diff --git a/bids-validator-web/package.json b/bids-validator-web/package.json
index 3f77e0643..75dd8310d 100644
--- a/bids-validator-web/package.json
+++ b/bids-validator-web/package.json
@@ -5,6 +5,7 @@
   "main": "index.js",
   "license": "MIT",
   "dependencies": {
+    "@babel/runtime": "^7.16.7",
     "bootstrap": "^4.3.0",
     "bowser": "^1.0.0",
     "next": "^11.1.2",
diff --git a/bids-validator/bids_validator/rules/file_level_rules.json b/bids-validator/bids_validator/rules/file_level_rules.json
index 54fb504f7..0c36e5081 100644
--- a/bids-validator/bids_validator/rules/file_level_rules.json
+++ b/bids-validator/bids_validator/rules/file_level_rules.json
@@ -523,5 +523,70 @@
     "tokens": {
       "@@@_pet_ext_@@@": ["blood\\.tsv\\.gz", "blood\\.tsv", "blood\\.json"]
     }
+  },
+
+  "microscopy": {
+    "regexp": "^[\\/\\\\](sub-[a-zA-Z0-9]+)[\\/\\\\](?:(ses-[a-zA-Z0-9]+)[\\/\\\\])?micr[\\/\\\\](sub-[a-zA-Z0-9]+)(?:(_ses-[a-zA-Z0-9]+))?(?:_sample-[a-zA-Z0-9]+)(?:_acq-[a-zA-Z0-9]+)?(?:_stain-[a-zA-Z0-9]+)?(?:_run-[0-9]+)?(?:_chunk-[0-9]+)?((@@@_microscopy_type_@@@)(@@@_microscopy_ext_@@@))$",
+    "tokens": {
+      "@@@_microscopy_type_@@@": [
+        "_TEM",
+        "_SEM",
+        "_uCT",
+        "_BF",
+        "_DF",
+        "_PC",
+        "_DIC",
+        "_FLUO",
+        "_CONF",
+        "_PLI",
+        "_CARS",
+        "_2PE",
+        "_MPE",
+        "_SR",
+        "_NLO",
+        "_OCT",
+        "_SPIM"
+      ],
+      "@@@_microscopy_ext_@@@": [
+        ".ome\\.tif",
+        ".ome\\.btf",
+        ".tif",
+        ".png"
+      ]
+    }
+  },
+  "microscopy_photo": {
+    "regexp": "^[\\/\\\\](sub-[a-zA-Z0-9]+)[\\/\\\\](?:(ses-[a-zA-Z0-9]+)[\\/\\\\])?micr[\\/\\\\](sub-[a-zA-Z0-9]+)(?:(_ses-[a-zA-Z0-9]+))?(?:_sample-[a-zA-Z0-9]+)(?:_acq-[a-zA-Z0-9]+)?(@@@_photo_ext_@@@)$",
+    "tokens":{
+      "@@@_photo_ext_@@@": [
+        "_photo\\.jpg",
+        "_photo\\.png",
+        "_photo\\.tif"
+      ]
+    }
+  },
+  "microscopy_json": {
+    "regexp": "^[\\/\\\\](sub-[a-zA-Z0-9]+)[\\/\\\\](?:(ses-[a-zA-Z0-9]+)[\\/\\\\])?micr[\\/\\\\](sub-[a-zA-Z0-9]+)(?:(_ses-[a-zA-Z0-9]+))?(?:_sample-[a-zA-Z0-9]+)?(?:_acq-[a-zA-Z0-9]+)?(?:_stain-[a-zA-Z0-9]+)?(?:_run-[0-9]+)?(?:_chunk-[0-9]+)?(@@@_microscopy_type_@@@)\\.json$",
+    "tokens": {
+      "@@@_microscopy_type_@@@": [
+        "_TEM",
+        "_SEM",
+        "_uCT",
+        "_BF",
+        "_DF",
+        "_PC",
+        "_DIC",
+        "_FLUO",
+        "_CONF",
+        "_PLI",
+        "_CARS",
+        "_2PE",
+        "_MPE",
+        "_SR",
+        "_NLO",
+        "_OCT",
+        "_SPIM"
+      ]
+    }
   }
 }
diff --git a/bids-validator/bids_validator/rules/session_level_rules.json b/bids-validator/bids_validator/rules/session_level_rules.json
index 48fd6c724..241ef3c10 100644
--- a/bids-validator/bids_validator/rules/session_level_rules.json
+++ b/bids-validator/bids_validator/rules/session_level_rules.json
@@ -201,5 +201,30 @@
         "UNCInfant2V23"
       ]
     }
+  },
+
+  "microscopy_ses": {
+    "regexp": "^[\\/\\\\](sub-[a-zA-Z0-9]+)[\\/\\\\](?:(ses-[a-zA-Z0-9]+)[\\/\\\\])?\\1(_\\2)?(?:_sample-[a-zA-Z0-9]+)?(?:_acq-[a-zA-Z0-9]+)?(?:_stain-[a-zA-Z0-9]+)?(?:_run-[0-9]+_)?(?:_chunk-[0-9]+)?(@@@_microscopy_ses_type_@@@)$",
+    "tokens": {
+      "@@@_microscopy_ses_type_@@@": [
+        "_TEM.json",
+        "_SEM.json",
+        "_uCT.json",
+        "_BF.json",
+        "_DF.json",
+        "_PC.json",
+        "_DIC.json",
+        "_FLUO.json",
+        "_CONF.json",
+        "_PLI.json",
+        "_CARS.json",
+        "_2PE.json",
+        "_MPE.json",
+        "_SR.json",
+        "_NLO.json",
+        "_OCT.json",
+        "_SPIM.json"
+      ]
+    }
   }
 }
diff --git a/bids-validator/bids_validator/rules/top_level_rules.json b/bids-validator/bids_validator/rules/top_level_rules.json
index 9757f6e53..8849157b6 100644
--- a/bids-validator/bids_validator/rules/top_level_rules.json
+++ b/bids-validator/bids_validator/rules/top_level_rules.json
@@ -15,7 +15,9 @@
         "phase2.json",
         "fieldmap.json",
         "events.json",
-        "scans.json"
+        "scans.json",
+        "samples.json",
+        "samples.tsv"
       ]
     }
   },
@@ -133,5 +135,30 @@
     "tokens": {
       "@@@_other_top_files_ext_@@@": ["physio\\.json", "stim\\.json"]
     }
+  },
+
+  "microscopy_top": {
+    "regexp": "^[\\/\\\\](?:ses-[a-zA-Z0-9]+_)?(?:_sample-[a-zA-Z0-9]+)?(?:_acq-[a-zA-Z0-9]+)?(?:_stain-[a-zA-Z0-9]+)?(?:_run-[0-9]+)?(?:_chunk-[0-9]+)?(?:@@@_microscopy_top_ext_@@@)$",
+    "tokens": {
+      "@@@_microscopy_top_ext_@@@": [
+        "_TEM\\.json",
+        "_SEM\\.json",
+        "_uCT\\.json",
+        "_BF\\.json",
+        "_DF\\.json",
+        "_PC\\.json",
+        "_DIC\\.json",
+        "_FLUO\\.json",
+        "_CONF\\.json",
+        "_PLI\\.json",
+        "_CARS\\.json",
+        "_2PE\\.json",
+        "_MPE\\.json",
+        "_SR\\.json",
+        "_NLO\\.json",
+        "_OCT\\.json",
+        "_SPIM\\.json"
+      ]
+    }
   }
 }
diff --git a/bids-validator/bin/bids-validator b/bids-validator/bin/bids-validator
index 65840cd95..e5221accf 100755
--- a/bids-validator/bin/bids-validator
+++ b/bids-validator/bin/bids-validator
@@ -8,6 +8,7 @@ function entry(cli) {
 try {
   // Test if there's a development tree to run
   require.resolve('../cli.js')
+  process.env.ESBUILD_MAX_BUFFER = 64 * 1024 * 1024
   // For dev, use esbuild-runner
   require('esbuild-runner/register')
   const { default: cli } = require('../cli.js')
diff --git a/bids-validator/package.json b/bids-validator/package.json
index a01350336..054da6d47 100644
--- a/bids-validator/package.json
+++ b/bids-validator/package.json
@@ -58,7 +58,9 @@
     "stream-browserify": "^3.0.0",
     "table": "^5.2.3",
     "yaml": "^1.10.2",
-    "yargs": "^16.2.0"
+    "yargs": "^16.2.0",
+    "exifreader": "^4.1.0",
+    "xml2js": "^0.4.23"
   },
   "devDependencies": {
     "adm-zip": "",
diff --git a/bids-validator/tests/tsv.spec.js b/bids-validator/tests/tsv.spec.js
index ef94134d2..9a477f75f 100644
--- a/bids-validator/tests/tsv.spec.js
+++ b/bids-validator/tests/tsv.spec.js
@@ -685,4 +685,30 @@ describe('TSV', function() {
     let issues = validate.TSV.validateContRec([physio_file], {})
     assert(issues.length === 1 && issues[0].code === 133)
   })
+
+  // samples checks -----------------------------------------------------------
+
+  const samplesFile = {
+    name: 'samples.tsv',
+    relativePath: '/samples.tsv',
+  }
+
+  it('should return errors for each missing mandatory header in samples.tsv', () => {
+    const tsv = 'wrong_col\nsome_data\n'
+    validate.TSV.TSV(samplesFile, tsv, [], function(issues) {
+      expect(issues.length).toBe(3)
+      const codes = issues.map(x => x.code)
+      expect(codes.includes(216)).toBe(true)
+      expect(codes.includes(217)).toBe(true)
+      expect(codes.includes(218)).toBe(true)
+    })
+  })
+
+  it('should return an error for invalid sample_type samples.tsv', () => {
+    const tsv = 'sample_type\nbad\n'
+    validate.TSV.TSV(samplesFile, tsv, [], function(issues) {
+      const codes = issues.map(x => x.code)
+      expect(codes.includes(219)).toBe(true)
+    })
+  })
 })
diff --git a/bids-validator/utils/files/index.js b/bids-validator/utils/files/index.js
index 02e7f48b1..237b940aa 100644
--- a/bids-validator/utils/files/index.js
+++ b/bids-validator/utils/files/index.js
@@ -3,6 +3,8 @@ import FileAPI from './FileAPI'
 
 import newFile from './newFile'
 import readFile from './readFile'
+import readOMEFile from './readOMEFile'
+import readBuffer from './readBuffer'
 import readNiftiHeader from './readNiftiHeader'
 import readDir from './readDir'
 import potentialLocations from './potentialLocations'
@@ -21,6 +23,8 @@ export default {
   newFile,
   readFile,
   readDir,
+  readBuffer,
+  readOMEFile,
   readNiftiHeader,
   generateMergedSidecarDict,
   potentialLocations,
diff --git a/bids-validator/utils/files/readBuffer.js b/bids-validator/utils/files/readBuffer.js
new file mode 100644
index 000000000..732a50ae2
--- /dev/null
+++ b/bids-validator/utils/files/readBuffer.js
@@ -0,0 +1,23 @@
+import isNode from '../isNode'
+import fs from 'fs'
+
+const readBuffer = file => {
+  return new Promise((resolve, reject) => {
+    if (isNode) {
+      resolve(fs.readFileSync(file.path))
+    } else {
+      try {
+        const reader = new FileReader()
+        reader.onload = event => {
+          resolve(event.target.result)
+        }
+
+        reader.readAsArrayBuffer(file)
+      } catch (e) {
+        reject(e)
+      }
+    }
+  })
+}
+
+export default readBuffer
diff --git a/bids-validator/utils/files/readFile.js b/bids-validator/utils/files/readFile.js
index b0efb9bff..4f420d6c7 100644
--- a/bids-validator/utils/files/readFile.js
+++ b/bids-validator/utils/files/readFile.js
@@ -25,7 +25,11 @@ const checkEncoding = (file, data, cb) => {
 }
 
 /**
- * Read
+ * readFile
+ * @param {object | File} file - nodeJS fs file or browser File
+ * @param {boolean} annexed - is the file currently annexed?
+ * @param {string} dir - path to directory containing dataset. Only used if
+ *   annexed is true.
  *
  * A helper method for reading file contents.
  * Takes a file object and a callback and calls
@@ -39,12 +43,12 @@ const checkEncoding = (file, data, cb) => {
 function readFile(file, annexed, dir) {
   return new Promise((resolve, reject) => {
     if (isNode) {
-      testFile(file, annexed, dir, function (issue, stats, remoteBuffer) {
+      testFile(file, annexed, dir, function(issue, stats, remoteBuffer) {
         if (issue) {
           return reject(issue)
         }
         if (!remoteBuffer) {
-          fs.readFile(file.path, function (err, data) {
+          fs.readFile(file.path, function(err, data) {
             if (err) {
               return reject(err)
             }
diff --git a/bids-validator/utils/files/readOMEFile.js b/bids-validator/utils/files/readOMEFile.js
new file mode 100644
index 000000000..bdbc2ac56
--- /dev/null
+++ b/bids-validator/utils/files/readOMEFile.js
@@ -0,0 +1,17 @@
+import ExifReader from 'exifreader'
+const xml2js = require('xml2js')
+
+const readOMEFile = buffer => {
+  let tags = ExifReader.load(buffer)
+  let xml = tags['ImageDescription']['description']
+  return new Promise((resolve, reject) => {
+    xml2js
+      .parseStringPromise(xml)
+      .then(result => {
+        resolve(result)
+      })
+      .catch(error => reject(error))
+  })
+}
+
+export default readOMEFile
diff --git a/bids-validator/utils/issues/list.js b/bids-validator/utils/issues/list.js
index 8b395b12c..1c17b2dc3 100644
--- a/bids-validator/utils/issues/list.js
+++ b/bids-validator/utils/issues/list.js
@@ -1042,4 +1042,80 @@ export default {
     reason:
       'The recommended file /README is very small. Please consider expanding it with additional information about the dataset.',
   },
+  214: {
+    key: 'SAMPLES_TSV_MISSING',
+    severity: 'error',
+    reason:
+      'The compulsory file /samples.tsv is missing. See Section 03 (Modality agnostic files) of the BIDS specification.',
+  },
+  215: {
+    key: 'SAMPLE_ID_PATTERN',
+    severity: 'error',
+    reason:
+      'sample_id column labels must consist of the pattern "sample-<sample_id>".',
+  },
+  216: {
+    key: 'SAMPLE_ID_COLUMN',
+    severity: 'error',
+    reason: "Samples .tsv files must have a 'sample_id' column.",
+  },
+  217: {
+    key: 'PARTICIPANT_ID_COLUMN',
+    severity: 'error',
+    reason: "Samples .tsv files must have a 'participant_id' column.",
+  },
+  218: {
+    key: 'SAMPLE_TYPE_COLUMN',
+    severity: 'error',
+    reason: "Samples .tsv files must have a 'sample_type' column.",
+  },
+  219: {
+    key: 'SAMPLE_TYPE_VALUE',
+    severity: 'error',
+    reason:
+      'sample_type MUST consist of one of the following values: cell line, in vitro differentiated cells, primary cell, cell-free sample, cloning host, tissue, whole organisms, organoid or technical sample.',
+  },
+  220: {
+    key: 'SAMPLE_ID_DUPLICATE',
+    severity: 'error',
+    reason:
+      'Each sample from a same subject MUST be described by one and only one row.',
+  },
+  221: {
+    key: 'PIXEL_SIZE_INCONSISTENT',
+    severity: 'error',
+    reason:
+      'PixelSize need to be consistent with PhysicalSizeX, PhysicalSizeY and PhysicalSizeZ OME metadata fields',
+  },
+  222: {
+    key: 'INVALID_PIXEL_SIZE_UNIT',
+    severity: 'warning',
+    reason: 'PixelSize consistency is only validated for "mm", "µm" and "nm".',
+  },
+  223: {
+    key: 'CHUNK_TRANSFORMATION_MATRIX_MISSING',
+    severity: 'warning',
+    reason:
+      "It is recommended to define 'ChunkTransformationMatrix' for this file.",
+  },
+  224: {
+    key: 'OPTIONAL_FIELD_INCONSISTENT',
+    severity: 'error',
+    reason: 'Optional JSON field is not consistent with the OME-TIFF metadata',
+  },
+  225: {
+    key: 'NO_VALID_JSON',
+    severity: 'error',
+    reason: 'No valid JSON file found for this file',
+  },
+  226: {
+    key: 'UNSUPPORTED_BIG_TIFF',
+    severity: 'warning',
+    reason: 'Metadata consistency check skipped for BigTiff OME-TIFF file',
+  },
+  227: {
+    key: 'INCONSISTENT_TIFF_EXTENSION',
+    severity: 'error',
+    reason: 'Inconsistent TIFF file type and extension',
+  },
 }
diff --git a/bids-validator/utils/summary/collectModalities.js b/bids-validator/utils/summary/collectModalities.js
index 4d0b3a903..7d95cee38 100644
--- a/bids-validator/utils/summary/collectModalities.js
+++ b/bids-validator/utils/summary/collectModalities.js
@@ -7,6 +7,7 @@ export const collectModalities = filenames => {
     MEG: 0,
     EEG: 0,
     iEEG: 0,
+    Microscopy: 0,
   }
   const secondary = {
     MRI_Diffusion: 0,
@@ -56,6 +57,9 @@ export const collectModalities = filenames => {
     if (type.file.isIEEG(path)) {
       modalities.iEEG++
     }
+    if (type.file.isMicroscopy(path)) {
+      modalities.Microscopy++
+    }
   }
   // Order by matching file count
   const nonZero = Object.keys(modalities).filter(a => modalities[a] !== 0)
diff --git a/bids-validator/utils/type.js b/bids-validator/utils/type.js
index d6199c999..0c15168e5 100644
--- a/bids-validator/utils/type.js
+++ b/bids-validator/utils/type.js
@@ -59,6 +59,9 @@ const megCrosstalkData = buildRegExp(file_level_rules.meg_crosstalk)
 const stimuliData = buildRegExp(file_level_rules.stimuli)
 const petData = buildRegExp(file_level_rules.pet)
 const petBlood = buildRegExp(file_level_rules.pet_blood)
+const microscopyData = buildRegExp(file_level_rules.microscopy)
+const microscopyPhotoData = buildRegExp(file_level_rules.microscopy_photo)
+const microscopyJSON = buildRegExp(file_level_rules.microscopy_json)
 // Phenotypic data
 const phenotypicData = buildRegExp(phenotypic_rules.phenotypic_data)
 // Session level
@@ -71,6 +74,7 @@ const ieegSes = buildRegExp(session_level_rules.ieeg_ses)
 const megSes = buildRegExp(session_level_rules.meg_ses)
 const scansSes = buildRegExp(session_level_rules.scans)
 const petSes = buildRegExp(session_level_rules.pet_ses)
+const microscopySes = buildRegExp(session_level_rules.microscopy_ses)
 // Subject level
 const subjectLevel = buildRegExp(subject_level_rules.subject_level)
 // Top level
@@ -85,6 +89,7 @@ const multiDirFieldmap = buildRegExp(top_level_rules.multi_dir_fieldmap)
 const otherTopFiles = buildRegExp(top_level_rules.other_top_files)
 const megTop = buildRegExp(top_level_rules.meg_top)
 const petTop = buildRegExp(top_level_rules.pet_top)
+const microscopyTop = buildRegExp(top_level_rules.microscopy_top)
 
 export default {
   /**
@@ -110,7 +115,9 @@ export default {
       this.file.isFieldMap(path) ||
       this.file.isPhenotypic(path) ||
       this.file.isPET(path) ||
-      this.file.isPETBlood(path)
+      this.file.isPETBlood(path) ||
+      this.file.isMicroscopy(path) ||
+      this.file.isMicroscopyJSON(path)
     )
   },
 
@@ -134,7 +141,8 @@ export default {
           megTop.test(path) ||
           eegTop.test(path) ||
           ieegTop.test(path) ||
-          petTop.test(path)
+          petTop.test(path) ||
+          microscopyTop.test(path)
         )
       } else {
         return (
@@ -148,7 +156,8 @@ export default {
           megTop.test(path) ||
           eegTop.test(path) ||
           ieegTop.test(path) ||
-          petTop.test(path)
+          petTop.test(path) ||
+          microscopyTop.test(path)
         )
       }
     },
@@ -203,7 +212,8 @@ export default {
         conditionalMatch(megSes, path) ||
         conditionalMatch(eegSes, path) ||
         conditionalMatch(ieegSes, path) ||
-        conditionalMatch(petSes, path)
+        conditionalMatch(petSes, path) ||
+        conditionalMatch(microscopySes, path)
       )
     },
 
@@ -339,6 +349,17 @@ export default {
       }
     },
 
+    isMicroscopy: function(path) {
+      return (
+        conditionalMatch(microscopyData, path) ||
+        conditionalMatch(microscopyPhotoData, path)
+      )
+    },
+
+    isMicroscopyJSON: function(path) {
+      return conditionalMatch(microscopyJSON, path)
+    },
+
     isBehavioral: function(path) {
       if (bids_schema) {
         return bids_schema.datatypes['beh'].some(regex => regex.exec(path))
@@ -365,7 +386,9 @@ export default {
         this.isBehavioral(path) ||
         this.isFuncBold(path) ||
         this.isPET(path) ||
-        this.isPETBlood(path)
+        this.isPETBlood(path) ||
+        this.isMicroscopy(path) ||
+        this.isMicroscopyJSON(path)
       )
     },
   },
diff --git a/bids-validator/validators/bids/fullTest.js b/bids-validator/validators/bids/fullTest.js
index a9c4d240f..41c4cff88 100644
--- a/bids-validator/validators/bids/fullTest.js
+++ b/bids-validator/validators/bids/fullTest.js
@@ -6,6 +6,7 @@ import json from '../json'
 import NIFTI from '../nifti'
 import bval from '../bval'
 import bvec from '../bvec'
+import ometiff from '../microscopy'
 import Events from '../events'
 import { session } from '../session'
 import checkAnyDataPresent from '../checkAnyDataPresent'
@@ -22,7 +23,7 @@ import collectPetFields from '../../utils/summary/collectPetFields'
 /**
  * Full Test
  *
- * Takes on an array of files, callback, and boolean inidicating if git-annex is used.
+ * Takes on an array of files, callback, and boolean indicating if git-annex is used.
  * Starts the validation process for a BIDS package.
  */
 const fullTest = (fileList, options, annexed, dir, schema, callback) => {
@@ -140,11 +141,29 @@ const fullTest = (fileList, options, annexed, dir, schema, callback) => {
       const readmeIssues = checkReadme(fileList)
       self.issues = self.issues.concat(readmeIssues)
 
+      // Check for samples file in the proper place (only for the microscopy modality)
+      if (summary.modalities.includes('Microscopy')) {
+        const samplesIssues = ometiff.checkSamples(fileList)
+        const jsonAndFieldIssues = ometiff.checkJSONAndField(
+          files,
+          jsonContentsDict,
+        )
+
+        self.issues = self.issues
+          .concat(samplesIssues)
+          .concat(jsonAndFieldIssues)
+      }
       // Validate json files and contents
       return json.validate(jsonFiles, fileList, jsonContentsDict, summary)
     })
     .then(jsonIssues => {
       self.issues = self.issues.concat(jsonIssues)
+
+      // ome-tiff consistency check
+      return ometiff.validate(files.ome, jsonContentsDict)
+    })
+    .then(omeIssues => {
+      self.issues = self.issues.concat(omeIssues)
       // Nifti validation
       return NIFTI.validate(
         files.nifti,
diff --git a/bids-validator/validators/bids/groupFileTypes.js b/bids-validator/validators/bids/groupFileTypes.js
index 42c4a1bb3..b76eca201 100644
--- a/bids-validator/validators/bids/groupFileTypes.js
+++ b/bids-validator/validators/bids/groupFileTypes.js
@@ -11,6 +11,9 @@ const groupFileTypes = (fileList, options) => {
     bvec: [],
     contRecord: [],
     invalid: [],
+    ome: [],
+    png: [],
+    tif: [],
     // used to check all files not already passed through testFile()
     misc: [],
   }
@@ -52,6 +55,17 @@ const sortFiles = (fileList, options, files) => {
       files.misc.push(file)
     } else if (ofType(filename, 'tsv.gz')) {
       files.contRecord.push(file)
+    } else if (ofType(filename, 'ome.tif') || ofType(filename, 'ome.btf')) {
+      // collect ome-tiff
+      files.ome.push(file)
+    } else if (ofType(filename, 'png')) {
+      files.png.push(file)
+    } else if (
+      ofType(filename, 'tif') &&
+      !ofType(filename, 'ome.tif') &&
+      !ofType(filename, 'ome.btf')
+    ) {
+      files.tif.push(file)
     } else {
       files.misc.push(file)
     }
diff --git a/bids-validator/validators/json/json.js b/bids-validator/validators/json/json.js
index d38493ecb..0401435c9 100644
--- a/bids-validator/validators/json/json.js
+++ b/bids-validator/validators/json/json.js
@@ -96,6 +96,26 @@ const selectSchema = file => {
       schema = require('./schemas/ieeg.json')
     } else if (file.name.endsWith('eeg.json')) {
       schema = require('./schemas/eeg.json')
+    } else if (
+      file.name.endsWith('TEM.json') ||
+      file.name.endsWith('SEM.json') ||
+      file.name.endsWith('uCT.json') ||
+      file.name.endsWith('BF.json') ||
+      file.name.endsWith('DF.json') ||
+      file.name.endsWith('PC.json') ||
+      file.name.endsWith('DIC.json') ||
+      file.name.endsWith('FLUO.json') ||
+      file.name.endsWith('CONF.json') ||
+      file.name.endsWith('PLI.json') ||
+      file.name.endsWith('CARS.json') ||
+      file.name.endsWith('2PE.json') ||
+      file.name.endsWith('MPE.json') ||
+      file.name.endsWith('SR.json') ||
+      file.name.endsWith('NLO.json') ||
+      file.name.endsWith('OCT.json') ||
+      file.name.endsWith('SPIM.json')
+      ) {
+      schema = require('./schemas/microscopy.json')
     } else if (
       file.relativePath.includes('/meg/') &&
       file.name.endsWith('coordsystem.json')
diff --git a/bids-validator/validators/json/schemas/microscopy.json b/bids-validator/validators/json/schemas/microscopy.json
new file mode 100644
index 000000000..4231f0ba9
--- /dev/null
+++ b/bids-validator/validators/json/schemas/microscopy.json
@@ -0,0 +1,83 @@
+{
+  "type": "object",
+  "properties": {
+    "Manufacturer": { "type": "string", "minLength": 1 },
+    "ManufacturersModelName": { "type": "string", "minLength": 1 },
+    "DeviceSerialNumber": {"type": "string", "minLength": 1},
+    "StationName": { "type": "string", "minLength": 1 },
+    "SoftwareVersions": { "type": "string", "minLength": 1 },
+    "InstitutionName": { "type": "string", "minLength": 1 },
+    "InstitutionAddress": { "type": "string", "minLength": 1 },  
+    "InstitutionalDepartmentName": { "type": "string", "minLength": 1 }, 
+    "BodyPart": { "type": "string", "minLength": 1 },
+    "BodyPartDetails": { "type": "string", "minLength": 1 },
+    "BodyPartDetailsOntology": { "type": "string", "minLength": 1, "format": "uri" },
+    "SampleEnvironment": { "type": "string", "minLength": 1, "enum": ["in vivo", "ex vivo", "in vitro"]  },
+    "SampleEmbedding": { "type": "string", "minLength": 1 },
+    "SampleFixation": { "type": "string", "minLength": 1 },
+    "SampleStaining": { 
+      "anyOf": [
+        { "type": "string", "minLength": 1 },
+        { "type": "array", "items": { "type": "string" } }
+      ]
+    },
+    "SamplePrimaryAntibody": { 
+      "anyOf": [
+        { "type": "string", "minLength": 1 },
+        { "type": "array", "items": { "type": "string" } }
+      ]
+    },
+    "SampleSecondaryAntibody": { 
+      "anyOf": [
+        { "type": "string", "minLength": 1 },
+        { "type": "array", "items": { "type": "string" } }
+      ]
+    },
+    "SliceThickness": { "type": "number", "exclusiveMinimum": 0 },
+    "SampleExtractionProtocol": { "type": "string", "minLength": 1 },
+    "SampleExtractionInstitution": { "type": "string", "minLength": 1 },
+    "TissueDeformationScaling": { "type": "number" },
+    "PixelSize": {"type": "array", "minItems": 2, "maxItems": 3, "items": { "type": "number", "minimum": 0 } },
+    "PixelSizeUnits": { "type": "string", "enum": ["mm", "um", "nm"] },
+    "Immersion": { "type": "string", "minLength": 1 },
+    "NumericalAperture": { "type": "number", "exclusiveMinimum": 0 },
+    "Magnification": { "type": "number", "exclusiveMinimum": 0 },
+    "ImageAcquisitionProtocol": { "type": "string", "minLength": 1 },
+    "OtherAcquisitionParameters": { "type": "string", "minLength": 1 },
+    "ChunkTransformationMatrix": {
+      "anyOf": [
+        {"type": "array", "minItems": 3, "maxItems": 3, "items": { "type": "array", "minItems": 3, "maxItems": 3, "items":{ "type": "number"} } },
+        {"type": "array", "minItems": 4, "maxItems": 4, "items": { "type": "array", "minItems": 4, "maxItems": 4, "items":{ "type": "number"} } }
+      ]
+    },
+    "ChunkTransformationMatrixAxis": { "type": "array", "minItems": 2, "maxItems": 3, "items": { "type": "string" }}
+    },
+
+  "required": [
+    "PixelSize",
+    "PixelSizeUnits"
+  ],
+
+  "recommended": [
+    "Manufacturer",
+    "ManufacturersModelName",
+    "DeviceSerialNumber",
+    "StationName",
+    "SoftwareVersions",
+    "InstitutionName",
+    "InstitutionAddress",
+    "InstitutionalDepartmentName",
+    "BodyPart",
+    "BodyPartDetails",
+    "SampleEnvironment",
+    "SampleStaining",
+    "SamplePrimaryAntibody",
+    "SampleSecondaryAntibody"
+  ],
+
+  "dependencies": {
+    "PixelSize": ["PixelSizeUnits"],
+    "ChunkTransformationMatrix": ["ChunkTransformationMatrixAxis"]
+  }
+
+}
diff --git a/bids-validator/validators/microscopy/__tests__/checkJSONAndField.spec.js b/bids-validator/validators/microscopy/__tests__/checkJSONAndField.spec.js
new file mode 100644
index 000000000..62fa586b5
--- /dev/null
+++ b/bids-validator/validators/microscopy/__tests__/checkJSONAndField.spec.js
@@ -0,0 +1,51 @@
+import { assert } from 'chai'
+import checkJSONAndField from '../checkJSONAndField'
+
+describe('checkJSONAndField()', () => {
+  const emptyJsonContentsDict = {
+    'test.json': {},
+  }
+  it('returns no issues with empty arguments', () => {
+    const issues = checkJSONAndField({}, {})
+    expect(issues.length).toBe(0)
+  })
+
+  it('returns issue 225 with no json for ome files', () => {
+    const files = {
+      ome: [{ relativePath: 'test.ome.tif' }],
+    }
+    const issues = checkJSONAndField(files, emptyJsonContentsDict)
+    expect(issues.length).toBe(1)
+    expect(issues[0].code).toBe(225)
+  })
+
+  it('returns issue 225 with no json for tif files', () => {
+    const files = {
+      tif: [{ relativePath: 'test.tif' }],
+    }
+    const issues = checkJSONAndField(files, emptyJsonContentsDict)
+    expect(issues.length).toBe(1)
+    expect(issues[0].code).toBe(225)
+  })
+
+  it('returns issue 225 with no json for png files', () => {
+    const files = {
+      png: [{ relativePath: 'test.png' }],
+    }
+    const issues = checkJSONAndField(files, emptyJsonContentsDict)
+    expect(issues.length).toBe(1)
+    expect(issues[0].code).toBe(225)
+  })
+
+  it('returns warning 223 if chunk entity present but missing metadata', () => {
+    const files = {
+      ome: [{ relativePath: '/test_chunk-01.ome.tif' }],
+    }
+    const jsonContentsDict = {
+      '/test_chunk-01.json': { testKey: 'testValue' },
+    }
+    const issues = checkJSONAndField(files, jsonContentsDict)
+    expect(issues.length).toBe(1)
+    expect(issues[0].code).toBe(223)
+  })
+})
diff --git a/bids-validator/validators/microscopy/__tests__/checkSample.spec.js b/bids-validator/validators/microscopy/__tests__/checkSample.spec.js
new file mode 100644
index 000000000..5dd541c27
--- /dev/null
+++ b/bids-validator/validators/microscopy/__tests__/checkSample.spec.js
@@ -0,0 +1,19 @@
+import checkSamples from '../checkSamples'
+describe('checkSamples()', () => {
+  it('returns issue 214 when no samples.tsv is present', () => {
+    const fileList = {
+      '0': { relativePath: '/test.tsv' },
+    }
+    const issues = checkSamples(fileList)
+    expect(issues.length).toBe(1)
+    expect(issues[0].code).toBe(214)
+  })
+
+  it('doesnt return issue 214 when samples.tsv is present', () => {
+    const fileList = {
+      '0': { relativePath: '/samples.tsv' },
+    }
+    const issues = checkSamples(fileList)
+    expect(issues.length).toBe(0)
+  })
+})
diff --git a/bids-validator/validators/microscopy/__tests__/data/btif_id.ome.tif b/bids-validator/validators/microscopy/__tests__/data/btif_id.ome.tif
new file mode 100644
index 000000000..f62946161
Binary files /dev/null and b/bids-validator/validators/microscopy/__tests__/data/btif_id.ome.tif differ
diff --git a/bids-validator/validators/microscopy/__tests__/data/invalid_id.ome.tif b/bids-validator/validators/microscopy/__tests__/data/invalid_id.ome.tif
new file mode 100644
index 000000000..96973db51
Binary files /dev/null and b/bids-validator/validators/microscopy/__tests__/data/invalid_id.ome.tif differ
diff --git a/bids-validator/validators/microscopy/__tests__/data/tif_id.ome.btf b/bids-validator/validators/microscopy/__tests__/data/tif_id.ome.btf
new file mode 100644
index 000000000..416a1d8ec
Binary files /dev/null and b/bids-validator/validators/microscopy/__tests__/data/tif_id.ome.btf differ
diff --git a/bids-validator/validators/microscopy/__tests__/data/tif_id.ome.tif b/bids-validator/validators/microscopy/__tests__/data/tif_id.ome.tif
new file mode 100644
index 000000000..416a1d8ec
Binary files /dev/null and b/bids-validator/validators/microscopy/__tests__/data/tif_id.ome.tif differ
diff --git a/bids-validator/validators/microscopy/__tests__/data/valid.ome.tif b/bids-validator/validators/microscopy/__tests__/data/valid.ome.tif
new file mode 100644
index 000000000..416a1d8ec
Binary files /dev/null and b/bids-validator/validators/microscopy/__tests__/data/valid.ome.tif differ
diff --git a/bids-validator/validators/microscopy/__tests__/validate.spec.js b/bids-validator/validators/microscopy/__tests__/validate.spec.js
new file mode 100644
index 000000000..2bf7a59f2
--- /dev/null
+++ b/bids-validator/validators/microscopy/__tests__/validate.spec.js
@@ -0,0 +1,99 @@
+import path from 'path'
+
+import readDir from '../../../utils/files/readDir'
+import validate from '../validate'
+
+const dataDir = path.join(__dirname, '/data')
+
+const jsonContent = {
+  Manufacturer: 'Miltenyi Biotec',
+  ManufacturersModelName: 'UltraMicroscope II',
+  BodyPart: 'CSPINE',
+  SampleEnvironment: 'ex vivo',
+  SampleFixation: '4% paraformaldehyde, 2% glutaraldehyde',
+  SampleStaining: 'Luxol fast blue',
+  PixelSize: [1, 1, 1],
+  PixelSizeUnits: 'um',
+  Immersion: 'Oil',
+  NumericalAperture: 1.4,
+  Magnification: 40,
+  ChunkTransformationMatrix: [
+    [1, 0, 0, 0],
+    [0, 2, 0, 0],
+    [0, 0, 1, 0],
+    [0, 0, 0, 1],
+  ],
+  ChunkTransformationMatrixAxis: ['X', 'Y', 'Z'],
+}
+
+describe('validate', () => {
+  it('returns error 227 with extension/id mismatch', () => {
+    const fileName = 'btif_id.ome.tif'
+    const files = [
+      {
+        name: fileName,
+        relativePath: `/bids-validator/validators/microscopy/__tests__/data/${fileName}`,
+        path: path.join(dataDir, fileName),
+      },
+    ]
+
+    expect.assertions(3)
+    return validate(files, {}).then(issues => {
+      expect(issues.length).toBe(2)
+      expect(issues[0].code).toBe(227)
+      expect(issues[1].code).toBe(226)
+    })
+  })
+
+  it('returns error 227 with incorrect id in magic number', () => {
+    const fileName = 'invalid_id.ome.tif'
+    const files = [
+      {
+        name: fileName,
+        relativePath: `/bids-validator/validators/microscopy/__tests__/data/${fileName}`,
+        path: path.join(dataDir, fileName),
+      },
+    ]
+    expect.assertions(2)
+    return validate(files, {}).then(issues => {
+      expect(issues.length).toBe(1)
+      expect(issues[0].code).toBe(227)
+    })
+  })
+
+  it('returns error 227 with tif id and btf extension', () => {
+    const fileName = 'tif_id.ome.btf'
+    const files = [
+      {
+        name: fileName,
+        relativePath: `/bids-validator/validators/microscopy/__tests__/data/${fileName}`,
+        path: path.join(dataDir, fileName),
+      },
+    ]
+
+    expect.assertions(2)
+    return validate(files, {}).then(issues => {
+      expect(issues.length).toBe(1)
+      expect(issues[0].code).toBe(227)
+    })
+  })
+
+  it('validates with valid data', () => {
+    const fileName = 'valid.ome.tif'
+    const relativePath = `/bids-validator/validators/microscopy/__tests__/data/${fileName}`
+    const files = [
+      {
+        name: fileName,
+        relativePath: relativePath,
+        path: path.join(dataDir, fileName),
+      },
+    ]
+    const jsonContentDict = {}
+    jsonContentDict[relativePath.replace('.ome.tif', '.json')] = jsonContent
+
+    expect.assertions(1)
+    return validate(files, jsonContentDict).then(issues => {
+      expect(issues.length).toBe(0)
+    })
+  })
+})
diff --git a/bids-validator/validators/microscopy/checkJSONAndField.js b/bids-validator/validators/microscopy/checkJSONAndField.js
new file mode 100644
index 000000000..266f3481e
--- /dev/null
+++ b/bids-validator/validators/microscopy/checkJSONAndField.js
@@ -0,0 +1,85 @@
+import utils from '../../utils'
+const Issue = utils.issues.Issue
+
+const checkJSONAndField = (files, jsonContentsDict) => {
+  let issues = []
+  if (files.ome) {
+    files.ome.forEach(file => {
+      let possibleJsonPath = file.relativePath
+        .replace('.tif', '')
+        .replace('.btf', '')
+        .replace('.ome', '.json')
+      issues = issues.concat(
+        ifJsonExist(file, possibleJsonPath, jsonContentsDict),
+      )
+    })
+  }
+  if (files.png) {
+    files.png.forEach(file => {
+      if (!file.relativePath.includes('_photo')) {
+        let possibleJsonPath = file.relativePath.replace('.png', '.json')
+        issues = issues.concat(
+          ifJsonExist(file, possibleJsonPath, jsonContentsDict),
+        )
+      }
+    })
+  }
+  if (files.tif) {
+    files.tif.forEach(file => {
+      if (!file.relativePath.includes('_photo')) {
+        let possibleJsonPath = file.relativePath.replace('.tif', '.json')
+        issues = issues.concat(
+          ifJsonExist(file, possibleJsonPath, jsonContentsDict),
+        )
+      }
+    })
+  }
+  return issues
+}
+
+const ifJsonExist = (file, possibleJsonPath, jsonContentsDict) => {
+  let potentialSidecars = utils.files.potentialLocations(possibleJsonPath)
+  const chunkRegex = new RegExp('_chunk-[0-9]+')
+
+  const jsonChunkFiles = potentialSidecars.filter(
+    name => jsonContentsDict.hasOwnProperty(name) && chunkRegex.exec(name),
+  )
+  const chunkPresent =
+    jsonChunkFiles.length || chunkRegex.exec(file.relativePath)
+
+  const mergedDictionary = utils.files.generateMergedSidecarDict(
+    potentialSidecars,
+    jsonContentsDict,
+  )
+
+  // check if the given file has a corresponding JSON file
+  if (Object.keys(mergedDictionary).length === 0) {
+    return [
+      new Issue({
+        file: file,
+        code: 225,
+      }),
+    ]
+  }
+
+  if (chunkPresent) {
+    return checkMatrixField(file, mergedDictionary)
+  }
+  
+  return []
+}
+
+const checkMatrixField = (file, mergedDictionary) => {
+  let issues = []
+  if (!mergedDictionary.hasOwnProperty('ChunkTransformationMatrix')) {
+    issues.push(
+      new Issue({
+        file: file,
+        code: 223,
+      }),
+    )
+  }
+  return issues
+}
+
+export default checkJSONAndField
diff --git a/bids-validator/validators/microscopy/checkSamples.js b/bids-validator/validators/microscopy/checkSamples.js
new file mode 100644
index 000000000..c535a8053
--- /dev/null
+++ b/bids-validator/validators/microscopy/checkSamples.js
@@ -0,0 +1,16 @@
+import isNode from '../../utils/isNode'
+
+const Issue = require('../../utils').issues.Issue
+
+const checkSamples = fileList => {
+  const issues = []
+  const fileKeys = Object.keys(fileList)
+  const samplesFile = Array.from(Object.values(fileList)).find(
+    file => file.relativePath && file.relativePath == '/samples.tsv',
+  )
+  if (!samplesFile) {
+    issues.push(new Issue({ code: 214 }))
+  }
+  return issues
+}
+export default checkSamples
diff --git a/bids-validator/validators/microscopy/index.js b/bids-validator/validators/microscopy/index.js
new file mode 100644
index 000000000..ab3895a9c
--- /dev/null
+++ b/bids-validator/validators/microscopy/index.js
@@ -0,0 +1,11 @@
+import ometiff from './ometiff'
+import validate from './validate'
+import checkSamples from './checkSamples'
+import checkJSONAndField from './checkJSONAndField'
+
+export default {
+  ometiff,
+  validate,
+  checkSamples,
+  checkJSONAndField,
+}
diff --git a/bids-validator/validators/microscopy/ometiff.js b/bids-validator/validators/microscopy/ometiff.js
new file mode 100644
index 000000000..6e6030375
--- /dev/null
+++ b/bids-validator/validators/microscopy/ometiff.js
@@ -0,0 +1,165 @@
+import utils from '../../utils'
+const Issue = utils.issues.Issue
+
+/**
+ * ometiff
+ *
+ * Takes an ometiff file, its omedata as an object
+ * and a callback as arguments. Callback
+ * with any issues it finds while validating
+ * against the BIDS specification.
+ */
+export default function ometiff(file, omeData, jsonContentsDict, callback) {
+  let issues = []
+
+  let mergedDictionary = getMergedDictionary(file, jsonContentsDict)
+
+  let rootKey = Object.keys(omeData)[0]
+  let namespace = ''
+  if (rootKey.includes(':OME')) {
+    namespace = rootKey.split(':OME')[0].concat(':')
+  }
+
+  // Check for consistency with optional OME-TIFF metadata if present for
+  // Immersion, NumericalAperture and Magnification
+  let optionalFieldsIssues = checkOptionalFields(
+    file.relativePath,
+    omeData,
+    namespace,
+    mergedDictionary,
+  )
+
+  // Check for consistency for PixelSize between JSON and OME-TIFF metadata
+  let pixelSizeIssues = checkPixelSize(omeData, namespace, mergedDictionary)
+
+  issues = issues.concat(optionalFieldsIssues).concat(pixelSizeIssues)
+
+  callback(issues)
+}
+
+const convertFactor = (omeUnit, jsonUnit) => {
+  if (omeUnit === jsonUnit || (omeUnit === 'µm' && jsonUnit === 'um')) return 1
+
+  if (jsonUnit === 'um') {
+    if (omeUnit === 'mm') {
+      return 1000
+    } else if (omeUnit === 'nm') {
+      return 0.001
+    }
+  } else if (jsonUnit === 'mm') {
+    if (omeUnit === 'µm') {
+      return 0.001
+    } else if (omeUnit === 'nm') {
+      return 0.000001
+    }
+  } else if (jsonUnit === 'nm') {
+    if (omeUnit === 'mm') {
+      return 1000000
+    } else if (omeUnit === 'µm') {
+      return 1000
+    }
+  }
+}
+
+const getMergedDictionary = (file, jsonContentsDict) => {
+  let possibleJsonPath = file.relativePath
+    .replace('.tif', '')
+    .replace('.ome', '.json')
+
+  let potentialSidecars = utils.files.potentialLocations(possibleJsonPath)
+
+  return utils.files.generateMergedSidecarDict(
+    potentialSidecars,
+    jsonContentsDict,
+  )
+}
+
+const checkOptionalFields = (omePath, omeData, namespace, jsonData) => {
+  let issues = []
+
+  let fields = {
+    Immersion: 'Immersion',
+    NumericalAperture: 'LensNA',
+    Magnification: 'NominalMagnification',
+  }
+
+  if (
+    omeData[`${namespace}OME`][`${namespace}Instrument`] &&
+    omeData[`${namespace}OME`][`${namespace}Instrument`][0][`${namespace}Objective`]
+  ) {
+    let objective =
+      omeData[`${namespace}OME`][`${namespace}Instrument`][0][`${namespace}Objective`][0]['$']
+    for (let field in fields) {
+      let property = fields[field]
+      if (jsonData.hasOwnProperty(field) && objective[property]) {
+        if (objective[property] != jsonData[field]) {
+          issues.push(
+            new Issue({
+              file: {
+                relativePath: omePath,
+                path: omePath,
+              },
+              evidence: `JSON field '${field}' is inconsistent`,
+              code: 224,
+            }),
+          )
+        }
+      }
+    }
+  }
+
+  return issues
+}
+
+const checkPixelSize = (omeData, namespace, jsonData) => {
+  let issues = []
+  let validUnits = ['um', 'µm', 'nm', 'mm']
+
+  const PhysicalSizeX =
+    omeData[`${namespace}OME`][`${namespace}Image`][0][`${namespace}Pixels`][0]['$']['PhysicalSizeX']
+  const physicalSizeXUnit =
+    omeData[`${namespace}OME`][`${namespace}Image`][0][`${namespace}Pixels`][0]['$']['PhysicalSizeXUnit']
+  const PhysicalSizeY =
+    omeData[`${namespace}OME`][`${namespace}Image`][0][`${namespace}Pixels`][0]['$']['PhysicalSizeY']
+  const physicalSizeYUnit =
+    omeData[`${namespace}OME`][`${namespace}Image`][0][`${namespace}Pixels`][0]['$']['PhysicalSizeYUnit']
+  const PhysicalSizeZ =
+    omeData[`${namespace}OME`][`${namespace}Image`][0][`${namespace}Pixels`][0]['$']['PhysicalSizeZ']
+  const physicalSizeZUnit =
+    omeData[`${namespace}OME`][`${namespace}Image`][0][`${namespace}Pixels`][0]['$']['PhysicalSizeZUnit']
+
+  // if no corresponding json file, skip the consistency check
+  if (Object.keys(jsonData).length === 0) return []
+
+  let unitsPendToCheck = [
+    physicalSizeXUnit,
+    physicalSizeYUnit,
+    physicalSizeZUnit,
+  ]
+
+  unitsPendToCheck.forEach(unit => {
+    if (!validUnits.includes(unit)) {
+      issues.push(new Issue({ code: 222 }))
+    }
+  })
+
+  // if any physicalSizeUnit is not valid or no valid json file, skip the consistency check
+  if (issues.length > 0) return issues
+
+  let pixelSize = jsonData['PixelSize']
+  let physicalSizeUnit = jsonData['PixelSizeUnits']
+
+  let factorX = convertFactor(physicalSizeXUnit, physicalSizeUnit)
+  let factorY = convertFactor(physicalSizeYUnit, physicalSizeUnit)
+  let factorZ = convertFactor(physicalSizeZUnit, physicalSizeUnit)
+
+  if (
+    PhysicalSizeX * factorX !== pixelSize[0] ||
+    PhysicalSizeY * factorY !== pixelSize[1] ||
+    PhysicalSizeZ * factorZ !== pixelSize[2]
+  ) {
+    issues.push(new Issue({ code: 221 }))
+  }
+
+  return issues
+}
diff --git a/bids-validator/validators/microscopy/validate.js b/bids-validator/validators/microscopy/validate.js
new file mode 100644
index 000000000..c4d90e97e
--- /dev/null
+++ b/bids-validator/validators/microscopy/validate.js
@@ -0,0 +1,75 @@
+import utils from '../../utils'
+const Issue = utils.issues.Issue
+import ometiff from './ometiff'
+import validateTiffSignature from './validateTiffSignature'
+
+const TIFF_ID = 0x2a
+const BIG_TIFF_ID = 0x2b
+
+const validate = (files, jsonContentsDict) => {
+  let issues = []
+  // validate ometiff
+  const omePromises = files.map(function(file) {
+    return utils.limit(
+      () =>
+        new Promise((resolve, reject) => {
+          utils.files.readBuffer(file).then(buffer => {
+            if (validateTiffSignature(buffer, TIFF_ID)) {
+              if (file.relativePath.endsWith('.ome.btf')) {
+                issues.push(
+                  new Issue({
+                    code: 227,
+                    file: file,
+                    evidence: `Inconsistent TIFF file type and extension, given .ome.btf but should be .ome.tif`,
+                  }),
+                )
+              }
+              utils.files
+                .readOMEFile(buffer)
+                .then(omeData => {
+                  ometiff(file, omeData, jsonContentsDict, function(omeIssues) {
+                    issues = issues.concat(omeIssues)
+                    resolve()
+                  })
+                })
+                .catch(err =>
+                  utils.issues.redirect(err, reject, () => {
+                    issues.push(err)
+                    resolve()
+                  }),
+                )
+            } else if (validateTiffSignature(buffer, BIG_TIFF_ID)) {
+              if (file.relativePath.endsWith('.ome.tif')) {
+                issues.push(
+                  new Issue({
+                    code: 227,
+                    file: file,
+                    evidence: `Inconsistent TIFF file type and extension, given .ome.tif but should be .ome.btf`,
+                  }),
+                )
+              }
+              issues.push(
+                new Issue({
+                  code: 226,
+                  file: file,
+                }),
+              )
+              resolve()
+            } else {
+              issues.push(
+                new Issue({
+                  code: 227,
+                  file: file,
+                  evidence: `3rd byte of file does not identify file as tiff.`,
+                }),
+              )
+              resolve()
+            }
+          })
+        }),
+    )
+  })
+  return Promise.all(omePromises).then(() => issues)
+}
+
+export default validate
diff --git a/bids-validator/validators/microscopy/validateTiffSignature.js b/bids-validator/validators/microscopy/validateTiffSignature.js
new file mode 100644
index 000000000..5ac7265b3
--- /dev/null
+++ b/bids-validator/validators/microscopy/validateTiffSignature.js
@@ -0,0 +1,20 @@
+import isNode from '../../utils/isNode'
+
+const getDataView = buffer => {
+  if (isNode) {
+    const uint8arr = new Uint8Array(buffer.byteLength)
+    buffer.copy(uint8arr, 0, 0, buffer.byteLength)
+    return new DataView(uint8arr.buffer)
+  } else {
+    return new DataView(buffer)
+  }
+}
+
+const validateTiffSignature = (buffer, tiffId) => {
+  const dataView = getDataView(buffer)
+  const littleEndian = dataView.getUint16(0) === 0x4949
+
+  return dataView.getUint16(2, littleEndian) === tiffId
+}
+
+export default validateTiffSignature
diff --git a/bids-validator/validators/tsv/tsv.js b/bids-validator/validators/tsv/tsv.js
index 098d427cd..bca199b15 100644
--- a/bids-validator/validators/tsv/tsv.js
+++ b/bids-validator/validators/tsv/tsv.js
@@ -222,8 +222,9 @@ const TSV = (file, contents, fileList, callback) => {
             new Issue({
               file: file,
               evidence: headersEvidence(headers),
-              reason: 'Participant_id column should be named ' +
-                      'as sub-<subject_id>.',
+              reason:
+                'Participant_id column should be named ' +
+                'as sub-<subject_id>.',
               line: l,
               code: 212,
             }),
@@ -240,6 +241,168 @@ const TSV = (file, contents, fileList, callback) => {
     }
   }
 
+  // samples.tsv
+  let samples = null
+  if (file.name === 'samples.tsv') {
+    const sampleIssues = []
+    const sampleIdColumnValues = []
+    const participantIdColumnValues = []
+    const sampleIdColumn = headers.indexOf('sample_id')
+    const participantIdColumn = headers.indexOf('participant_id')
+    const sampleTypeColumn = headers.indexOf('sample_type')
+
+    // if the sample_id column is missing, an error
+    // will be raised
+    if (sampleIdColumn === -1) {
+      sampleIssues.push(
+        new Issue({
+          file: file,
+          evidence: headersEvidence(headers),
+          line: 1,
+          code: 216,
+        }),
+      )
+    }
+    // if the participant_id column is missing, an error
+    // will be raised
+    if (participantIdColumn === -1) {
+      sampleIssues.push(
+        new Issue({
+          file: file,
+          evidence: headersEvidence(headers),
+          line: 1,
+          code: 217,
+        }),
+      )
+    }
+    // if the sample_type column is missing, an error
+    // will be raised
+    if (sampleTypeColumn === -1) {
+      sampleIssues.push(
+        new Issue({
+          file: file,
+          evidence: headersEvidence(headers),
+          line: 1,
+          code: 218,
+        }),
+      )
+    }
+    // Fold sampleIssues into main issue array, only needed it for this
+    // conditional.
+    issues.push(...sampleIssues)
+    if (sampleIssues.length === 0) {
+      // otherwise, the samples should comprise of
+      // sample-<sample_id> and one sample per row
+      samples = []
+      for (let l = 1; l < rows.length; l++) {
+        const row = rows[l]
+        // skip empty rows
+        if (!row || /^\s*$/.test(row)) {
+          continue
+        }
+        sampleIdColumnValues.push(row[sampleIdColumn])
+
+        // check if any incorrect patterns in sample_id column
+        if (!row[sampleIdColumn].startsWith('sample-')) {
+          issues.push(
+            new Issue({
+              file: file,
+              evidence: row[sampleIdColumn],
+              reason:
+                'sample_id column should be named ' + 'as sample-<sample_id>.',
+              line: l,
+              code: 215,
+            }),
+          )
+        }
+      }
+      // The participants should comprise of
+      // sub-<subject_id> and one subject per row
+      participants = []
+      for (let l = 1; l < rows.length; l++) {
+        const row = rows[l]
+        // skip empty rows
+        if (!row || /^\s*$/.test(row)) {
+          continue
+        }
+        participantIdColumnValues.push(row[participantIdColumn])
+
+        // check if any incorrect patterns in participant_id column
+        if (!row[participantIdColumn].startsWith('sub-')) {
+          issues.push(
+            new Issue({
+              file: file,
+              evidence: row[participantIdColumn],
+              reason:
+                'Participant_id column should be named ' +
+                'as sub-<subject_id>.',
+              line: l,
+              code: 212,
+            }),
+          )
+        }
+
+        // obtain a list of the sample IDs in the samples.tsv file
+        const sample = row[sampleIdColumn].replace('sample-', '')
+        if (sample == 'emptyroom') {
+          continue
+        }
+        samples.push(sample)
+      }
+
+      // check if a sample from same subject is described by one and only one row
+      let samplePartIdsSet = new Set()
+      for (let r = 0; r < rows.length - 1; r++) {
+        let uniqueString = sampleIdColumnValues[r].concat(
+          participantIdColumnValues[r],
+        )
+        // check if SampleId Have Duplicate
+        if (samplePartIdsSet.has(uniqueString)) {
+          issues.push(
+            new Issue({
+              file: file,
+              evidence: sampleIdColumnValues,
+              reason:
+                'Each sample from a same subject MUST be described by one and only one row.',
+              line: 1,
+              code: 220,
+            }),
+          )
+          break
+        } else samplePartIdsSet.add(uniqueString)
+      }
+    }
+
+    if (sampleTypeColumn !== -1) {
+      // check if any incorrect patterns in sample_type column
+      const validSampleTypes = [
+        'cell line',
+        'in vitro differentiated cells',
+        'primary cell',
+        'cell-free sample',
+        'cloning host',
+        'tissue',
+        'whole organisms',
+        'organoid',
+        'technical sample',
+      ]
+      for (let c = 1; c < rows.length; c++) {
+        const row = rows[c]
+        if (!validSampleTypes.includes(row[sampleTypeColumn])) {
+          issues.push(
+            new Issue({
+              file: file,
+              evidence: row[sampleTypeColumn],
+              reason: "sample_type can't be any value.",
+              line: c + 1,
+              code: 219,
+            }),
+          )
+        }
+      }
+    }
+  }
+
   if (
     file.relativePath.includes('/meg/') &&
     file.name.endsWith('_channels.tsv')
@@ -298,10 +461,7 @@ const TSV = (file, contents, fileList, callback) => {
   }
 
   // blood.tsv
-  if (
-    file.relativePath.includes('/pet/') &&
-    file.name.endsWith('_blood.tsv')
-  ) {
+  if (file.relativePath.includes('/pet/') && file.name.endsWith('_blood.tsv')) {
     // Validate fields here
     checkheader('time', 0, file, 126)
   }
@@ -365,7 +525,7 @@ const TSV = (file, contents, fileList, callback) => {
           pathList.push(fDir)
         } else if (fPath.includes('_ieeg.mefd/')) {
           // MEF3 data
-          const fDir = fPath.substring(0, fPath.indexOf('_ieeg.mefd/') + 10);
+          const fDir = fPath.substring(0, fPath.indexOf('_ieeg.mefd/') + 10)
           if (!pathList.includes(fDir)) {
             pathList.push(fDir)
           }
@@ -415,5 +575,4 @@ const TSV = (file, contents, fileList, callback) => {
   }
   callback(issues, participants, stimPaths)
 }
-
 export default TSV
diff --git a/package-lock.json b/package-lock.json
index 52e3722d4..6b0d14546 100644
--- a/package-lock.json
+++ b/package-lock.json
@@ -19,7 +19,7 @@
       }
     },
     "bids-validator": {
-      "version": "1.8.9-dev.0",
+      "version": "1.8.10-dev.0",
       "license": "MIT",
       "dependencies": {
         "@aws-sdk/client-s3": "^3.9.0",
@@ -29,6 +29,7 @@
         "cross-fetch": "^3.0.6",
         "date-fns": "^2.7.0",
         "events": "^3.3.0",
+        "exifreader": "^4.1.0",
         "hed-validator": "^3.5.0",
         "ignore": "^4.0.2",
         "is-utf8": "^0.2.1",
@@ -43,6 +44,7 @@
         "semver": "^7.3.2",
         "stream-browserify": "^3.0.0",
         "table": "^5.2.3",
+        "xml2js": "^0.4.23",
         "yaml": "^1.10.2",
         "yargs": "^16.2.0"
       },
@@ -70,9 +72,10 @@
       }
     },
     "bids-validator-web": {
-      "version": "1.8.9-dev.0",
+      "version": "1.8.10-dev.0",
       "license": "MIT",
       "dependencies": {
+        "@babel/runtime": "^7.16.7",
         "bootstrap": "^4.3.0",
         "bowser": "^1.0.0",
         "next": "^11.1.2",
@@ -84,6 +87,17 @@
         "sass": "^1.32.8"
       }
     },
+    "bids-validator-web/node_modules/@babel/runtime": {
+      "version": "7.16.7",
+      "resolved": "https://registry.npmjs.org/@babel/runtime/-/runtime-7.16.7.tgz",
+      "integrity": "sha512-9E9FJowqAsytyOY6LG+1KuueckRL+aQW+mKvXRXnuFGyRAyepJPmEo9vgMfXUA6O9u3IeEdv9MAkppFcaQwogQ==",
+      "dependencies": {
+        "regenerator-runtime": "^0.13.4"
+      },
+      "engines": {
+        "node": ">=6.9.0"
+      }
+    },
     "bids-validator/node_modules/ansi-styles": {
       "version": "4.3.0",
       "resolved": "https://registry.npmjs.org/ansi-styles/-/ansi-styles-4.3.0.tgz",
@@ -6568,6 +6582,15 @@
       "integrity": "sha512-7tFImggNeNBVMsn0vLrpn1H1uPrUBdnARPTpZoitY37ZrdJREzf7I16tMrlK3hen349gr1NYh8CmZQa7CTG6Aw==",
       "dev": true
     },
+    "node_modules/@xmldom/xmldom": {
+      "version": "0.7.5",
+      "resolved": "https://registry.npmjs.org/@xmldom/xmldom/-/xmldom-0.7.5.tgz",
+      "integrity": "sha512-V3BIhmY36fXZ1OtVcI9W+FxQqxVLsPKcNjWigIaa81dLC9IolJl5Mt4Cvhmr0flUnjSpTdrbMTSbXqYqV5dT6A==",
+      "optional": true,
+      "engines": {
+        "node": ">=10.0.0"
+      }
+    },
     "node_modules/abab": {
       "version": "2.0.5",
       "resolved": "https://registry.npmjs.org/abab/-/abab-2.0.5.tgz",
@@ -9833,6 +9856,15 @@
         "url": "https://github.com/sindresorhus/execa?sponsor=1"
       }
     },
+    "node_modules/exifreader": {
+      "version": "4.1.0",
+      "resolved": "https://registry.npmjs.org/exifreader/-/exifreader-4.1.0.tgz",
+      "integrity": "sha512-LzTW96ubaHRSWVD6bgANpZgWGHdtA/jsIdVjFVhDDN6k60wid8U6b3cIWSGTfRePjZlwvyt4nt12bIQ5ywUrBw==",
+      "hasInstallScript": true,
+      "optionalDependencies": {
+        "@xmldom/xmldom": "^0.7.5"
+      }
+    },
     "node_modules/exit": {
       "version": "0.1.2",
       "resolved": "https://registry.npmjs.org/exit/-/exit-0.1.2.tgz",
@@ -27179,6 +27211,12 @@
       "integrity": "sha512-7tFImggNeNBVMsn0vLrpn1H1uPrUBdnARPTpZoitY37ZrdJREzf7I16tMrlK3hen349gr1NYh8CmZQa7CTG6Aw==",
       "dev": true
     },
+    "@xmldom/xmldom": {
+      "version": "0.7.5",
+      "resolved": "https://registry.npmjs.org/@xmldom/xmldom/-/xmldom-0.7.5.tgz",
+      "integrity": "sha512-V3BIhmY36fXZ1OtVcI9W+FxQqxVLsPKcNjWigIaa81dLC9IolJl5Mt4Cvhmr0flUnjSpTdrbMTSbXqYqV5dT6A==",
+      "optional": true
+    },
     "abab": {
       "version": "2.0.5",
       "resolved": "https://registry.npmjs.org/abab/-/abab-2.0.5.tgz",
@@ -27767,6 +27805,7 @@
         "eslint-config-prettier": "^2.9.0",
         "eslint-plugin-prettier": "^2.6.2",
         "events": "^3.3.0",
+        "exifreader": "^4.1.0",
         "hed-validator": "^3.5.0",
         "husky": "^1.0.0-rc.13",
         "ignore": "^4.0.2",
@@ -27786,6 +27825,7 @@
         "stream-browserify": "^3.0.0",
         "sync-request": "6.0.0",
         "table": "^5.2.3",
+        "xml2js": "^0.4.23",
         "yaml": "^1.10.2",
         "yargs": "^16.2.0"
       },
@@ -27883,6 +27923,7 @@
     "bids-validator-web": {
       "version": "file:bids-validator-web",
       "requires": {
+        "@babel/runtime": "^7.16.7",
         "bootstrap": "^4.3.0",
         "bowser": "^1.0.0",
         "next": "^11.1.2",
@@ -27892,6 +27933,16 @@
         "react-bootstrap": "^1.0.0-beta.5",
         "react-dom": "^17.0.2",
         "sass": "^1.32.8"
+      },
+      "dependencies": {
+        "@babel/runtime": {
+          "version": "7.16.7",
+          "resolved": "https://registry.npmjs.org/@babel/runtime/-/runtime-7.16.7.tgz",
+          "integrity": "sha512-9E9FJowqAsytyOY6LG+1KuueckRL+aQW+mKvXRXnuFGyRAyepJPmEo9vgMfXUA6O9u3IeEdv9MAkppFcaQwogQ==",
+          "requires": {
+            "regenerator-runtime": "^0.13.4"
+          }
+        }
       }
     },
     "big.js": {
@@ -29895,6 +29946,14 @@
         "strip-final-newline": "^2.0.0"
       }
     },
+    "exifreader": {
+      "version": "4.1.0",
+      "resolved": "https://registry.npmjs.org/exifreader/-/exifreader-4.1.0.tgz",
+      "integrity": "sha512-LzTW96ubaHRSWVD6bgANpZgWGHdtA/jsIdVjFVhDDN6k60wid8U6b3cIWSGTfRePjZlwvyt4nt12bIQ5ywUrBw==",
+      "requires": {
+        "@xmldom/xmldom": "^0.7.5"
+      }
+    },
     "exit": {
       "version": "0.1.2",
       "resolved": "https://registry.npmjs.org/exit/-/exit-0.1.2.tgz",