Liquid biopsies are gaining popularity as a less invasive alternative to tissue biopsies that have been the mainstay of cancer diagnostics to date. Recently, the quantification of mutations in circulating tumor DNA (ctDNA) by next-generation sequencing (NGS) has been gaining popularity. Targeted NGS approaches are preferable in ctDNA analysis as they provide greater sequencing depth and affordability compared to whole genome NGS. Targeted NGS can be achieved through various library preparation methods, each with distinct advantages and limitations. Here we introduce Bridge Capture, a novel technology that combines the advantages of market-leading liquid biopsy technologies while eliminating the need to compromise between scalability, cost-efficiency, sensitivity, or panel size. We compared Bridge Capture to leading commercial technologies currently available in cancer diagnostics; ArcherTM LIQUIDPlexTM and AmpliSeqTM Cancer HotSpot Panel v2 for Illumina. We found high mutant allele frequency (MAF) concordance as well as the lowest MAF among the three technologies on matched contrived colorectal biospecimens mimicking ctDNA. We showed the reproducibility of Bridge Capture by observing a high correlation between results from two independent laboratories. Additionally, we demonstrate the capability of Bridge Capture to affordably utilize bench-top sequencers for low MAF patient samples. Therefore, we believe that Bridge Capture will considerably enhance cancer diagnostics as a cost efficient, simple, rapid and sensitive precision diagnostic tool.

Conflict of Interest Statement As the Chief Technology Officer (CTO) of Genomill Health Inc, I acknowledge the potential conflicts of interest in relation to the submitted manuscript titled "Bridge Capture Permits Cost-Efficient, Rapid and Sensitive Molecular Precision Diagnostics" Specifically: Equity Holdings: I hold equity in Genonmill, and this financial interest may be seen as influencing the research outcomes. The same applies to JL and JB who also hold equity in the company. Stock Options: In addition to direct equity, the rest of the authors are entitled to stock options in Genomill. This arrangement could be perceived as a potential incentive to influence the study's results in a favorable direction for the company. Employment: In addition to direct equity and stock options, the authors SA, AK, TH, AM, TR, NL and JPP are currently employed at Genomill. Patent Rights: The research detailed in this manuscript is related to Genomill patents EP-3673081, JP-7074978, EP-4060049, US-11486003 and EP-4060050. Genomill is in the process of filing patents related to this work, and MT, TH, JPP and AK are named inventors on these patent applications. The potential for financial gain from these patents may be viewed as a conflict of interest. Others: JB has received honoraria from Novo Nordisk and Boehringer Ingelheim. In preparing this manuscript, we have made every effort to ensure that the research is conducted and presented objectively. The data, analyses, and conclusions herein are the result of rigorous scientific inquiry and are not influenced by our financial interests. The study's design, data collection, analysis, interpretation, and the writing of the manuscript were conducted independently of Genomill's commercial interests. We disclose these potential conflicts in the spirit of transparency and to aid the peer review process. We affirm that the information provided here is accurate and complete to the best of our knowledge.

This study was funded by venture capital from Voima Ventures (https://voimaventures.com/), Avohoidon Tutkimussaatio (https://www.avohoidontutkimussaatio.fi/en/home/) and Almaral (https://almaral.eu/).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Research Ethics Committee of The wellbeing services county of Southwest Finland waived ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors.