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  <import namespace="http://www.xbrl.org/2009/role/negated" schemaLocation="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd"></import>
  <import namespace="http://www.xbrl.org/2009/role/net" schemaLocation="http://www.xbrl.org/lrr/role/net-2009-12-16.xsd"></import>
  <import namespace="http://fasb.org/us-gaap/2022" schemaLocation="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd"></import>
  <import namespace="http://fasb.org/srt/2022" schemaLocation="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd"></import>
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  <element id="pacb_ExercisePriceRangeFiveMember" name="ExercisePriceRangeFiveMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration"></element>
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  <element id="pacb_StockholdersEquityLineItems" name="StockholdersEquityLineItems" nillable="true" type="xbrli:stringItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration"></element>
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  <element id="pacb_TimeBasedRestrictedStockUnitsRsusMember" name="TimeBasedRestrictedStockUnitsRsusMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
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  <element id="pacb_IlluminaFcOpsCorpMember" name="IlluminaFcOpsCorpMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_UsGovernmentCorporationsAndAgenciesSecuritiesNotIncludedWithCashAndCashEquivalentsMember" name="UsGovernmentCorporationsAndAgenciesSecuritiesNotIncludedWithCashAndCashEquivalentsMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
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  <element id="pacb_CashCashEquivalentsAndInvestmentsMember" name="CashCashEquivalentsAndInvestmentsMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
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  <element id="pacb_ConsumableMember" name="ConsumableMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_ContractWithCustomerLiabilityNoncurrentRecognitionPeriod" name="ContractWithCustomerLiabilityNoncurrentRecognitionPeriod" nillable="true" type="xbrli:durationItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_MergerAgreementContinuationAdvancesRepayableMinimumCompanyMustRaiseInEquityOrDebtFinancingInSingleTransaction" name="MergerAgreementContinuationAdvancesRepayableMinimumCompanyMustRaiseInEquityOrDebtFinancingInSingleTransaction" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="credit"></element>
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  <element id="pacb_MergerTermination" name="MergerTermination" nillable="true" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
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  <element id="pacb_EquityIncentivePlan2020Member" name="EquityIncentivePlan2020Member" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_FinancialInstrumentsTable" name="FinancialInstrumentsTable" nillable="true" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" abstract="true" xbrli:periodType="duration"></element>
  <element id="pacb_FinancialInstrumentsLineItems" name="FinancialInstrumentsLineItems" nillable="true" type="xbrli:stringItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration"></element>
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  <element id="pacb_InducementEquityIncentivePlan2020Member" name="InducementEquityIncentivePlan2020Member" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_ScheduleOfEarningsPerShareTable" name="ScheduleOfEarningsPerShareTable" nillable="true" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" abstract="true" xbrli:periodType="duration"></element>
  <element id="pacb_ScheduleOfEarningsPerShareLineItems" name="ScheduleOfEarningsPerShareLineItems" nillable="true" type="xbrli:stringItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration"></element>
  <element id="pacb_DebtInstrumentConversionRateSharesIssuedPerStatedPrincipalAmount" name="DebtInstrumentConversionRateSharesIssuedPerStatedPrincipalAmount" nillable="true" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_DebtInstrumentStatedPrincipalAmountForConversionRate" name="DebtInstrumentStatedPrincipalAmountForConversionRate" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="credit"></element>
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  <element id="pacb_SecurityDepositMember" name="SecurityDepositMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_InvitaeCorporationMember" name="InvitaeCorporationMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_ConvertibleSeniorNotesMember" name="ConvertibleSeniorNotesMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_DebtInstrumentAdditionalInterestInEventOfDefault" name="DebtInstrumentAdditionalInterestInEventOfDefault" nillable="true" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_EachDayDuringFirst180DaysMember" name="EachDayDuringFirst180DaysMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_OneHundredAndEightyFirstDayTo360thDayMember" name="OneHundredAndEightyFirstDayTo360thDayMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_ScheduleOfInterestExpenseTableTextBlock" name="ScheduleOfInterestExpenseTableTextBlock" nillable="true" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_ContractualInterestExpense" name="ContractualInterestExpense" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="debit"></element>
  <element id="pacb_ScheduleOfDevelopmentAndCommercializationAgreementTransactionsTable" name="ScheduleOfDevelopmentAndCommercializationAgreementTransactionsTable" nillable="true" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" abstract="true" xbrli:periodType="duration"></element>
  <element id="pacb_DevelopmentAndCommercializationAgreementTransactionsLineItems" name="DevelopmentAndCommercializationAgreementTransactionsLineItems" nillable="true" type="xbrli:stringItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration"></element>
  <element id="pacb_ProceedsFromRepaymentsOfContractTermination" name="ProceedsFromRepaymentsOfContractTermination" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="debit"></element>
  <element id="pacb_DebtInstrumentRedemptionPricePercentageOfConversionPrice" name="DebtInstrumentRedemptionPricePercentageOfConversionPrice" nillable="true" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_DebtInstrumentRedemptionPriceTradingDays" name="DebtInstrumentRedemptionPriceTradingDays" nillable="true" type="xbrli:durationItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_DebtInstrumentRedemptionPriceConsecutiveTradingDays" name="DebtInstrumentRedemptionPriceConsecutiveTradingDays" nillable="true" type="xbrli:durationItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_AnnualDecreaseInLongTermRestrictedCash" name="AnnualDecreaseInLongTermRestrictedCash" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="debit"></element>
  <element id="pacb_StockIssuedDuringPeriodInPrivatePlacementNetOfIssuanceCosts" name="StockIssuedDuringPeriodInPrivatePlacementNetOfIssuanceCosts" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="credit"></element>
  <element id="pacb_IssuanceOfCommonStockInPrivatePlacementNetOfIssuanceCostsShares" name="IssuanceOfCommonStockInPrivatePlacementNetOfIssuanceCostsShares" nillable="true" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_OmniomeIncMember" name="OmniomeIncMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_CirculomicsIncMember" name="CirculomicsIncMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_StockBasedCompensationExpenseExcludedFromConsiderationTransferred" name="StockBasedCompensationExpenseExcludedFromConsiderationTransferred" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="debit"></element>
  <element id="pacb_BusinessCombinationRecognizedIdentifiableAssetsOperatingLeaseRightOfUseAssetsNetAcquiredAndLiabilitiesAssumedOperatingLeaseRightOfUseAssetsNet" name="BusinessCombinationRecognizedIdentifiableAssetsOperatingLeaseRightOfUseAssetsNetAcquiredAndLiabilitiesAssumedOperatingLeaseRightOfUseAssetsNet" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="debit"></element>
  <element id="pacb_AchievementOfMilestoneMember" name="AchievementOfMilestoneMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_OmniomeStockAwardsRelatedToAcquisitionMember" name="OmniomeStockAwardsRelatedToAcquisitionMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_IncomeTaxBenefitFromReductionInDeferredTaxAssetsValuationAllowance" name="IncomeTaxBenefitFromReductionInDeferredTaxAssetsValuationAllowance" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="credit"></element>
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  <element id="pacb_ExercisePriceRangeAcqusitionTwoMember" name="ExercisePriceRangeAcqusitionTwoMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_MergerRelatedExpensesStockSettledMember" name="MergerRelatedExpensesStockSettledMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_MergerRelatedExpensesMilestoneMember" name="MergerRelatedExpensesMilestoneMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
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  <element id="pacb_MergerRelatedExpensesCashSettledMember" name="MergerRelatedExpensesCashSettledMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_PercentageOfFeeToPrepayDebt" name="PercentageOfFeeToPrepayDebt" nillable="true" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_AmortizationOfIntangibleAssetsAndResearchDevelopmentExpense" name="AmortizationOfIntangibleAssetsAndResearchDevelopmentExpense" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="debit"></element>
  <element id="pacb_ScheduleOfBusinessAcquisitionsByAcquisitionConsiderationTranferredTableTextBlock" name="ScheduleOfBusinessAcquisitionsByAcquisitionConsiderationTranferredTableTextBlock" nillable="true" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
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  <element id="pacb_ProceedsFromIssuanceOfCommonStockUnderEquityOfferingsNetOfIssuanceCosts" name="ProceedsFromIssuanceOfCommonStockUnderEquityOfferingsNetOfIssuanceCosts" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="debit"></element>
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  <element id="pacb_ChangesInEstimatedFairValueOfContingentConsiderationLiabilitiesTableTextBlock" name="ChangesInEstimatedFairValueOfContingentConsiderationLiabilitiesTableTextBlock" nillable="true" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
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  <element id="pacb_TimeBasedStockOptionMember" name="TimeBasedStockOptionMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_TenPercentOrGreaterBalanceAccountsReceivableMember" name="TenPercentOrGreaterBalanceAccountsReceivableMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_SharesIssuableUponConversionOfConvertibleSeniorNotesMember" name="SharesIssuableUponConversionOfConvertibleSeniorNotesMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_OptionsToPurchaseCommonStockMember" name="OptionsToPurchaseCommonStockMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_AdditionalRestrictedCashAndCashEquivalentsNoncurrent" name="AdditionalRestrictedCashAndCashEquivalentsNoncurrent" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="debit"></element>
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  <element id="pacb_TimeBasedAndPerformanceBasedOptionsMember" name="TimeBasedAndPerformanceBasedOptionsMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_SingleCustomerWith10OrGreaterMember" name="SingleCustomerWith10OrGreaterMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_NumberOfCustomers" name="NumberOfCustomers" nillable="true" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_ContingentConsiderationLiabilityMember" name="ContingentConsiderationLiabilityMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
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  <element id="pacb_PercentageOfOutstandingSharesOfCommonToBeIssuedInMerger" name="PercentageOfOutstandingSharesOfCommonToBeIssuedInMerger" nillable="true" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_AmendedAndRestatedAgreementMember" name="AmendedAndRestatedAgreementMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_ShareBasedPaymentArrangementOptionExercisePriceRangeCanceledLowerRangeLimit" name="ShareBasedPaymentArrangementOptionExercisePriceRangeCanceledLowerRangeLimit" nillable="true" type="dtr-types:perShareItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
  <element id="pacb_ShareBasedPaymentArrangementOptionExercisePriceRangeCanceledUpperRangeLimit" name="ShareBasedPaymentArrangementOptionExercisePriceRangeCanceledUpperRangeLimit" nillable="true" type="dtr-types:perShareItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element>
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  <element id="pacb_StockIssuedDuringPeriodSharesInPrivatePlacementNetOfIssuanceCosts" name="StockIssuedDuringPeriodSharesInPrivatePlacementNetOfIssuanceCosts" nillable="true" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration"></element></schema>
