New and Improved: The Latest Research in Disease Screening

When most people think of disease screening, they envision a range of common blood tests, scans, and simple procedures like colonoscopies or cervical smears. But research is unveiling a wealth of new screening options for conditions from allergies to kidney stones—and expanding the role of the lab in detecting these diseases.

Promising platforms

Experimental testing devices are promising faster and more effective detection across a variety of cancers. A new lab-on-a-chip technique that uses gold nanoparticle films to isolate cancer exosomes for spectroscopic analysis has been found to detect evidence of lung cancer 10 times faster—and 14 times more sensitively—than existing methods for exosome liquid biopsy.¹ By using nanoparticles with a twisted disk shape, the study authors were able to capture exosomes from blood plasma for analysis via circular dichroism spectroscopy, which can detect microscopic changes in exosome shape that signal cancer- or treatment resistance-related protein mutations. The technique’s extreme sensitivity arises from the fact that the nanoparticles are oriented uniformly on the microfluidic chip used for analysis, strengthening the spectroscopic signal.

Devices like these may speed up disease diagnosis—but access remains an issue for many patients. For this reason, a group of Texas researchers has developed a portable immunoassay device that costs only a few dollars, processes samples in an hour or less, and requires no specialized instruments.² The lab-on-a-chip uses a method known as “paper-in-polymer-pond,” in which patient samples applied to prepared chromatography paper flow through a layer of polymer into microwells, eliminating the need for time-consuming pipetting or costly automation. The results can be quantified using a device as simple as a smartphone or digital camera. In sensitivity tests, the chip was able to detect carcinoembryonic and prostate-specific antigens at approximately 10-fold lower concentrations than conventional ELISA testing, offering promise for the future of biomarker-based screening in resource-limited settings.

New testing methods are expanding options for allergy screening as well. At the moment, many people are not diagnosed with allergies until their first reaction, which can be disastrous for those with severe reactions. Even following this, the gold standard for diagnosis is a supervised challenge in which the patient is exposed to the allergen to induce a reaction. In search of a better way, Swiss and Canadian researchers have developed a cell-based assay that uses patient serum to mimic an in vitro allergic reaction.³ If present in the serum, IgE antibodies—which mediate allergic responses—bind to the mast cells, sensitizing them to the allergen in question. The mast cells are then stimulated with the allergen and the proportion of activated mast cells measured. When tested on 80 patients with peanut allergies and 32 without, the test demonstrated 93 percent sensitivity and 96 percent specificity. Currently, it requires more time and labor than appropriate for population screening, but the gains in accuracy and patient comfort may improve screening options for patients at risk or suspected of having severe allergies.

Boosting biomarkers

Even without the assistance of microfluidic chips, new biomarkers are breaking ground in screening situations. Alzheimer’s disease is one example. Although definitive diagnosis can be tricky, especially in the early stages of the disease, researchers are working to develop biomarkers that can screen for not only Alzheimer’s itself, but also related pathological processes. By measuring the plasma levels of 116 proteins in a cohort of 113 patients aged 65 or older, all of whom had no or very mild cognitive impairment, a group from the University of Pittsburgh identified potential biomarkers associated with neuroinflammation, synaptic dysfunction, or vascular dysfunction in preclinical Alzheimer’s disease.⁴ Because these markers are easily evaluated via blood draw and show changes even in asymptomatic patients, they could potentially be used not only in the diagnosis and monitoring of Alzheimer’s disease, but also to screen for the condition in at-risk populations.

Another research group took aim at pancreatic ductal adenocarcinoma, whose survival rate essentially triples when diagnosed early.⁵ Unfortunately, viable screening options are limited; most patients require imaging for diagnosis and the most commonly used biomarker—CA19-9—has low sensitivity and specificity for the disease. Together, these factors mean that patients are rarely diagnosed until their condition has progressed. To improve detection, researchers combined several previously reported pancreatic cancer biomarkers into a set of panel tests with higher sensitivity and specificity than any single analyte.⁶ The result: panels that not only improved disease detection in the context of confounding factors like other cancers or pancreatitis, but also captured patients who were missed using CA19-9 alone. The authors anticipate that, in the future, individual biomarkers may have further applications in treatment selection; the tumor-specific mucin MUC5AC, for instance, outperformed CA19-9 in distinguishing between resectable and nonresectable tumors.

Prenatal biomarkers are another area of interest, with blood, urine, and amniotic fluid samples often used to predict the risk of pregnancy complications or fetal abnormalities. For disorders like chromosomal abnormalities or neural tube defects, maternal blood testing is common—but other conditions have fewer options. Single-ventricle heart defects, considered among the most critical of congenital heart defects,⁷ are diagnosed via complex ultrasonography and fetal echocardiography, which can be expensive or difficult for prospective parents to access. Now, however, new research suggests that profiling cell-free microRNA in maternal blood can reveal changes—such as upregulations in microRNAs that suppress cardiomyocyte proliferation—that signpost these defects, allowing advance planning for the immediate cardiac care these infants need at birth.⁸

Beyond blood

Despite affecting as many as one in 10 women and girls of reproductive age, endometriosis remains difficult to diagnose. Patients who lack access to costly imaging and exploratory surgery may spend years seeking explanations for their pain and other symptoms. To alleviate this burden, scientists at Baylor College of Medicine compared the stool microbiomes and metabolomes of people with and without endometriosis, seeking differences that could be used for screening or diagnostic purposes.⁹ They discovered that levels of a specific bacteria-derived metabolite, 4-hydroxyindole, were lower in people with endometriosis, and that this metabolite suppressed the onset and progression of endometriosis in mouse and preclinical models of the disease. Because stool testing is noninvasive and many facilities already have the necessary equipment and training, 4-hydroxyindole could offer a promising route to endometriosis screening in a wide range of settings.

Like stool, urine is easily obtained and analyzed, making it a valuable biofluid for screening—especially in the case of genitourinary tract issues, whose diagnosis often necessitates a combination of clinical examinations, lab tests, and imaging. New research suggests that changes to the urine metabolome and transcriptome—which are enriched for genitourinary RNAs and metabolic signals relative to plasma—can signal the presence of conditions from kidney stones to cancer.¹⁰ The study authors particularly emphasized the elevation of prostate cell type-specific signals in urine cell-free RNA. The elevation of these signals is important due to the need for more reliable biomarkers for prostate cancer screening. More research is needed to evaluate the new technique’s promise in the clinic, but the authors are optimistic about its potential to improve screening for a variety of genitourinary diseases.

Effective screening and early diagnosis can be game changers for both patients and healthcare systems by facilitating better outcomes, less invasive treatment options, and lower cost burdens for healthcare systems. To this end, researchers are continually seeking new techniques, technologies, and biomarkers to improve the ease and reliability of screening. However, with equitable access a cornerstone of effective screening programs, it’s vital to ensure that this enthusiasm for new ideas comes alongside opportunities for people to learn about and engage with available screening options. Such opportunities will help ensure that these tests live up to their promise of improved healthcare for all.

References:

1. 1. Kang Y-T et al. Chiroptical detection and mutation analysis of cancer-associated extracellular vesicles using microfluidics with oriented chiral nanoparticles. Matter. 2024; online ahead of print. doi:10.1016/j.matt.2024.09.005.
   2. Timilsina SS, Li X. A paper-in-polymer-pond (PiPP) hybrid microfluidic microplate for multiplexed ultrasensitive detection of cancer biomarkers. Lab Chip. 2024;24(21):4962–4973. doi:10.1039/d4lc00485j.
   3. Bachmeier-Zbären N et al. Clinical utility analysis of the Hoxb8 mast cell activation test for the diagnosis of peanut allergy. Allergy. 2024; online ahead of print. doi:10.1111/all.16341.
   4. Zeng X et al. Multi-analyte proteomic analysis identifies blood-based neuroinflammation, cerebrovascular and synaptic biomarkers in preclinical Alzheimer’s disease. Mol Neurodegener. 2024;19(1):68. doi:10.1186/s13024-024-00753-5.
   5. American Cancer Society. Cancer Facts & Figures 2024. January 17, 2024. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2024/2024-cancer-facts-and-figures-acs.pdf.
   6. Haab B et al. A rigorous multi-laboratory study of known PDAC biomarkers identifies increased sensitivity and specificity over CA19-9 alone. Cancer Lett. 2024;604:217245. doi:10.1016/j.canlet.2024.217245.
   7. Oster ME et al. Temporal trends in survival among infants with critical congenital heart defects. Pediatrics. 2013;131(5):e1502–e1508. doi:10.1542/peds.2012-3435.
   8. Alonzo M et al. Cell-free RNA signatures in maternal blood with fetal congenital heart disease. Circ Res. 2024;135(10):1021–1024. doi:10.1161/CIRCRESAHA.124.325024.
   9. Talwar C et al. Identification of distinct stool metabolites in women with endometriosis for non-invasive diagnosis and potential for microbiota-based therapies. Med. 2024;S2666-6340(24)00373-8. doi:10.1016/j.medj.2024.09.006.
   10. Vorperian SK et al. Deconvolution of human urine across the transcriptome and metabolome. Clin Chem. 2024;70(11):1344–1354. doi:10.1093/clinchem/hvae137.