Nanofiber capsules for minimally invasive sampling of biological specimens from gastrointestinal tract

Abstract

Accurate and rapid point-of-care tissue and microbiome sampling is critical for early detection of cancers and infectious diseases and often result in effective early intervention and prevention of disease spread. In particular, the low prevalence of Barrett's and gastric premalignancy in the Western world makes population-based endoscopic screening unfeasible and cost-ineffective. Herein, we report a method that may be useful for prescreening the general population in a minimally invasive way using a swallowable, re-expandable, ultra-absorbable, and retrievable nanofiber cuboid and sphere produced by electrospinning, gas-foaming, coating, and crosslinking. The water absorption capacity of the cuboid- and sphere-shaped nanofiber objects is shown ∼6000% and ∼2000% of their dry mass. In contrast, unexpanded semicircular and square nanofiber membranes showed <500% of their dry mass. Moreover, the swallowable sphere and cuboid were able to collect and release more bacteria, viruses, and cells/tissues from solutions as compared with unexpanded scaffolds. In addition to that, an expanded sphere shows higher cell collection capacity from the esophagus inner wall as compared with the unexpanded nanofiber membrane. Taken together, the nanofiber capsules developed in this study could provide a minimally invasive method of collecting biological samples from the duodenal, gastric, esophagus, and oropharyngeal sites, potentially leading to timely and accurate diagnosis of many diseases. STATEMENT OF SIGNIFICANCE: Recently, minimally invasive technologies have gained much attention in tissue engineering and disease diagnosis. In this study, we engineered a swallowable and retrievable electrospun nanofiber capsule serving as collection device to collect specimens from internal organs in a minimally invasive manner. The sample collection device could be an alternative endoscopy to collect the samples from internal organs like jejunum, stomach, esophagus, and oropharynx without any sedation. The newly engineered nanofiber capsule could be used to collect, bacteria, virus, fluids, and cells from the abovementioned internal organs. In addition, the biocompatible and biodegradable nanofiber capsule on a string could exhibit a great sample collection capacity for the primary screening of Barret Esophagus, acid reflux, SARS-COVID-19, Helicobacter pylori, and gastric cancer.

Keywords: Barret esophagus; Gastrointestinal tract; Nanofiber capsule; SARS-CoV-2; Sample collection.

Fig. 1.

Swallowable, re-expandable, ultra-absorbable, and retrievable nanofiber capsules for biological specimen collection. a-b) Schematic illustration of the nanofiber capsule on a string in stomach, dissolution of the capsule at gastric site, and re-expansion and retrieval of the nanofiber object. c) The possible sample collection sites like duodenal, gastric, esophagus and oropharyngeal sites.

Fig. 2.. Fabrication of swallowable, re-expandable, ultra-absorbable, and retrievable nanofiber capsules.

a, b) Schematic illustration of the fabrication of cuboid-shaped nanofiber objects expanded from a 2D nanofiber mat. c-e) Photographs and SEM images of a cuboid-shaped nanofiber object. f, g) Schematic illustration of the fabrication of a sphere-shaped nanofiber object transformed from a 2D nanofiber mat. h-j) Photographs and SEM images of a sphere-shaped nanofiber object. k) Photograph shows a nanofiber sphere attached with a string. The small red square in (i) represents the thermally welded region. l) A dissolvable gelatin capsule encapsulated with a compressed nanofiber sphere on a string. The white arrows indicate the attached string. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3.. The dissolution time of gelatin capsules encased with different nanofiber objects at different pHs (n = 3).

Cuboid: capsules encased with cuboid-shaped nanofiber objects, Sphere: capsules encased with sphere-shaped nanofiber objects, Unexpanded square: capsules encased with unexpanded square nanofiber membranes, and Unexpanded semicircle: capsules encased with unexpanded semicircular nanofiber membranes.

Fig. 4.. Bacteria collection.

a) Photographs of the plates of MRSA colonies after recovery from cuboid- and sphere-shaped nanofiber objects and semicircular and square nanofiber membranes which were used for swabbing stock solutions of 10⁶ , 10⁵ , 10⁴ and 10³ CFU/ml. b-e) MRSA colony counts after recovery from cuboid- and sphere-shaped nanofiber objects and semicircular and square nanofiber membranes which were used for swabbing stock solutions of 10⁶ , 10⁵ , 10⁴ and 10³ CFU/ml.

Fig. 5.. SARS-Cov-2 detection and identification.

a) Schematic representation from SARS-CoV-2 detection using PCR and swabbing. b) Cycle threshold values at each SARS-CoV-2 titer following swabbing. c) Converted SARS-CoV-2 concentration in pfu/ml. *p<0.05, **p<0.01, ***p<0.001.

Fig. 6.. Tissue collection from swine esophagus.

a) Photographs showing the cell/tissue collection process from swine esophagus using sphere-shaped nanofiber objects. b) Photographs showing the cell/tissue collection process from swine esophagus using semicircular nanofiber membranes. c) Photograph showing the inside view of the swine esophagus. The yellow dotted line indicates the inner wall of swine esophagus. d) Photograph showing the nanofiber sphere in the swine esophagus. White arrows indicate the nanofiber sphere and the attached string, respectively. e, f) Representative H&E stained images of collected tissues from the swine esophagus. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)