Feasibility demonstration of a device for vitreous liquid biopsy incidental to intravitreal injection.
<h4>Purpose</h4>VitreoDx is an experimental device enabling push-button collection of a neat vitreous liquid biopsy incidental to an intravitreal injection. We explored the ability of the device to collect a sample usable for proteomic biomarker discovery and testing.<h4>Design<...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0294526&type=printable |
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| author | Alexandre R Tumlinson Jennifer M Calara Dimitri T Azar Anthony P Adamis Demetrios G Vavvas Jay M Stewart |
| author_facet | Alexandre R Tumlinson Jennifer M Calara Dimitri T Azar Anthony P Adamis Demetrios G Vavvas Jay M Stewart |
| author_sort | Alexandre R Tumlinson |
| collection | DOAJ |
| description | <h4>Purpose</h4>VitreoDx is an experimental device enabling push-button collection of a neat vitreous liquid biopsy incidental to an intravitreal injection. We explored the ability of the device to collect a sample usable for proteomic biomarker discovery and testing.<h4>Design</h4>Pilot study using ex vivo human eyes.<h4>Methods</h4>Non-vitrectomized, human eyes from nine donors 75-91 years of age were refrigerated in BSS and used within 5 days of death. Four VitreoDx devices fitted with 25G needles, and four staked needle insulin syringes with 30G needles, were inserted at equal intervals through the pars plana of each eye and held in place by a fixture. The sampling mode of each VitreoDx device was triggered to attempt to acquire a liquid biopsy up to 70 μL. The plunger of each insulin syringe was retracted to attempt to obtain a liquid biopsy with a maximum volume of 50 μL. Samples acquired with the VitreoDx were extracted to polypropylene cryovials, refrigerated to -80 ºC, and sent for offsite proteomic analysis by proximity extension assay with a focus on panels containing approved and pipelined drug targets for neovascular disease and inflammatory factors.<h4>Results</h4>Of the attempted liquid biopsies with the novel 25G VitreoDx, 92% (66 of 72) resulted in successful acquisition (>25 μL) while 89% (64 of 72) attempted by a traditional 30G needle resulted in a successful acquisition. Sample volume sufficient for proteomics array analysis was acquired by the VitreoDx for every eye. Detectable protein was found for 151 of 166 unique proteins assayed in at least 25% of eyes sampled by VitreoDx.<h4>Conclusions</h4>The high acquisition rate achieved by the prototype was similar to that achieved in previous clinical studies where a standard syringe was used with a 25G needle to biopsy vitreous fluid directly prior to standard intravitreal injection. Successful aspiration rates were likewise high for 30G needles. Together, these suggest that it is possible to routinely acquire liquid vitreous biopsies from patients who typically receive intravitreal injections with an injection device using a standard size needle without a vitreous cutter. Protein analysis shows that proteins of interest survive the sampling mechanism and may have potential to direct care in the future. |
| first_indexed | 2024-03-08T12:29:08Z |
| format | Article |
| id | doaj.art-456e7686d7884431b785d5ea1e1e33af |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-08T12:29:08Z |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-456e7686d7884431b785d5ea1e1e33af2024-01-22T05:31:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01191e029452610.1371/journal.pone.0294526Feasibility demonstration of a device for vitreous liquid biopsy incidental to intravitreal injection.Alexandre R TumlinsonJennifer M CalaraDimitri T AzarAnthony P AdamisDemetrios G VavvasJay M Stewart<h4>Purpose</h4>VitreoDx is an experimental device enabling push-button collection of a neat vitreous liquid biopsy incidental to an intravitreal injection. We explored the ability of the device to collect a sample usable for proteomic biomarker discovery and testing.<h4>Design</h4>Pilot study using ex vivo human eyes.<h4>Methods</h4>Non-vitrectomized, human eyes from nine donors 75-91 years of age were refrigerated in BSS and used within 5 days of death. Four VitreoDx devices fitted with 25G needles, and four staked needle insulin syringes with 30G needles, were inserted at equal intervals through the pars plana of each eye and held in place by a fixture. The sampling mode of each VitreoDx device was triggered to attempt to acquire a liquid biopsy up to 70 μL. The plunger of each insulin syringe was retracted to attempt to obtain a liquid biopsy with a maximum volume of 50 μL. Samples acquired with the VitreoDx were extracted to polypropylene cryovials, refrigerated to -80 ºC, and sent for offsite proteomic analysis by proximity extension assay with a focus on panels containing approved and pipelined drug targets for neovascular disease and inflammatory factors.<h4>Results</h4>Of the attempted liquid biopsies with the novel 25G VitreoDx, 92% (66 of 72) resulted in successful acquisition (>25 μL) while 89% (64 of 72) attempted by a traditional 30G needle resulted in a successful acquisition. Sample volume sufficient for proteomics array analysis was acquired by the VitreoDx for every eye. Detectable protein was found for 151 of 166 unique proteins assayed in at least 25% of eyes sampled by VitreoDx.<h4>Conclusions</h4>The high acquisition rate achieved by the prototype was similar to that achieved in previous clinical studies where a standard syringe was used with a 25G needle to biopsy vitreous fluid directly prior to standard intravitreal injection. Successful aspiration rates were likewise high for 30G needles. Together, these suggest that it is possible to routinely acquire liquid vitreous biopsies from patients who typically receive intravitreal injections with an injection device using a standard size needle without a vitreous cutter. Protein analysis shows that proteins of interest survive the sampling mechanism and may have potential to direct care in the future.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0294526&type=printable |
| spellingShingle | Alexandre R Tumlinson Jennifer M Calara Dimitri T Azar Anthony P Adamis Demetrios G Vavvas Jay M Stewart Feasibility demonstration of a device for vitreous liquid biopsy incidental to intravitreal injection. PLoS ONE |
| title | Feasibility demonstration of a device for vitreous liquid biopsy incidental to intravitreal injection. |
| title_full | Feasibility demonstration of a device for vitreous liquid biopsy incidental to intravitreal injection. |
| title_fullStr | Feasibility demonstration of a device for vitreous liquid biopsy incidental to intravitreal injection. |
| title_full_unstemmed | Feasibility demonstration of a device for vitreous liquid biopsy incidental to intravitreal injection. |
| title_short | Feasibility demonstration of a device for vitreous liquid biopsy incidental to intravitreal injection. |
| title_sort | feasibility demonstration of a device for vitreous liquid biopsy incidental to intravitreal injection |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0294526&type=printable |
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