BACKGROUND

The embodiments described herein relate to devices and methods for molecular diagnostic testing. More particularly, the embodiments described herein relate to heaters and methods of heating a sample volume to amplify a nucleic acid in a molecular diagnostic testing device.

There are over one billion infections in the U.S. each year, many of which are treated incorrectly due to inaccurate or delayed diagnostic results. Many known point of care (POC) tests have poor sensitivity (30-70%), while the more highly sensitive tests, such as those involving the specific detection of nucleic acids or molecular testing associated with a pathogenic target, are only available in laboratories. Thus, molecular diagnostics testing is often practiced in centralized laboratories. Known devices and methods for conducting laboratory-based molecular diagnostics testing, however, require trained personnel, regulated infrastructure, and expensive, high throughput instrumentation. Known high throughput laboratory equipment generally processes many (96 to 384 and more) samples at a time, therefore central lab testing is often done in batches. Known methods for processing test samples typically include processing all samples collected during a time period (e.g., a day) in one large run, resulting in a turn-around time of many hours to days after the sample is collected. Moreover, such known instrumentation and methods are designed to perform certain operations under the guidance of a skilled technician who adds reagents, oversees processing, and moves sample from step to step. Thus, although known laboratory tests and methods are very accurate, they often take considerable time, and are very expensive.

There are limited testing options available for testing done at the point of care (“POC”), or in other locations outside of a laboratory. Known POC testing options are often single analyte tests with low analytical quality. These tests are used alongside clinical algorithms to assist in diagnosis, but are frequently verified by higher quality, laboratory tests for the definitive diagnosis. Thus, in many instances, neither consumers nor physicians are enabled to achieve a rapid, accurate test result in time to “test and treat” in one visit. As a result, doctors and patients often determine a course of treatment before they know the diagnosis. This has tremendous ramifications: antibiotics are either not prescribed when needed, leading to infections; or antibiotics are prescribed when not needed, leading to new antibiotic-resistant strains in the community. Moreover, known systems and methods often result in diagnosis of severe viral infections, such as H1N1 swine flu, too late, limiting containment efforts. In addition, patients lose time in unnecessary, repeated doctor visits.

Moreover, many known POC diagnostic devices employ test strips or other simple detection mechanisms, and often do not amplify the target organism. Although recent advances in technology have enabled the development of “lab on a chip” devices, such devices are often not optimized for point-of-care testing. For example, some known devices and methods require continuous power usage to thermally cycle the sample, which can limit the ability to produce a portable or “in home” test. Other known devices include cumbersome resistance heaters and heat sinking arrangements that are not conducive to portable or “in home” tests. Specifically, such devices can have high power usage and can be too large to be reasonably packaged for use as a POC test.

Moreover, many known “lab on a chip” devices amplify a very small volume of sample (e.g., less than one microliter), and are therefore not suited for analyzing for multiple different indications (e.g., a 3-plex or 4-plex test).

Reducing the package size of a diagnostic device can also negatively impact the accuracy to which amplification temperatures are controlled. For example, the size, shape and packaging of certain structures (e.g., a heater, a flow member, or the like) can cause spatial variations in temperature within a reaction chamber. Moreover, tight packaging of electrical components (e.g., resistance heaters) and processors (e.g., control modules) can result in an undesirable level of electromagnetic field (EMF) noise.

Thus, a need exists for improved devices and methods for molecular diagnostic testing. In particular, a need exists for improved amplification modules, heaters and methods for amplifying a target nucleic acid in a molecular diagnostic testing device.

SUMMARY

Amplification modules and heaters for amplifying a nucleic acid within a sample are described herein. In some embodiments, an apparatus includes a substrate, a first heating element, and a second heating element. The substrate includes a first portion, a second portion, and a third portion that is between the first portion and the second portion. The first portion is characterized by a first thermal conductivity, the second portion is characterized by a second thermal conductivity, and the third portion is characterized by a third thermal conductivity. The third thermal conductivity is less than the first thermal conductivity and the second thermal conductivity. The first heating element is coupled to the first portion of the substrate, and is configured to produce a first thermal output. The second heating element is coupled to the second portion of the substrate, and configured to produce a second thermal output. The second thermal output is different from the first thermal output.

