. There are a number of benefits with using this approach: • Maintaining highly precise

• Maintaining tight temperature uniformity, • Leveraging a common fabrication technique especially when there are multiple zones at allows for quick prototyping and also easily different temperatures in close proximity scales up to mass production. • Achieving fast rise and cool times, • Thermal management components embedded in especially while maintaining temperature uniformity the PCB can be customized over a wide range • Accurately measuring temperature on of shapes and sizes. a small scale where traditional are too • Multiple components and functions large and would influence the measurement can be built into the same PCB (e.g., power and control circuitry, for heat So how do you quickly and economically design generation, thermistors or RTDs for temperature thermal control for microfluidic IVD applications with measurement, electrochemical detection circuitry, etc.). these challenges? For macro heating applications, • The low thermal mass compared to some cartridge heaters embedded in blocks of metal alternative approaches allows for faster contacting the vials or cartridges containing the sample temperature cycling. will do the trick, but in small scale applications, the precise heat control required and the small space Using this approach can be especially beneficial if the limitations usually make this approach impractical. Thin microfluidic cartridge or device already requires a PCB film heaters can work in some cases, but customizing for other functions. Because of the other benefits listed above, this approach can also be beneficial even if a these heaters to challenging applications can be tricky. PCB isn’t already required for other functions. Custom heating elements built into the microfluidic cartridges can also be a promising option, balancing Key Tech has designed a number of thermal control heat management requirements with cartridge cost components from PCBs over the years. Below is a guideline for designing these types of applications targets. We’ve worked on applications where traces based on our experience: of metals like platinum are bonded to microfluidic chips to create custom heating and temperature sensing elements. These implementations allow for total customization and may be required for demanding

USING CIRCUIT BOARD MATERIALS FOR THERMAL CONTROL IN MEDICAL DIAGNOSTICS KEYTECHINC.COM 3 HEAT GENERATION

Generating heat is one of the most basic Another approach is to use copper traces to create functions of thermal control. The simplest way a inside the PCB. Even though to generate heat on a PCB is by soldering a power copper is very conductive, it still has some resistance, to it. Resistors generate plenty of heat, but so a long thin trace (e.g., 10-15cm) can be used to because they are a point source, the PCB design must form a heating element within the PCB (Figure 3). sufficiently spread the heat out. Otherwise a metal This approach may not generate as much heat as a heat spreader may need to be attached. Custom dedicated resistor, but it can provide a more uniform elements like metal heat spreaders are typically heated area without the need for a separate heat more useful in an instrument than on a microfluidic spreader. Additionally, since the trace that creates cartridge. Figure 1 shows a cross section of a PCB illustrating how this approach can be implemented. the heat is formed as part of board fabrication and A power resistor is placed on the bottom of a PCB no additional components are needed, the heating and then Vertical Interconnect Access holes (VIAs) element comes “free” as part of the design. This is transfer the heat to the top side where a copper plane very appealing for on-cartridge heating applications, spreads the heat out over the desired area to maintain especially if a PCB is already needed in the a uniform temperature. Figure 2 shows a PCB cartridge for other functions. Even if the cartridge where this approach was implemented to allow for 64 doesn’t already require a PCB for other functions, independently heated zones. for demanding applications it may still be worth

Copper plane on Vias for heat transfer considering integrating a PCB into the microfluidic top surface to through the PCB spread heat cartridge just to implement this approach. It may be Copper more cost effective than designing custom heating

FR-4 elements onto the cartridge (e.g., layering platinum heaters onto the cartridge components). Resistor

V+ for resistor Ground plane also Winding a trace of facilitates heat transfer copper across the heated zone allows for a long trace length Figure 1: Construction of PCB with a resistive heater on the bottom and copper top plane to spread heat on the temperature controlled top side Zones formed by copper planes isolated by FR4

Figure 3: Trace layout of a heater made with a thin winding trace of copper

Peltier elements can create heat and can also cool, so if active cooling is also needed, a Peltier can be Figure 2: Thermal Management PCB with 64 independently connected to a PCB. More details on Peltier elements controlled temperature zones heated by resistors attached to the are discussed in the cooling section below. underside of the PCB

USING CIRCUIT BOARD MATERIALS FOR THERMAL CONTROL IN MEDICAL DIAGNOSTICS KEYTECHINC.COM 4

In order to provide accurate closed-loop much as possible. The low thermal mass of miniature temperature control, the temperature of can also allow for fast response times, the thermal control component must be which can be especially helpful when measuring measured. A thermistor soldered onto a PCB is one transient applications. of the simplest methods for measuring temperature. Thermistors can provide precise measurement at Another challenge with verifying temperature temperatures up to 150C. Like a power resistor, a performance during development is to obtain accurate thermistor provides a point-source measurement, surface temperature measurements. Non-contact so the design must accurately relate the thermistor infrared (IR) measurement can be a helpful tool; while temperature to the temperature of interest. The goal in IR cannot give a highly accurate absolute temperature diagnostics is to control the fluid sample as it proceeds measurement (+/- 2C typically), it can provide through assay steps on the cartridge, so the thermistor very accurate differential measurement of surface must measure a temperature as close as possible to temperature (within a few tenths of a degree C). For the fluid sample temperature. Offset temperatures this reason IR sensors can be especially helpful between thermistors and the fluid sample can when verifying the temperature uniformity of a heated sometimes be successfully characterized (e.g., sample surface. When using the IR approach you need line-of- temperature is 1C less than measured thermistor sight to the surface being measured, and the emissivity temperature at target fluid temperature of 95C). This should be relatively constant over the surface being requires iterative modeling, design and testing to measured. Changes in materials, coatings and surface generate sufficient data for a repeatable and accurate textures over the surface of interest can change the offset relationship. emissivity so that a reliable differential measurement can’t be obtained. However, some forethought in the Another common temperature measurement design to ensure constant emissivity over surfaces challenge is verifying during development that the of interest could allow IR sensing to be used and temperature being measured is accurate within the simplify verification. To obtain line of sight to the required tolerances. This requires an independent surface, certain components that aren’t critical to the measurement outside the design, and you can thermal functions of the device could be designed to be paradoxically influence the temperature you are trying removable. Alternatively a microfluidic cartridge can be to verify. Miniature calibrated thermocouples can designed such that a “thermal verification” configuration provide measurements in the small spaces available can be made with portions cut away to allow a view of in a diagnostic system, and perform well over a wide internal surfaces where thermal uniformity is critical. range of temperatures. It is nearly impossible to eliminate the effect of the measurement technique influencing the measurement, but the small size of miniature thermocouples helps reduce the effect as

USING CIRCUIT BOARD MATERIALS FOR THERMAL CONTROL IN MEDICAL DIAGNOSTICS KEYTECHINC.COM 5 HEAT TRANSFER

Managing heat transfer is another critical and specifying that the hollow cores of the VIAs be function. Proper heat transfer management ensures filled with solder. that thermal zones will be sufficiently uniform and also sufficiently isolated from each other. In a PCB, you can manage heat transfer by using its thermally conductive copper layers to facilitate heat transfer, and its insulating substrate layers to prevent it. Table 1 below lists approximate thermal conductivities of components used in PCB fabrication to manage thermal control. Copper and aluminum can be used to facilitate heat transfer and FR4 can be used to prevent it (Figure 4). Thermal grease and epoxy can be used to improve heatflow between the PCB and external components like aluminum heat spreaders The thermal conductivities of grease and epoxy may Figure 4: Cross Section of a PCB with VIAs and internal traces seem low, but significantly reduce the effect of the thermal contact resistance. Thicknesses of the copper and insulating layers can also be varied to achieve the desired goal. Table 1 : Typical Thermal Conductivities of Common Materials Thicker copper layers will increase lateral heat flow, while thicker insulating layers will increase thermal resistance through the thickness of the PCB in areas MATERIAL (W/m*K) where VIAs are not present.

Copper 400 There is a practical limit to the copper thickness that can be specified when using standard fabrication Aluminum 150 techniques (typically the max is 4mils, or 0.1mm). If the thermal uniformity still isn’t sufficient with FR4 0.25-0.35 - through plane (z) 0.8-1.0 - in plane (x-y) the maximum practical copper thickness, bonding metal heat spreaders onto the PCB can work in Thermal some applications. It is important to ensure that 1-8 Grease/Epoxy a good thermal epoxy/grease is used or that the heat spreaders are soldered/brazed to the PCB to Lateral heat transfer in the x and y directions can be ensure good thermal contact. Otherwise varying controlled by the design of the copper layers in the thermal contact resistances may result in inconsistent PCB. Large planes of copper can be used to spread performance. Figure 5 below illustrates how a heat heat out to create areas of uniform temperature, and spreader can be integrated with a PCB to provide traces of copper can be designed to direct heat from uniform heating when using copper on the PCB alone one location to another on the PCB. Remember, will not provide sufficient thermal uniformity. however, that the traces used for a PCB’s first Aluminum Heat purpose, electrical routing, will also conduct heat. Thermistor Resistor Spreader Account for them in the thermal design and rout them in a way that contributes to the desired thermal profile. For example, if a PCB has multiple thermal zones PCB that must be kept at separate temperatures (e.g., for PCR), electrical traces for resistors, thermistors and other features coming from each zone should avoid crossing into the other zones if possible to minimize the thermal cross talk between zones. Heat transfer in the z direction through the thickness of the PCB is facilitated by adding VIAs, which are the same metal plated holes commonly used to electrically connect different layers of a PCB. A number of methods can be used to improve the heat transfer of VIAs, including using arrays of densely Figure 5: PCB with Resistive heaters and thermistors embedded packed VIAs, maximizing the VIA plating thickness, in aluminum heat spreaders

USING CIRCUIT BOARD MATERIALS FOR THERMAL CONTROL IN MEDICAL DIAGNOSTICS KEYTECHINC.COM 6 DESIGN ANALYSIS

Achieving precision thermal performance allow for more detailed exports of PCBs from ECAD requires iterative analysis to predict software to MCAD software so the work of recreating performance and determine the effects of the details of the PCB design in MCAD software for changing design variables as the design FEA analysis can be simplified. Figure 6 illustrates a matures. Analyzing the design of PCB-fabricated hybrid approach where a detailed PCB was exported thermal components is fairly straightforward, into MCAD, but some of the internal traces were because heat transfer within the PCB is governed combined into a single central custom non-isotropic by conduction. For simple components, hand material to simplify the model. This particular FEA is calculations suffice for calculating heat transfer and analyzing the temperature uniformity of a central cold temperatures. Using the thermal circuit approach, zone when all surrounding zones are heated. each direction of the PCB can be considered a “composite wall” consisting of copper and the insulating substrate. Specific thermal resistances can be calculated for the x, y and z directions based on the area of copper and area of insulating substrate Power in the cross section of the board perpendicular to Resistor each direction. The calculated thermal resistances can then be used in thermal circuit hand calculations to estimate heat flow and general temperature Symmetry Planes differences between different sides of the PCB or Heated Outer Zones different zones on the PCB. These quick, rough calculations can be helpful early on in the design process when creating and iterating on simple breadboard prototypes.

For a more precise analysis of temperature uniformity, or when performing transient analysis, it is usually Central Cold Zone preferable to use FEA (Finite Element Analysis) modeling. Because most of the heat transfer within Figure 6: FEA model of a 9-zone PCB based thermal control the PCB is governed by conduction, complex CFD component using 2-plane symmetry for simplicity (Computational Fluid Dynamics) modeling isn’t usually needed and standard FEA using SolidWorks While FEA can be used to inform the design, Simulation or similar software can provide good confirmatory testing should be done to verify that the results. For a quick simple model, specific thermal predictions match reality. There are many vendors resistances for the x, y and z directions can be that offer prototyping and quick turn PCB fabrication calculated by hand as described above and a custom services, which allow for rapid design iterations. non-isotropic material can be created in the FEA An FEA can be performed model with the unique thermal resistances specified to help generate an initial for each direction. The PCB can then be modeled design, and a week later as a simple rectangle and an FEA can be quickly the design is fabricated performed. If you have access to FEA software and and back in-house being understand the fundamentals well enough to establish tested. The FEA can then an accurate yet simple model, it is usually faster and be refined to match the more thorough to go right to simple FEA modeling real world performance rather than performing hand calculations. of the initial prototype and changes to improve For PCBs with complex trace routing and multiple performance can be temperature zones, the simplified modeling approach evaluated with a more may be too crude, and better results can be had by accurate FEA model that’s more fully detailing the model with the geometry of the informed by the testing. copper traces. It can take some time to fully create The cycle can then be a model of the PCB, but FEA best practices can be continued with iterations used to simplify the modeling and analysis (e.g. use in quick succession until Figure 7: Thermal component symmetry, simplify geometry, ensure proper mesh size the performance meets development cycle using FEA and refinement, use appropriate boundary conditions the requirements (Figure 7). modeling etc.). Additionally, a number of Electrical CAD (ECAD) to Mechanical CAD (MCAD) connectors can

USING CIRCUIT BOARD MATERIALS FOR THERMAL CONTROL IN MEDICAL DIAGNOSTICS KEYTECHINC.COM 7 DIFFERENTIAL THERMAL EXPANSION

Another important consideration to keep ingredients can’t contaminate the grease, and properly in mind is the effect of differences in containing the grease in the assembly. coefficient of thermal expansion (CTE) of the materials being used. FR4, a common Table 2: Thermal Expansion Coefficients of Common Materials. PCB substrate material, has a similar in-plane (x-y) Coefficient of Thermal Expansion (K-1) expansion coefficient to that of copper. However, as MATERIAL seen in Table 2, it is an anisotropic material due to its Copper 1.7X10-5 glass fiber/epoxy resin composite, so it has a higher Aluminum 2.2X10-5

through-plane (in the z-direction) expansion coefficient -5 FR4 7.0X10 - through plane (z) than copper. In some cases, this could affect heat 1.2-1.4X10-5 in plane (x-y) transfer characteristics, but typically the bigger Thermal 2.0-5.0x10-5 (for epoxy) concern is that the stresses imparted could damage Grease/Epoxy the PCB (e.g., break traces) if it must operate over extreme temperature ranges or if it must withstand a high number of cycles. Thermal expansion must also COOLING be considered when bonding components like heat Many diagnostic applications also spreaders onto a PCB. The coefficient of expansion require active cooling to maintain proper of the heat spreader material as well as any type of temperature or to perform temperature epoxy used to bond the spreader to the PCB must be cycling. Passive or forced air convection is the considered, as significant mismatches could cause simplest approach for removing heat from PCB- the bondline to break and result in inconsistent heat fabricated thermal control systems. The fairly low transfer. If analysis shows that the materials or thermal mass of these PCB-based systems can temperatures required are pushing the limits of CTE make this approach more feasible than for other mismatch, thermal grease may be a better choice approaches with larger thermal mass. Passive or forced air convection relies on ambient air than bonding with epoxy. temperature, so cooling performance changes with changing ambient temperature. However, you can Additional fastening features will be needed to never cool below the ambient temperature using this secure the PCB to the heat spreader, but because approach. So, for example, if the application requires the thermal grease remains fluid it can be more cooling from 95-60C, passive or forced air convection tolerant of the expansion and contraction of the PCB may be practical, but if the temperature must be brought and heat spreader materials. Care should be to 40C in an instrument enclosure, it would not. taken to ensure that the grease selected will not migrate over time and result in increased thermal When cooling requirements demand a solution resistance. This can be prevented by selecting beyond convection, a Peltier element (aka thermoelectric cooler, or TEC) can be employed. grease of the proper viscosity, ensuring that liquid assay Peltier elements usually aren’t components that can

USING CIRCUIT BOARD MATERIALS FOR THERMAL CONTROL IN MEDICAL DIAGNOSTICS KEYTECHINC.COM 8 be integrated directly onto a PCB, but a PCB can Resistors and thermistors on be integrated around a Peltier element to allow for PCB embedded in active cooling as seen in Figure 8 and Figure 9. A heat spreader Peltier element can cool below ambient and remove more heat than pure convective cooling may be able Peltier to do on its own. Additionally, a Peltier element can produce heat when the current flow is reversed. The ability to heat and cool can allow for higher precision temperature control and faster thermal cycling than a design that uses convective cooling with Figure 9: Peltier module integrated with PCB mounted resistive resistive heating. You pay for this benefit with added heaters for active heating and cooling complexity. Space must be found to integrate the Peltier element, which can be difficult in miniaturized may be simpler to move the sample between different applications. Peltiers also require heat sinking and zones that are held at different constant temperatures usually ducting and airflow to remove heat from the vs. thermal cycling in place. This can be achieved Peltier. Since Peltier elements are only 10-15% through approaches like digital microfluidics or by efficient, they generate a significant amount of heat forming microfluidic channels on the PCB surface. on the hot side compared to the heat removed on The latter approach can be performed by adhering a the cold side. For these reasons, it is usually best molded plastic part with channels to the PCB and then to ensure that alternative approaches have been using common microfluidic pumping techniques to exhausted before going down the path of integrating move the fluid between zones. Peltier elements. Sometimes, however, Peltiers are the only practical method if active cooling is needed. Aluminum CONCLUSION Heat Spreader Thermal design for diagnostic systems can be PCB challenging, particularly when assay design requires rapid thermal cycling, or when multiple proximate zones need to be maintained at different temperatures. Designs must simultaneously meet requirements for Peltier element tight temperature precision, temperature uniformity across a sample fluid, real-time temperature measurement and more, all within the tight spaces Heat sink defined by the cartridge and instrument architectures. Using PCB fabrication techniques can offer some significant benefits over other more traditional approaches. Key Tech has designed dozens of Figure 8: Cross section of Peltier element integrated with a PCB and diagnostic instruments for clinical, industrial, and heat spreader for active heating and cooling consumer applications, and we’ve learned how and When neither convective cooling nor a Peltier element when to use these PCB techniques, and when to use seem ideal for the application, it may be worth other solutions as well. Contact us with your thermal considering alternative approaches that may not have design challenges, especially the tough ones. as stringent cooling requirements. For example, when performing thermal cycling for DNA amplification, it

USING CIRCUIT BOARD MATERIALS FOR THERMAL CONTROL IN MEDICAL DIAGNOSTICS KEYTECHINC.COM 9 Since 1998, Key Tech has been transforming complex technologies into intuitive products. We design and develop medical, industrial and consumer products using novel sensors, wireless, ultrasound, microfluidics, optics and automation. Our uniquely personal approach attracts industry leading global companies, as well as innovative startups, to our Baltimore Headquarters. The Key Tech team of interdisciplinary scientists, engineers and designers take technologies into new applications, keeping your development pipeline fresh.

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