Minimally Invasive early cancer detection techniques

Cancers and their staging

Cancers are characterized by an unregulated growth of cells, which ultimately spreads to other parts of the body, causing disruption of normal cellular processes, eventually leading to death. Staging of the cancer helps in classifying the cancer according to the size of the tumor. It also provides information on its spread and the extent of spread. Staging is done through methods such as TNM staging^[1], where T stands for the size of the tumor, N refers to the number of nearby lymph nodes that have cancer presence and provides information on whether or not the tumor has metastasized to other locations in the body.

Invasive vs. Non-invasive vs. Minimally invasive diagnosis

Invasive Diagnostics

Invasive cancer diagnosis includes techniques that require collection of patient samples through invasive techniques such as needle biopsy (fine needle aspiration, core needle biopsy, vacuum-assisted biopsy and image-guided biopsy), endoscopic biopsy, skin biopsy, bone-marrow biopsy or surgical biopsies. This is followed by a comprehensive evaluation of the extracted cellular/tissue sample. The evaluation is performed using techniques such as immunohistochemistry (IHC), which uses specific antibodies and stains to detect the presence of cancerous cells.

Non-Invasive diagnostics

Non-Invasive diagnostics mainly involves the use of different types of analytical instruments to detect the presence of cancerous tumors in the patient. Techniques like microarrays, surface plasmon resonance (SPR), localized SPR, vital staining, light-based detection systems and chemiluminescence. For cancers such as lung cancer, diagnosis can be performed with Magnetic Induced Tomography, Mass spectroscopy, Breath-Test, Electrochemical, Piezoelectric and Optical biosensors without the need for fixation of tissues/cells.

Apart from these there are many non-invasive optical diagnostic technologies, which can be used for cancer detection. These include Raman spectroscopy, elastic scattering spectroscopy, diffuse reflectance spectroscopy, narrow band imaging, optical coherence tomography and confocal reflectance microscopy.

Emerging companies in non-invasive cancer diagnostics

• Zetiq Technologies: Established in Israel in 1994, Zetiq Technologies is a fully-owned subsidiary of Micromedic Technologies Ltd.^[2] It uses a technology called CellDetect for morphological examination and color-based discrimination between normal and neoplastic cells. The test is characterized by high sensitivity towards low grade and early-stage tumors that are often missed by other non-invasive tests.

CellDetect has been shown to be effective at utilization as a non-invasive test for monitoring patients for Urothelial Carcinoma (UCC) recurrence, using urine as the sample. The sensitivity at UCC detection was demonstrated to be 84%. The sensitivity of detecting low-grade tumors was 78%, more than two-fold higher than that of standard urine cytology^[3]. A diagnostic value comparative study (2021) done between CellDetect, FISH (fluorescent in situ hybridization) and urine cytology for urothelial carcinoma (UC) showed superiority of CellDetect and FISH over urine cytology in UC detection. CellDetect is described as cost-effective and easy to operate than FISH.^[4]

• Exact Sciences:^[5] Established in 1995 (USA), Exact Sciences’ Cologuard^[6] can be used for non-invasive Colon cancer detection using stool-based DNA (presence of abnormal DNA sequences in the stool). Cologuard is the only non-invasive colorectal screening test that uses advanced stool DNA technology to detect the DNA and hemoglobin (red blood cells) released from abnormal cells, in case present. Cologuard can also detect some precancerous polyps that grow on the wall of the colon and may develop into cancer. In a clinical study of 10,000 participants aged 50-84 years, of average risk for colorectal cancer, Cologuard found 92% prevalence of cancers.
• Oncovision:^[7] Established in 2005 (Mexico), Oncovision’s product Mammi^[8] is a dedicated breast PET with a clinical resolution able to visualize tumors down to 2 mm, which is essential for early breast cancer detection. Its imaging process has a higher accuracy in identifying small lesions compared to traditional techniques. Since 2011, Bruker has been working with Oncovision to develop Albira PET/SPECT/CT systems. In the year 2016, the company was acquired by Bruker^[9].
• Seno medical instruments:^[10] Established in 2005 (USA), Seno medical’s product Imagio (FDA approved) uses opto-acoustics/ ultrasound for breast cancer detection. Detection of blood flow and oxygen to differentiate between benign and malignant cancers is also performed. Imagio provides better visualization of presence, absence and morphology of tumor neo-angiogenesis than mammography or CDU. Detection specificity was increased to more than 50%, with no significant loss of sensitivity. Using Imagio, clinicians have been able to identify and classify tumors as small as 3 millimeters, as well as visualize submillimeter vascular structures.^[11]
• Ascendent Diagnostics:^[12] Established in 2010 (USA) and now acquired by Namida labs^[13], their product Auria^[14] does tear-based breast cancer detection. Unlike blood, the lack of large components in tears makes small cancer markers much easier to spot. The company has expansion plans to include Pancreatic, Melanoma, Ovarian, Colon and Prostate cancers in their pipeline.
• UE LifeSciences:^[15] Established in 2009 (USA), UE Life Sciences has been working on female-focused cancer detection technologies. The company currently has two products in the market called iBreastExam and cervAIcal. iBreastExam uses Dynamic Co-Planar Capacitive Sensing (DCPC) technology to differentiate stiff breast lumps from normal breast tissue. It claims a sensitivity of 84-87% and a specificity of 80-94%. Detection of these breast lumps can assist in mammogram-based breast cancer detection^[16]. cervAIcal has been developed as a mobile colposcope with integration to the company’s iBreastExam product. A blog from NIH director Dr. Francis Collins describes cervAIcal’s AI based detection technology to be significantly more accurate than conventional Pap smears, liquid-based cytology, first-generation neural network-based cytology, and HPV testing^[17].
• Niramai:^[18] Established in 2016 (India), Niramai is one of the few Indian startups with FDA approved screening test for breast cancer. Niramai’s thermalytix^[19]-based SMILE-100 combines thermography with artificial intelligence algorithms to generate an automated interpretation report indicating breast health. Thermalytix has been described to have a positive predictive value of 66·7% in detecting benign and malignant breast lesions.

Minimally invasive diagnostics:

Minimally invasive cancer detection involves phlebotomy (puncturing and drawing blood from a vein using a cannula). These detection techniques fall under the category of liquid biopsy, which unlike tissue biopsy, uses blood component analysis to determine the person’s probability of having cancer. Liquid biopsy-based diagnostic techniques are useful in detection of cancer relapses, as unlike tissue biopsies, routine liquid biopsy tests can be performed easily to monitor the patient after treatment completion.

Table 1: Comparison of various aspects associated with the processes of liquid and tissue biopsy.^[20]

Based upon the analyte of interest, liquid biopsies can be classified as detecting Circulating Tumor Cells (CTCs), circulating tumor DNA (ctDNA), tumor associated Extracellular Vesicles (EV) or other metabolic analytes.

• CTC-based detection

Circulating Tumor Cells (CTCs) are the cancer cells that escape their original tumor site (primary site),and are in search of a new tissue/organ to invade and proliferate (metastatic or secondary tumors). These cells can be detected in the peripheral blood draws and analyzed to determine their mutation type and location of origin.

While they are available in peripheral blood, their detection poses a major challenge due to their small numbers. For a million leukocytes, only an estimated one CTC is present and hence, very sensitive techniques are employed to isolate and characterize these cells. These techniques include:

• EPISPOT: EPIthelial ImmunoSPOT assay^[21] is very sensitive in nature and can detect CTCs upto the level of single cells in the peripheral blood draws. EPISPOT has been shown to be effective at detection of CTCs from multiple types of cancerous tumors, including colon cancer, breast cancer, melanomas and prostate cancer.The assay involves binding specific antibodies to a membrane and using them to capture CTCs by adhering to specific proteins present on the surface of tumor cells. These proteins include various cell adhesion markers such as EpCAM or CD326. Once isolated, these cells can be cultured and expanded subsequently in both invitro and invivo conditions.
• CellSearch system:^[22] This technique from Menarini Silicon Biosystems employs magnetic beads, labelled with antibodies to target specific epithelial cell markers such as EpCAM. After binding to the target CTC, the magnetic beads are pulled down along with the CTCs. While they have been proven to be effective at predicting patient survival rates in cancers such as prostate cancer, not all CTCs have the EpCAM markers and the problem of cellular unviability after fixation could be seen as a major limitation to this technique.
• AdnaTest:^[23] AdnaTest kits accompany a PCR-based tumor mRNA detection system along with the EpCAM-labelled ferromagnetic beads. Companies like Qiagen offer these kits for purchase. They are effective at detecting various cancers including prostate and breast cancers.
• Microfluidic devices:^[24] CTC detection using microfluidic devices includes development of CTC-chips with patterned microgrooves. These grooves have thousands of antibody-labelled posts, which help in increasing the contact time and subsequent CTC capture.
• MIC assays: Metastasis initiating cell assay focusses on detection of invasive properties of captured CTCs. They are useful in staging cancerous tumors and detecting cancer subtypes.
• EasySep depletion^[25] and RosetteSep kits:^[26] Both of these kits from Stem Cell Technologies work towards depletion of cellular groups apart from CTCs in the sample. While EasySep uses CD45 labelled magnetic beads to separate the sample WBCs, RosetteSep uses density gradient centrifugation for the enrichment of CTCs in the sample. While they are effective, the pull down of CD45^-ve cells apart from CTCs may also happen which would make further screening necessary. A bulk WBC pull down may also lead to loss of CTCs and potentially lead to false negative results.
• Celsee systems:^[27] Celsee systems use the differences in cellular size and deformability to separate WBCs from CTCs. Microfluidic channels are employed to entrap tumor cells into the capture chambers while allowing the WBCs to pass through. These systems may overlook the smaller CTCs which might lead to false negatives.
• Apostream:^[28] Apostream harnesses the dielectric properties of the cell (polarizability) to separate out the CTCs from other cells in a process called dielectrophoresis (DEP) field-flow assist. It takes cellular characteristics such as volume, diameter, surface area, cellular density, conductivity, chromatin density and NCV ratio into account while screening.

• ctDNA-based detection
  The discovery that alterations in both the levels and sequences of major oncogenes like KRAS were present in ctDNA (circulating tumor DNA), led to their eventual discovery as a major analyte for liquid biopsy applications. These chromosomal fragments (ctDNA) have been shown to be able to travel horizontally through the apoptotic bodies and induce mutations leading to metastatic transformations in the host cells.These ctDNA fragments only account for 0.1-10% of the total circulating cell-free DNA (cfDNA), which is known to have overall levels ranging from 10-100 ng/ml. Moreover, several factors are known to increase the levels of cfDNA including exercise and inflammation, which might interfere with the detection of tumor malignancy. For effective use as tumor markers, robust parameters are required to differentiate the ctDNA from other cfDNA particles. These include the ctDNA size variations, which is found to be only 20-50 bp in length as compared to other cfDNA fragmentsthat are larger in size.ctDNA-based detection is done through two major methods:
  • Targeted approaches: Focuses on specific hotspot gene mutation and rearrangements.
  • Untargeted approaches: Focuses on broader analysis, including nucleotide and chromosomal alterations, copy number aberrations, etc.

  Targeted approaches:

  PCR based methodsinclude droplet digital PCR and BEAMing approaches

  • Droplet digital PCR^[29] uses partitioning systems to generate sample (background and target DNA) droplets, in which the target DNA amplification is done through end point PCR. The relative fractions of positive and negative droplets are counted for results. This system has shown accuracy of >75% in detecting ctDNA in samples from colorectal cancer, breast cancer and prostate cancer (localized and advanced tumors)^[30][31].
  • BEAMing^[32] (Beads, Emulsions, Amplification and Magnetics) is a modification of the traditional PCR technique, involving generation of emulsion droplet-based compartments with sample DNA, amplified using primer bound beads that are recovered magnetically or using centrifugal force.

  PARE based analysis (Personalized Analysis of Rearranged Ends)^[33]

  • Very effective for disease monitoring applications, it can be used to detect mutated ctDNA at very low concentrations (<0.001% of the plasma sample). This technique has been shown effective at detecting cancers such as colorectal and breast cancers. The technique mainly uses primers focused at flanking the breakpoint regions.^[34]

  NGS based techniques

  • Tam-seq:^[35] Tagged Amplicon deep sequencing is used to detect mutations in ctDNA from plasma samples. It is useful at detecting mutations with high sensitivities (>97%) and low allelic frequencies (2%). TAm-seq technique has been employed in identification of P53 and EGFR mutations through plasma-based analysis of patients with (OVAC) ovarian cancers. These mutations have been noted to be difficult to detect even in the solid tissue biopsies. TAm-seq has also been shown to be better at detection of early tumor responses and residual diseases than the radiographic approaches.

  Untargetted approaches:

  Shotgun massively parallel sequencing of ctDNA^[36]

  • It has been employed in detection of copy number alterations, genome profiling and mutations in breast cancer, ovarian and hepatocellular cancers.
  • Illumina MiSeq-based whole genome plasma ctDNA profiling has been used to detect chromosomal rearrangements and amplifications in castration-sensitive/resistant prostate cancer.

• Extracellular vesicle-based detection
  Extracellular vesicles (EV) are membrane-bound vesicles usually shaped like saucers, secreted by cells in different body fluids such as saliva, cerebrospinal fluid (CSF), urine and plasma. These vesicles are usually 30-100 nm in size and carry essential cargo such as RNA, DNA and protein molecules. These vesicles are important mediators of inter-cellular communications. Their role in tumor development and metastasis has made them one of the prime targets for tumor diagnosis. Isolation and analysis of these vesicles can be done through variety of established techniques:
  • Preparative ultracentrifugation (PU):^[37]
    This technique is one of the most widely used approaches for EV isolation. PU involves separation of EVs on the basis of their shape, size and particulate density. Different methods such as isopycnic, differential and moving zone ultracentrifugation is employed to prevent EV loss, improve purity and reduce contamination.^[38]
  • Ultrafiltration:
    Many kits are available in the market, which can be employed for filtration-based EV separation. These include the ExoMir kit from BioScientific, which uses syringe-based filters for EV capture from fluid like cerebrospinal fluid, serum and media^[39].
  • Size-exclusion chromatography:
    The technique involves exclusion of EVs from the stationary phase pores and earlier elution than rest of the components. This technique has been employed in T-cell suppressive EV isolation from cancers such as ovarian cancers.^[40]
  • Flow field flow fractionation^[41] and hydrostatic filtration^[42] based dialysis:
    These techniques have been employed in isolation and enrichment of EVs from neural cells and urinary microvesicles respectively.
  • ELISA:
    ELISA^[43]-based EV isolation leverages the biomarkers which are expressed or overexpressed on the vesicle surface. ELISA can be used for isolation and analysis of EVs from CSF, urine and plasma samples.
  • Magneto-immuno capture:
    This method employs magnetic particles coated with antibodies and is reported to give 10-15 times better EV yield than techniques like ultracentrifugation. Biomarkers such as CD63 tetraspanins (ThermoFisher) are used for enrichment purposes in these techniques.
  • Precipitation based techniques:
    Kits such as ExoQuick PLUS from System Biosciences use polymer-based isolation of EVs from fluids such as serum and plasma with shorter time periods and lesser contaminants.^[44]
  • Microfluidics-based enrichment:^[45]
    Microfluidic techniques like ExoChip have been shown to be effective at EV isolation from serum of pancreatic cancer patients. Some of these techniques include microscale ciliated pillars which work towards capture of extracellular vesicles and filtering out proteins and other cellular debris.

Though the use of Extracellular Vesicles (EVs) in tumor detection has gained rapid advances, there are multiple challenges that need to be addressed. These include yields of cargo from the exosomes, heterogeneity of EVs, protocol standardization, sample pre-treatment and efficiency of isolation.

• Other emerging analytes for liquid biopsy

• Tumor-educated platelets (TEP) are emerging as novel biomarkers, as RNA sequencing analysis of TEP-RNA was recently reported to accurately predict both early and late – Non-Small Cell Lung Carcinoma with more than 80% accuracy.[xxvi]
• Some metabolites such as BCAA (Branched Chain Amino Acids) have been shown to be present at increased concentrations in pancreatic carcinoma, while the same are seen to be heavily reduced in the case of Non-Small Cell Lung Carcinoma. The alterations in the levels of these metabolites could be potentially used as markers for early cancer detection.^[47]
• Studies are increasingly focusing on miRNA signatures for use as diagnostic tools in cancer detection.
• Some studies have established the cfDNA (cell free DNA) level decrease accompanied by an increase in fragment size as positive signs of therapeutic drug response, while the opposite has been shown to be occurring in the case of tumor recurrence.^[48]

Emerging companies working on minimally invasive diagnostics

• Datar cancer genetics:^[49] Established in 1992 (India), the company’s Trublood™ test is a minimally invasive test for the detection of CTC in blood samples. Trublood^[50] claims >99% accuracy (sample size: 40,000+) with capabilities to detect very early stage (stage 0- in-situ cancer) as well as stage 1 and 2 cancers.
• Cytognos:^[51] Established in 1996 (Spain), Cytognos’ EuroFlow™^[52] (Next Generation Flow™) claims an orientation efficiency of 98.3% for non-ambiguous lineage cases targeting the detection of CTPC (Circulating Tumor Plasma Cells) in multiple myeloma and Acute Lymphoblastic Leukemia MRD (Minimal Residual Disease). The company has been Acquired by Becton, Dickinson and Company.
• Clinical genomics technologies:;^[53] Established in 2006 (Australia), Clinical genomics’ product Colvera^[54] is a biomarker-based test to detect the presence of Methylated BCAT and IKZF1 biomarkers in blood. The company claims detection of all the 4 cancer stages with a specificity of 98%. Colvera has been shown to be able to detect 3 times more colorectal cancer patients compared to CEA.
• LungLife AI:^[55] Established in 2006 (USA), the company uses the LungLB^[56] test for FISH (Fluorescence In-Situ Hybridization) based CTC detection from blood. The test has been shown to distinguish between the benign and malignant tumors in lung nodules. It is claimed to have a sensitivity of 81% and specificity of 87% (threshold 2.17 CTC/10,000 cells analyzed). The company is funded by the Livzon pharmaceutical group.
• Provista Diagnostics:^[57] Established in 2007 (USA), Provista uses the TBIA^[58] product for AI-based cancer detection. TBIA detects the immune system’s response to the presence of tumor through blood-based FTIR -biochemical signature analysis of immune cells. This is done through analysis of lipids, proteins, carbohydrates and nucleic acids.

The company is also on the way to launch a blood-based breast cancer detection test called Videssa^[59] in 2023. Videssa will use protein biomarkers in the blood to detect the presence of Tumor Associated Autoantibodies (TAAbs). Videssa has been described as being able to rule out cancer for BIRADS 3 & 4 with high accuracy irrespective of tissue density.

• Biolidics:^[60] Established in 2009 (Singapore), Biolidics uses a patented CTC enrichment platform (ClearCell® FX1 System) for lung and breast cancer detection, using microfluidics technology (CTChip®FR1 biochip). The company has a presence in many countries including Singapore, China, Hong Kong, Japan, US and EU. The main limitation of the detection system includes difficulty in capturing smaller cancer cells like colon cancers and small cell lung cancers. The technology has been proven to be useful in enrichment of large CTCs such as melanoma and breast CTCs. The technology has been able to detect CTC in 88% of samples from melanoma patients. The incorporation of a DNA biomarker along with mRNA profiling has increased the overall CTC detection capability by over 57%.
• Cleveland diagnostics:^[61] Established in 2013 (USA), the company uses the IsoPSA prostate cancer test^[62] to measure total amount of PSA protein circulating in the blood. Alpha blockers and 5α-reductase inhibitors (prescribed for benign prostate hyperplasia (BPH)) do not interfere with the results of the IsoPSA test. The test showed a sensitivity of 93% in Oct. 2021 (and the problems are being addressed as evident of a report published in June 2022.) The company is currently collaborating with Cleveland Clinic.
• Bluestar Genomics:^[63] Established in 2016 (USA) and rebranded as Clearnote Health, the company uses biomarker 5-hydroxymethylcytosine (5hmC) for differentiating between normal and cancerous tissues. The test can also distinguish between the different locations of cancer. The epigenomics-based approach combined with machine learning aids in early detection of cancer as compared to the established methods. This method sharply focuses on 1% of the genome, in which the changes correspond to healthy cells getting transformed to cancer cells. Among a pilot study with 48 breast, 55 lung, 32 prostate and 53 pancreatic cancer subjects, along with a control cohort of 180 subjects (non-cancer), 5hmC test found the probability of cancer as 0.89, 0.84, 0.95 and 0.83 respectively for breast, lung, pancreatic and prostate cancer.

The company started a clinical trial in December 2022 for its proprietary epigenomic method for pancreatic cancer detection (focused on the high-risk group of type II Diabetes patients).

• GRAIL:^[64] Founded in 2016 and acquired by Illumina, GRAIL’s Galleri test^[65] is the first clinically validated MCED (Multi-Cancer Early Detection) test to detect over 50 types of cancers with a specificity of 99.5%. Galleri can predict the cancer’s tissue type and its origin with an accuracy of 88%. The test checks for cell-free DNA and identifies whether it comes from healthy or cancer cells. Galleri can check for specific methylation patterns that might reveal a cancer cell’s signature. Galleri test is FDA-approved. GRAIL’s laboratory has been CLIA-approved and CAP- accredited. GRAIL recently announced a strategic partnership with HCA healthcare’s Sarah Cannon Cancer Institute for the MCED test, which will be made available to eligible patients through HCA Healthcare physicians. HCA Healthcare is actively involved in the multi-center interventional study, PATHFINDER 2.^[66]
• Guardant Health:^[67] Founded in 2012 (USA), Guardant health is a precision oncology company that uses blood tests, data sets, and analytics for diagnostics and treatment of cancer patients. It currently has two products on the market for early cancer detection and one for patients with advanced cancer. The early cancer tests include products like SHIELD^[68] and Guardant Reveal^[69]. Reveal test is designed to detect circulating tumor DNA (ctDNA) for assessment of Minimal Residual Disease (MRD) in early-stage lung, colorectal and breast cancers. The SHIELD test is claimed to be helpful for blood based (ctDNA) detection of colorectal cancer. This test is under study for extension into lung cancers as well. Guardian Health’s recent patent application US20230313315A1^[70] claims a method of enriching cell-free DNA from a patient’s sample for variety of genes including both oncogenes (ex. EGFR) and tumor suppressors (ex. TP53) for its sequencing-based detection.
• SeekIn Inc:^[71] Founded in 2018, the company has five products, including SeekInCare, SeekInCure, SeekInClarity, OncoSeek and LeukoPrint. OncoSeek is a Multi-cancer Early Detection test for adults and is a part of recent additional validation studies by Seekin Inc. to evaluate OncoSeek’s^[72] ability to detect up to nine cancer types along with tissue of origin prediction using only a tube of blood. OncoSeek was earlier evaluated in China and US through 3 cohorts of 9,382 participants. This time two new cohorts have been added and combined resultsback OncoSeek’s sensitivity at 52% along with a specificity of 93%. This shows a significant reduction in the false positive rate of 7% from 46% corresponding to the conventional clinical methods.

• AOA Dx:^[73] Established in 2020 (USA), AOA’s products (AKRIVIS GD^[74] and GlycoLocate^[75]) use GD2 and GD3-based tumor biomarkers for liquid biopsy-based detection of ovarian cancer. GlycoLocate platform can differentiate between cancers down to their tissue of origin in both symptomatic and non-symptomatic patients. AOA has started a clinical trial for its test platform (OVERT clinical trial) and the preliminary reports show high specificity and sensitivity across both postmenopausal and premenopausal women.

• X-zell:^[76] Established in 2014 (Singapore), X-zell’s digital single-cell analytics technology has been shown to be an important asset in cytopathology. X-zell has many products aimed at improving cytology processes such as Cryofixator, Cryostainer, hybrid microscopy (combining brightfield with immunofluorescence microscopy) and hMX cell separation. These techniques have been employed at detection of diseases including cancers. X-zell has been collaborating with Singapore General Hospital and National University Hospital at Singapore for early detection of clinically significant prostate cancer in whole blood. X-zell’s pilot studies have also shown that its products as an additional diagnostic tool might help in about 70% reduction in unnecessary biopsies.

Reference:

1. Cancer staging
2. Zetiq technologies
3. Color based cellular discrimination
4. CellDetect diagnostic value comparison
5. Exact sciences
6. Cologuard
7. Oncovision
8. Mammi
9. Oncovision acquisition
10. Seno Medical
11. Imagio
12. Ascendant Dx
13. Namida labs
14. Auria
15. UE Lifesciences
16. ibreastexam
17. cervAIcal
18. Niramai
19. Niramai Thermalytix
20. Liquid vs. tissue biopsy
21. EPISPOT
22. Cellsearch
23. Adna Test
24. Microfluidic CTC detection
25. EasySep kit
26. RossetteSep kit
27. Celsee systems
28. Apostream
29. Droplet digital PCR
30. ddPCR
31. ddPCR
32. BEAMing
33. PARE
34. PARE
35. Tam-seq
36. Shotgun sequencing
37. Exosome shuttling
38. Exosome Isolation
39. Exomir
40. Size exclusion chromatography
41. Flow field flow fractionation
42. hydrostatic filtration
43. ELISA
44. ExoQuick PLUS
45. Microfluidics based enrichment
46. Tumor educated platelets
47. BCAA based detection
48. cfDNA
49. Datar cancer genetics
50. Trueblood
51. Cytognos
52. Euroflow
53. Clinical genomics technologies
54. Colvera
55. LunglifeAI
56. LungLB test
57. Provista Dx
58. TBIA
59. Videssa
60. Biolidics
61. Cleveland Dx
62. IsoPSA test
63. Bluestar genomics
64. GRAIL
65. Galleri test
66. GRAIL and HCA healthcare partnership
67. Guardant health
68. Shield
69. Guardant reveal
70. US20230313315A1
71. Seekin Inc.
72. Oncoseek
73. AOA Dx
74. Akrivis GD
75. Glycolocate
76. X-zell

Posted Date: January, 2024