Printed circuit board heater for an amplification module

#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.

#FIG. 1 is a perspective view schematic illustration of a thermal reaction module, according to an embodiment.

#FIG. 2 is a perspective view schematic illustration of a thermal reaction module, according to an embodiment.

#FIG. 3 is a perspective view schematic illustration of a thermal reaction module, according to an embodiment.

#In some embodiments, an apparatus is configured for a disposable, portable, single-use, inexpensive, molecular diagnostic approach. The apparatus can include one or more modules configured to perform high quality molecular diagnostic tests, including, but not limited to, sample preparation, nucleic acid amplification (e.g., via polymerase chain reaction, isothermal amplification, or the like), and detection. In some embodiments, sample preparation can be performed by isolating the target pathogen/entity and removing unwanted amplification (e.g., PCR) inhibitors. The target entity can be subsequently lysed to release target nucleic acid for amplification. A target nucleic acid in the target entity can be amplified with a polymerase undergoing temperature cycling or via an isothermal incubation to yield a greater number of copies of the target nucleic acid sequence for detection.

#In some embodiments, an amplification module includes a printed circuit board upon which a series of heaters is lithographically produced. The amplification module further includes a flow member coupled to the printed circuit board through which a sample is conveyed to amplify a target nucleic acid within the sample. The amplification can be performed, for example, by cycling the sample between various temperature set points, by maintaining the sample at a desired temperature (e.g., isothermal methods), or any other suitable method. In some embodiments, the printed circuit board also includes a processor or control module.

#In some embodiments, an amplification module includes a substrate, a first heating element, and a second heating element. The substrate defines an aperture that separates the substrate into a first portion and a second portion. 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.